Bikramjit Basu

Biomaterials
Science and
Implants
Status, Challenges and Recommendations
Biomaterials Science and Implants
Bikramjit Basu

Biomaterials Science
and Implants
Status, Challenges and Recommendations

123
Bikramjit Basu
Materials Research Center and BioSystems
Science and Engineering
Indian Institute of Science Bangalore
Bengaluru, Karnataka, India

ISBN 978-981-15-6917-3 ISBN 978-981-15-6918-0 (eBook)

https://doi.org/10.1007/978-981-15-6918-0
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Foreword by The President, Indian National
Science Academy

The Indian National Science Academy has assigned itself an important mandate of
informing society, stakeholders and policymakers on various issues of science that
are of relevance to society. This is being carried out through comprehensive reports
and books, on the status of specific subjects through a narrative of evidence-based
understanding of scientific research at the cutting edge. The literature is presented in
a simple to understand manner and deals with aspects of education, research, and
future possibilities, future challenges and suggestions for policies to take India
forward. These reports project the needs of India during the coming two to three
decades.
This monograph on Biomaterials Science and Implants by Prof. Bikramjit Basu
presents one such effort. The book deals with a complimentary subject of bioma-
terials, with the present science and education scenario, traces the historical
developments, summarises the present status and gazes in to the future. It discusses
various realms of this science that he terms as immigration science, that
derives/depends on contributions from a variety of disciplines, such as material
sciences, especially the synthetic hybrid materials, biological sciences, health sci-
ences, toxicological research besides biomechanics and manufacturing sciences.
Various chapters of the monograph deal with (a) important developments, espe-
cially in the field of medical implants, the need to augment teaching in this disci-
pline and the future possibilities, given that biomaterials will be an important
economic driver for the country; (b) current research scenarios and technical
challenges; and (c) the need for future research. The monograph is well-illustrated
with data and figures to help the reader. This monograph was reviewed by two
experts and we thank them for their help in providing timely and incisive reviews.
Both the experts commended this monograph.
On behalf of INSA, I am pleased to present this monograph to the public and
policymakers, including the scientific fraternity, and I am sure it will eminently
serve the purpose, it was meant for. I would like to place on record our appreci-
ations for Prof. M. S. Valiathan to write a Foreword for this monograph. His doing
so, speaks volumes on the quality of science being presented by the author.
I compliment and congratulate Prof. Basu for his hard work. I sincerely hope that

v
vi Foreword by The President, Indian National Science Academy

this book will enthuse newer communities to join hands to develop major research
initiatives in this important area of biomaterials and bioengineering and create
nationwide traction.
I thank Prof. A. K. Singhvi, Vice President, INSA, for his active role in bringing
this book to fruition. I also would like to place on record my appreciation for Prof.
Gadadhar Misra for coordinating the publication of this book with M/s Springer
Nature India. This is the first book being published and coproduced by M/s
Springer Nature.

Ajay K. Sood
FRS, President
Indian National Science Academy
New Delhi, India
Foreword by M. S. Valiathan

In the last couple of decades, the field of biomaterials science and tissue engineering
is at the frontier of research and innovation, considering the number of scientific
discoveries and their potential impact in treating human diseases. Overall, this book
emphasises the enormous need for the supply of regenerated organs and tissues, as
the spontaneous capacity for regeneration is limited in the human body. To sub-
stantiate the relevance for human healthcare, degenerative and inflammatory
problems of bone and joints affect millions of people worldwide.
In order to address biomedically relevant challenges in orthopaedics as well as
neural and cardiovascular diseases, researchers must blend the fundamental con-
cepts of engineering sciences (materials science), basic sciences (chemistry and
physics) and biological sciences (cell and molecular biology) to engineer synthetic
tissue replacements and develop novel healing strategies. Such an interdisciplinary
research approach requires understanding across the boundary of remotely linked
scientific disciplines. Researchers can develop innovative ideas, as well as under-
stand the language of this important research area of societal relevance. In most
significant terms, this monograph closes with the author's recommendations for the
policymakers, science administrators and lawmakers to facilitate the growth of this
field in near future and long term.
I am convinced that this important monograph, of considerable relevance to
India, should inspire many active researchers as well as young researchers, to think
laterally, while blending sufficient knowledge of biological systems with engi-
neering sciences to develop biomedical materials. The accelerated growth in the
fields of biomaterials and biomedical engineering, when most, if not all, the rec-
ommendations are translated to reality, is expected to facilitate affordable, yet
high-quality healthcare for millions of Indians and citizens of other countries
globally. To accompany the advances, the right regulatory and legislatory changes

vii
viii Foreword by M. S. Valiathan

are required. I personally find this much-needed monograph timely and immensely
valuable for the interdisciplinary scientific community pursuing the field of bio-
materials and biomedical engineering.

Manipal, India M. S. Valiathan

October 2019 Ch.M., FRCS, FRCS(C), FRCP, D.Sc (h.c)
National Research Professor
Padma Vibhushan Awardee (2005)
Former Vice-Chancellor
Manipal University
Former President, Indian National Science
Academy
Former Director
Sree Chitra Tirunal Institute for Medical
Sciences and Technology
Thiruvananthapuram
Preface

Who, What, When, Where, Why and How

We are now in an era of interdisciplinary research, as a matter of necessity and also

of knowledge: in themes and topics, in perspectives and problem-definition, in
execution and evaluation. The field of biomaterials science is one such interdisci-
plinary research field. In this monograph, I have made extensive efforts to sketch
the Indian landscape at work in this socially important area of scientific research,
against the international backdrop. The main aim of this monograph is to stimulate
actions by a wide variety of stakeholders who read this report.
I am a materials scientist by academic training and a biomaterials scientist by
calling. At the initial phase of my career in biomaterials, I was aware of the
challenges involved in entering an unexplored interdisciplinary domain that pro-
mises to have a dramatic impact on critical real-world problems in the next decades.
I can still recollect the uphill battle when I started pursuing science-to-implant
innovation, involving clinicians and companies. Against this backdrop, I have
summarised the major challenges and opportunities in the field, for young as well as
established researchers in the field.
The Indian medical device market is dominated by foreign companies, with over
70% of demands being met through imports. Currently, approximately one million
patients need prostheses and implants every year, and India imports a big slice,
worth Rs. 7000 crore a year (approximately $1 billion USD). Alongside, bioma-
terials research internationally is progressing in leaps and bounds at several insti-
tutions of repute. In this context, I have penned down a set of recommendations,
which I believe should be considered as priority recommendations by all stake-
holders for building the research ecosystem of India’s tomorrow.

ix
x Preface

The Roadmap: Engaging Key Stakeholders

When we define the progress of a particular field, we are required to think of its
issues, challenges and bottlenecks. However, equally important is attempting to
solve these problems, brainstorm recommendations and action plans.
It is high time that a monograph on the national status of research in biomaterials
is presented. It is time for real inquiry into select global institutes of importance, for
highlighting challenges and, most of all, issuing actionable recommendations that
will expedite inventions from the bench to the bedside. There is no one road-map
that fits all ecosystems, and therefore, this monograph is best used as a means to
stimulate thinking in the right direction. The process of building dynamic inno-
vation ecosystems involves not only working out the details, but also mastering the
art of motivation, organisation and negotiation. It is hoped that this text will be
well-received by science administrators, policymakers, legislators and citizens, in
the context of developing countries, taking India as an example.
The monograph, however, also contains valuable information for anyone who is
interested in learning about the current issues and trends, gaps and synergies, in
biomaterials sciences and bioengineering. It should also be useful for those inter-
ested in knowing about the status of major national and international research
centres. The list of global institutes of importance presented here is not exhaustive
and I acknowledge that there are others that have not been highlighted here that are
also of high calibre.
In particular, this monograph is visualised as a strategic roadmap to balance the
needs of the following stakeholders, towards building the regulatory framework:
1. Science administrators
2. Policymakers and legislators
3. Research coordinators, incubators and funding officers
4. Scientists and young researchers, including Ph.D. students, in Academia
5. MSMEs and industry
6. Clinicians

The Guide: Navigating the Monograph

Readers are encouraged to navigate this report by first considering the Contents,
what the purport of each chapter is and then, identifying the sections that are of
greatest importance to the reader, based on their expertise, interests and organisa-
tion. The first four chapters are intended to provide a foundational discussion of the
field and the status of ongoing research, nationally and globally. Subsequent to this,
the fifth chapter, “A Challenging Frontier”, is intended to provide the reader with an
overview of the key challenges in the field. The sixth chapter, “Recommendations”,
is intended to stimulate the minds of the readers on key recommendations and the
accompanying timeline-specific action plans.
Preface xi

Actionable Takeaways: Determining What Actions to Take

The main aim of this monograph is to stimulate actions by a wide variety of

stakeholders who read this report. The actions should be focussed on contributing to
the development of the biomaterials and bioengineering fields. This can be in the
form of actions related to specific challenges and recommendations presented here.
The list, however, is not exhaustive, and the reader is welcome to think of further
challenges and recommendations that can be addressed. I am hopeful that the
monograph will trigger new conversations and discussions among peer groups
towards a more detailed action plan. It is strongly recommended that the policy-
makers and lawmakers make note of actions based on the selected sections of
relevance, in the fifth and sixth chapters. I am confident that the insights gained
from this monograph, and the actions that it will stimulate, will enable a more
robust and congruent ecosystem for biomaterials science and implants. All the
views expressed in this monograph by the author are intended solely for the purpose
of discussion, and are not intended to offend any sentiments of any individual,
research group or other stakeholders in the biomaterial implants ecosystem. The
readers are welcome to share their comments or feedback with the author.

A Note of Thanks

Many challenges and recommendations, summarised in this book, are the reflection
of my understanding gained during the significant interactions with numerous
collaborators from academia, national laboratories, medical institutions and industry
as well as young researchers, in India and abroad. I have acknowledged this in a
separate list, which also contains a number of science administrators or policy-
makers. I am grateful to all of them for their time and useful suggestions. I thank my
current and former students, including Nitu Bhaskar, Srimanta Barui, Subhadip
Basu, Swati Sharma, Vidushi Sharma, Ranjith Kumar P., Asish Kumar Panda,
Gowtham N. H., Soumitra Das, Deepa Mishra, Sulob Roy Chowdhury, Indu
Bajpai, Subhadip Bodhak, Yashoda Chandorkar, Subhomoy Chatterjee,
Ashutosh K. Dubey, Shilpee Jain, Ravikumar K., Alok Kumar, Prafulla K. Mallik,
Atiar Molla, Shekhar Nath, Shibayan Roy, Naresh Saha, Debasish Sarkar,
B. Sunilkumar, Greeshma T., Garima Tripathi and Raghunandan Ummethala.
I deeply acknowledge the support of Dr. Nandita Keshavan, Dr. Damayanti Datta,
Mrs. Prerana S., Ms. Sheetal Chowdhury, Ms. Titash Mukherjee, Ms. Rea Johl and
Mr. Nihal Kottan in preparing this monograph. I also appreciate the comments and
constructive suggestions of the reviewers of this book. Finally, I am grateful to my
wife, Pritha Basu, and son, Prithvijit Basu, as well as other family members for their
xii Preface

unconditional support during writing this monograph. I am also indebted to my

parents, Manoj Mohan Basu (father) and Chitra Basu (mother) for their constant
encouragement and inspiration throughout my life. I truly acknowledge the finan-
cial support received from the Indian National Science Academy, Scheme for
Promotion of Academic and Research Collaboration (SPARC) and Indian Institute
of Science, Bangalore, during the writing of this monograph.

Bikramjit Basu
Ph.D., CEng., FACerS, FAMS, FAIMBE, FNAE, FNASc, FAScT, FBAO
Professor
Materials Research Center and BioSystems
Science and Engineering
Indian Institute of Science, Bangalore
Bengaluru, Karnataka, India
Honorary Professor
University of Manchester
Manchester, UK
Acknowledgements

List of Scientists from Academia and National Laboratories

Consulted

Kantesh Balani, Indian Institute of Technology Kanpur, India

Rinti Banerjee, Indian Institute of Technology Bombay, India
Dipankar Banerjee, Indian Institute of Science, Bangalore, India
Ananya Barui, Indian Institute of Engineering Science and Technology, Shibpur,
India
Naresh Bhatnagar, Indian Institute of Technology Delhi, India
Aldo Boccaccini, Institute of Biomaterials, Erlangen, Germany
K. Muraleedharan, CSIR-CGCRI, Kolkata, India
Vamsi Krishna Balla, CSIR-CGCRI, Kolkata, India
Subhadip Bodhak, CSIR-CGCRI, Kolkata, India
Biswanath Kundu, CSIR-CGCRI, Kolkata, India
Marc Bohner, RMS Foundation, Bettlach, Switzerland
Rajendra K. Bordia, Clemson University, USA
Annabel Braem, Katholieke Universiteit Leuven, Belgium
Sarah Cartmell, University of Manchester, UK
Kaushik Chatterjee, Indian Institute of Science, Bangalore, India
Jérôme Chevalier, Institut National des Sciences Appliquées (INSA), Lyon, France
Pallab Dutta, Indian Institute of Engineering Science and Technology, Shibpur,
India
Mitun Das, CSIR-CGCRI, Kolkata, India
Brian Derby, University of Manchester, UK
Alok Dhawan, CSIR-Indian Institute of Toxicology Research, Lucknow, India
Santanu Dhara, Indian Institute of Technology Kharagpur, India
Christophe Drouet, Centre Inter-universitaire de Recherche et d’Ingénierie des
Matériaux, Toulouse, France
Ashutosh K. Dubey, Indian Institute of Technology (BHU), Varanasi, India

xiii
xiv Acknowledgements

Michael Gelinsky, Technische Universität Dresden, Germany

Liesbet Geris, Katholieke Universiteit Leuven, Belgium
Sourabh Ghosh, Indian Institute of Technology Delhi, India
Swati Haldar, Indian Institute of Technology Roorkee, India
Julian Jones, Imperial College London, UK
Surya Kalidindi, Georgia Institute of Technology, USA
Subramani Kanagaraj, Indian Institute of Technology Guwahati, India
Manoj Komath, Sree Chitra Tirunal Institute for Medical Sciences and Technology,
Thiruvananthapuram, India
Veena Koul, Indian Institute of Technology Delhi, India
Ashok Kumar, Indian Institute of Technology Kanpur, India
A. M. Kuthe, Visvesvaraya National Institute of Technology, Nagpur, India
Debrupa Lahiri, Indian Institute of Technology Roorkee, India
Cato Laurencin, University of Connecticut, USA
Anne Leriche, Université Polytechnique Hauts-de-France, Valenciennes, France
H. S. Maiti, Former Director, CSIR-Central Glass and Ceramic Research Institute,
Kolkata, India
Biman B. Mandal, Indian Institute of Technology Guwahati, India
Saumen Mandal, National Institute of Technology Karnataka, Surathkal, India
Sujata Mohanty, All India Institute of Medical Sciences, New Delhi, India
Subha Narayan Rath, Indian Institute of Technology Hyderabad, India
Abhay Pandit, National University of Ireland, Galway, Ireland
Hardik Pandya, Indian Institute of Science, Bangalore, India
Jouni Partanen, Aalto University, Finland
Falguni Pati, Indian Institute of Technology Hyderabad, India
Yarlagadda Prasad, Queensland University of Technology, Australia
Seeram Ramakrishna, National University of Singapore, Singapore
B. Ravi, Indian Institute of Technology Bombay, India
Rui Reis, 3Bs’ Research Group, University of Minho, Braga, Portugal
Amit Roy Chowdhury, Indian Institute of Engineering Science and Technology,
Shibpur, India
Debashish Sarkar, National Institute of Technology, Rourkela, India
T. S. Sampathkumar, Indian Institute of Technology Madras, India
Jukka Seppälä, Aalto University, Finland
C. P. Sharma, Sree Chitra Tirunal Institute for Medical Sciences and Technology,
Thiruvananthapuram, India
D. D. Sarma, Indian Institute of Science, Bangalore, India
Molly Shoichet, University of Toronto, Canada
Carl G. Simon, Jr., National Institute of Standards & Technology (NIST),
Gaithersberg, MD, USA
Neetu Singh, Indian Institute of Technology Delhi, India
Simone Sprio, Istituto di Scienza e Tecnologia dei Materiali Ceramici (ISTEC),
Faenza, Italy
Acknowledgements xv

N. Ravi Sundaresan, Indian Institute of Science, Bangalore, India

Anna Tampieri, Istituto di Scienza e Tecnologia dei Materiali Ceramici (ISTEC),
Faenza, Italy
H. K. Varma, Sree Chitra Tirunal Institute for Medical Sciences and Technology,
Thiruvananthapuram, India

List of Clinicians Consulted

Aniruddh T. J., M. S. Ramaiah Memorial Hospital, Bangalore, India

Yogesh Chawla, Postgraduate Institute of Medical Education and Research,
Chandigarh, India
Amit. K. Dinda, All India Institute of Medical Sciences, New Delhi, India
Anil Mandhani, Medanta, the Medicity, Gurugram, India
Ivan Martin, University Hospital of Basel, Switzerland
K. V. Menon, Sparsh Hospital, Bangalore, India
B. V. S. Murthy, Ramaiah University of Applied Sciences, Bangalore, India
Sunil Nikose, Datta Meghe Institute of Medical Sciences, Wardha, India
Zahir Quaziuddin, Datta Meghe Institute of Medical Sciences, Wardha, India
C. Rex, Rex Hospital, Coimbatore, India
Vibha Shetty, Ramaiah University of Applied Sciences, Bangalore, India
Balendra Singh, King George’s Medical University, Lucknow, India
D. C. Sundaresh, Ramaiah University of Applied Sciences, Bangalore, India
Rajesh T. R., Sparsh Hospital, Bangalore, India
M. S. Valiathan, Manipal University, India
Ajit Yadav, Gleneagles Global Health City, Chennai, India

List of Science Administrators/Policymakers Consulted

Florent Bernard, European Commission, Brussels, Belgium

Kakali Dey Dasgupta, Department of Biotechnology, Government of India, New
Delhi, India
Katherine Freeman, Healthcare Technologies, Engineering and Physical Sciences
Research Council (EPSRC), UK
Kalaivani Ganesan, Department of Biotechnology, Government of India, New
Delhi, India
Priyankana Mukherjee, IKP Engineering, Design, and Entrepreneurship Network,
Bangalore, India
Gert Roebben, European Commission, Brussels, Belgium
xvi Acknowledgements

Alka Sharma, Department of Biotechnology, Government of India, New Delhi,

India
Ashutosh Sharma, Department of Science and Technology, Government of India,
New Delhi, India
Jitendar Sharma, Andhra Pradesh MedTech Zone, India
Soumya Swaminathan, World Health Organisation
Sandeep Verma, Science Engineering and Research Board, Government of India,
New Delhi

List of Industry Professionals Consulted

Rohan Aggarwal, Vidcare Innovations, Pune, India

S. K. Banerji, Orthotech, Gujarat, India
Debasish Bhattacharjee, TATA Steel Limited, India
Sudip Bose, TATA Steel Limited, India
M. Chandrashekharan, SMATEC b.v.b.a., Belgium
Aroop K. Dutta, Excel Matrix Biological Devices Pvt. Ltd., Hyderabad, India
Ranjna C. Dutta, Excel Matrix Biological Devices Pvt. Ltd., Hyderabad, India
Nilay Lakhkar, SynThera Biomedical, Pune, India
Subrata Mukherjee, TATA Steel Limited, India
Kamlesh Patel, Kaaryans Technical Ceramics, Gujarat, India
Kingshuk Poddar, TATA Steel Limited, India
Sabyasachi Roy, ANTS Ceramics, Vasai, India
Ravi Sarangapani, Biomedical Engineering Consultant, Pune, India
Mario van Wingerde, TATA Steel Limited, India

List of Institutions Consulted

Andhra Pradesh Med Tech Zone, Visakhapatnam, India

BETiC (Biomedical Engineering and Technology Incubation Centre), India
IKP Engineering, Design, and Entrepreneurship Network, Bangalore, India
Istituto di Scienza e Tecnologia dei Materiali Ceramici (ISTEC), Faenza, Italy
Kalam Institute of Health Technology, Visakhapatnam, India
PSG Institute of Advanced Studies, Coimbatore, India
Sree Chitra Tirunal Institute for Medical Sciences and Technology,
Thiruvananthapuram, India
Acknowledgements xvii

List of Funding Agencies

Department of Biotechnology, Government of India

Department of Science and Technology, Government of India
Indian National Academy of Engineering, Gurugram, India
Indian National Science Academy, New Delhi, India
Scheme for Promotion of Academic and Research Collaboration, Government of
India
Executive Summary

“Nothing is more powerful than an idea whose time has come”.

Do you know what hides in your hospital bills? Take a deep breath and prepare
to be surprised: 40% of the expenses are attributed to medical equipment, of which
about 70% come from high-tech diagnostic tests.
Medical devices single-handedly offset the healthcare cost impact. That is
because, nearly 80% of devices come from outside the country: the USA, Germany,
France, Singapore, China and the Netherlands. The dark side of the story is
well-known: one in every four households in India is pushed into debt every year
over healthcare costs. Not just Indians, consider the large number of patients who
come for treatment from the Middle East, Africa and neighbouring countries
(Bangladesh, Sri Lanka, Nepal, Bhutan, etc.).
The deficits of the current research ecosystem in India play a key role in this
chain of skyrocketing costs and unmet clinical needs. A key challenge for inno-
vation is the manufacturing of affordable biomedical devices without compromising
on quality. Made of metals and alloys, ceramics and carbons, polymers and com-
posites and other materials, biomaterials are used every day in surgery, in dental
applications and orthopaedics and drug delivery. Then, there are smart biomaterials,
a field that is developing at a very rapid pace, which can interact with biological
systems, directly influencing cell behaviour.
India has sent out tectonic ripples across the world with its mammoth healthcare
scheme for the under-privileged citizens. In line with the vision of affordable
medical costs, it is essential to develop a national roadmap for indigenous
high-performance biomedical implants and devices, in an accelerated manner. To
bring the benefits of cutting-edge science from the laboratory benchside to the
patient bedside, it is imperative to complete the full cycle of translational research.
For all persons involved in this field, from all sectors, it is the right time to think
about implementing engaging action plans that are tailored to the needs of the
times. In order to introduce the readers to the status of the field, the introductory
chapter discusses important concepts in the field, and the Appendix lists interna-
tionally approved definitions as well as details of the national meetings, which led
the author to conceive this text.

xix
xx Executive Summary

A major bottleneck is the poorly conceived regulatory framework in India. The

strategic road ahead lies in implementing robust national regulatory policy and
translational research programmes with strong involvement of clinicians and
industry, towards the discovery and deployment of new biomaterials and implants.
Furthermore, the author proposes the development of biomaterialomics (biomate-
rials with data science), which relies on a data-driven integrated understanding of
biocompatibility and elements of biomaterials development, while leveraging both
conventional and advanced manufacturing (e.g. 3D bioprinting).
The recommendations laid down in this monograph should help to establish
India as a global market leader for a new generation of bioimplants, whose pre-
dictive clinical performance would be closely tracked by “digital twins”. An out-
come of this strategic initiative would be realised in the creation of new
employment opportunities for skilled and semi-skilled Indians, together with the
education and training of next-generation researchers.
It is the author’s vision that such a text would not only encourage young
researchers to be passionate about understanding the current challenges, and those
of the end-user, but also inspiring them to form strong collaborations for adaptive
problem solving, thereby making significant contributions to the field. Also, this
monograph would be useful in honing the knowledge of those established in the
field by broadening their understanding on the research ecosystem in developed
nations and the national context. These topics are of greater importance towards
building an India of the future, where innovations can have a palpable impact, and
technological innovations meet the healthcare needs of society. Given the right
support, the key recommendations presented here can be highly transformative to
the field. “Nothing can stop an idea whose time has come”, Victor Hugo, the French
epic novelist, once wrote. We have proposed here the idea of the moment. An idea
that can carry forward both people’s wellbeing and the nation’s economy in its
energy and momentum.
Contents

1 Crossing the Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.1 Biomaterials Bloom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 The New Science . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.1 The Key Elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.2.2 Defining Biocompatibility . . . . . . . . . . . . . . . . . . . . . . . . 9
1.2.3 Structural Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.3 Stem Cells and Regenerative Engineering . . . . . . . . . . . . . . . . . 12
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial
Implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.4.1 Musculoskeletal Surgery and Orthopaedics . . . . . . . . . . . 15
1.4.2 Dental Restoration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.4.3 Neurosurgical Treatment . . . . . . . . . . . . . . . . . . . . . . . . 18
1.4.4 Cardiovascular Treatment . . . . . . . . . . . . . . . . . . . . . . . . 21
1.4.5 Urological Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
1.4.6 ENT Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
1.5 The Tailpiece . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2 Economic Impact, Healthcare Initiatives, and Research
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.1 Potential Economic Impact of Innovation . . . . . . . . . . . . . . . . . . 30
2.1.1 International Market . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.1.2 National Market . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.2 India’s Healthcare Initiatives and Translational Research
Facilitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... 39
2.2.1 Translational Research Institutes and Programmes ...... 40
2.2.2 Kalam Institute of Health Technology
and the Andhra Pradesh MedTech Zone . . . . . . . . . . . . . 42
2.2.3 NITI Aayog and the National Health Stack . . . . . . . . . . . 44
2.3 Education and Human Resources . . . . . . . . . . . . . . . . . . . . . . . . 46
2.3.1 Bioengineering Curriculum and Indian Academia . . . . . . 46
2.3.2 Medical Education and Research in India . . . . . . . . . . . . 47

xxi
xxii Contents

2.4 Funding Status and Opportunity . . . . . . . . . . . . . . . . . . . . . . . . 49

2.4.1 National Funding Schemes . . . . . . . . . . . . . . . . . . . . . . . 49
2.4.2 International Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
2.5 A Way Forward . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
3 Scientists at Work in India . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
3.1 At the Tipping Point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.2 All About Joints: Hips, Knees, and Spines . . . . . . . . . . . . . . . . . 61
3.3 Bones and Teeth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.4 Cartilage, Bone, Cardiac, and Skin Tissue Engineering . . . . . . . . 69
3.5 Eyes, Nerves, and Ears . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
3.6 Antibacterial Biomaterials to Combat Implant-Associated
Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73
3.7 Regenerative Engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 76
3.8 3D (Bio) Printing of Biomaterials, Tissues, and Organs . . . . . .. 78
3.9 National Institutes of Importance and Centres
of Excellence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 81
3.9.1 Sree Chitra Tirunal Institute for Medical Sciences
and Technology, Thiruvananthapuram . . . . . . . . . . . . . .. 81
3.9.2 School of International Biodesign, All India Institute
of Medical Sciences, New Delhi . . . . . . . . . . . . . . . . . .. 83
3.9.3 Biomedical Engineering and Technology Incubation
Centre (BETiC), IIT Bombay . . . . . . . . . . . . . . . . . . . .. 83
3.9.4 Multi-institutional National Research Programs . . . . . . .. 84
3.9.5 Multi-institutional International Translational Research
Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 85
3.10 Nota Bene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 86
3.11 A Path Ahead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 87
4 International Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89
4.1 Global Landscape of Biomaterials Research Consortia . . . . . . .. 91
4.1.1 Prometheus Group, at Katholieke Universiteit Leuven,
Belgium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 91
4.1.2 McGowan Institute for Regenerative Medicine,
University of Pittsburgh, USA . . . . . . . . . . . . . . . . . . .. 91
4.1.3 ‘Cúram - Centre for Research in Medical Devices’,
NUIG Galway, Ireland . . . . . . . . . . . . . . . . . . . . . . . . .. 92
4.1.4 Wyss Institute at Harvard University, USA . . . . . . . . . .. 93
4.1.5 Centre for Translational Bone, Joint, and Soft Tissue
Research, TU Dresden, Germany . . . . . . . . . . . . . . . . .. 93
4.1.6 Istituto di Scienza e Tecnologia dei Materiali Ceramici
(ISTEC), Faenza, Italy . . . . . . . . . . . . . . . . . . . . . . . . .. 94
4.1.7 3B’s Research Group, University of Minho, Braga,
Portugal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 96
Contents xxiii

4.1.8 National Institute of Standards & Technology (NIST),

Gaithersburg, MD, USA . . . . . . . . . . . . . . . . . . . . . . . .. 96
4.1.9 Wake Forest Institute for Regenerative Medicine,
Winston-Salem, North Carolina, USA . . . . . . . . . . . . . . . 97
4.2 Multi-institutional Research Initiatives and Training Centres . . . . 98
4.2.1 Henry Royce Institute, UK . . . . . . . . . . . . . . . . . . . . . . . 98
4.2.2 Matériaux pour la Santé (MatSan), France . . . . . . . . . . . . 99
4.2.3 Materials Assembly and Design Excellence in South
Carolina (MADE in SC), Clemson University, USA . . . . 100
4.2.4 ARC Training Centre for Innovative Bioengineering,
University of Sydney, Australia . . . . . . . . . . . . . . . . . . . 101
4.3 Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
5 A Challenging Frontier and Status of National Policies . . . . . . . . . . 103
5.1 Accelerating Regulatory Approval . . . . . . . . . . . . . . . . . . . . . . . 104
5.1.1 Current Status and Gaps in Medical Device
Certification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
5.1.2 Manufacturing-Related Regulations . . . . . . . . . . . . . . . . . 106
5.2 Strengthening Basic Research in Biomaterials Science . . . . . . . . 107
5.2.1 Development of Next-Generation Biomaterials . . . . . . . . 108
5.2.2 Biomaterials and 3D Bioprinting-Based Approaches
for Regenerative Engineering . . . . . . . . . . . . . . . . . . . . . 110
5.2.3 Multiscale Computational Analysis . . . . . . . . . . . . . . . . . 113
5.2.4 Data Science Driven Approach . . . . . . . . . . . . . . . . . . . . 115
5.3 Building Translational Research for Human Healthcare . . . . . . . . 117
5.4 Nourishing Industry Collaborations, Incubators,
and Start-Ups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
5.5 Addressing the Gaps in Medical Education and the Clinical
Research Ecosystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
5.5.1 Education and Training . . . . . . . . . . . . . . . . . . . . . . . . . 123
5.5.2 Clinical Research Ecosystem Development . . . . . . . . . . . 124
5.6 Harnessing the Benefits of Biomaterials for the
Country . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
5.7 Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
6 Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
6.1 The Translational Gap . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
6.1.1 Science at the Local . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
6.1.2 Regulatory Impasse . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
6.1.3 Steering Science and Technology . . . . . . . . . . . . . . . . . . 132
6.2 Priority Recommendations for Fostering Innovation and Growth
of Biomedical Materials and Implants . . . . . . . . . . . . . . . . . . . . 132
6.2.1 Implement National Regulatory Framework
to Streamline Accelerated Regulatory Approval
Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
xxiv Contents

6.2.2 Strengthen Basic Research in Biomaterials Sciences

for Accelerated Innovation of Next-Generation
Biomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
6.2.3 Build Up Clinical, Context-Driven, Translational
Research Toward Treatment of Human Diseases . . . . . . . 139
6.2.4 Nourish Industry Collaborations and Capabilities,
Grow and Sustain Incubators and Start-Ups . . . . . . . . . . . 143
6.2.5 Revamp Medical Education and the Clinical Research
Ecosystem, to Train and Collaborate with Clinicians . . . . 146
6.2.6 Introduce and Implement National Policies
and Action Plans to Harness Benefits of Biomaterials
for the Public . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
7 Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Appendix: Pedagogy and the Genesis of this Book . . . . . . . . . . . . . . . . . . 157

Appendix A: Defining Key Elements of Biomaterials Science . . . . . . . . . 159
Appendix B: Ethical and Safety Considerations . . . . . . . . . . . . . . . . . . . . 163
Appendix C: International Research Groups . . . . . . . . . . . . . . . . . . . . . . 167
Appendix D: Conferences and Workshops . . . . . . . . . . . . . . . . . . . . . . . . 173
Appendix E: Road-Mapping Meetings. . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Additional Reading and References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
About the Author

http://bikramjitbasu.in/
Professor Bikramjit Basu is currently a Professor at
the Materials Research Center and holds Associate
Faculty position at Center for Biosystems Science and
Engineering, Indian Institute of Science (IISc),
Bangalore. He is currently Visiting Professor at
University of Manchester, UK. After his undergraduate
and postgraduate degree in Metallurgical Engineering
from NIT Durgapur and IISc respectively, he earned his
PhD in the area of Engineering Ceramics at Katholieke
Universiteit Leuven, Belgium in March, 2001.
Following a brief post-doctoral stint at University of
California, Santa Barbara; he served as a faculty of
Indian Institute of Technology Kanpur during
2001-2011. He has taught in UK, Spain, Slovenia,
Belgium and Nepal. He has successfully led interna-
tional research programs with USA, UK and Germany.
Professor Basu has been pursuing challenging inter-
disciplinary research at the cross-road, where Materials
Science, Biological Science and Medicine meet. He has
aptly used the principles of Biomaterials Science and
Biomedical Engineering to develop next generation
implants and biomedical engineering solutions in an
effort to address unmet clinical needs for musculoskele-
tal, dental, neurosurgical and urological applications.
Over the years, he has created interactive and intensive
collaborations with a number of clinicians and
entrepreneurs to accelerate bench science-to-device
prototype development. Encompassing theoretical
predictions, computational analysis, experimental

xxv
xxvi About the Author

discovery and clinical translational research, his

research group has laid the foundation for intelligent
design of implants, 3D binderjet printing of biomate-
rials, science of biocompatibility and bioengineering
strategies, to advance the development of biomedical
implants, regenerative engineering and bioelectronic
medicine. He is currently leading India’s major trans-
lational Center of Excellence on biomaterials with an
interdisciplinary team of researchers from academia and
medical institutions and hospitals. He has published
over 300 peer-reviewed research papers in leading
journals (total citations * 11,000 and H-index: 56).
Many of his former students are currently thriving
research programs in IITs and NITs in India. He has
co-authored 9 books, including 7 textbooks on
Biomaterials, Tribology and Ceramics.
Prof. Basu’s contributions in Biomaterials Science
have been widely recognised. He received India’s most
coveted science and technology award, Shanti Swarup
Bhatnagar Prize in 2013. A Chartered Engineer of UK,
he is an elected Fellow of the International Academy of
Medical and Biological Engineering (2020),
International Union of Societies for Biomaterials
Science and Engineering (2020), Indian Academy of
Sciences (2020), American Ceramic Society (2019),
American Institute of Medical and Biological
Engineering (2017), Institute of Materials, Minerals &
Mining, UK (2017), National Academy of Medical
Sciences, India (2017), Indian National Academy of
Engineering (2015), Society for Biomaterials and
Artificial Organs (2014) and National Academy of
Sciences, India (2013). He is currently serving as
Advisor to TATA Steel New Materials Business and is
an Abdul Kalam National Innovation Fellow.
Abbreviations

3D Three-dimensional
3DP Three-dimensional printing
3DPL Three-dimensional plotting
3DPP Three-dimensional powder printing
AB-PMJAY Ayushman Bharat Pradhan Mantri Jan Arogya Yojana
AcE Accelerating Entrepreneurs
ADMI Association of Diagnostics Manufacturers of India
AERB Atomic Energy Regulatory Board
AI Artificial Intelligence
AIG Asian Institute of Gastroenterology
AIIMS All India Institute of Medical Sciences
AiMeD Association of Indian Medical Devices Industry
AIR Academic Innovation Research
AJRR American Joint Replacement Registry
AMCHAM American Chamber of Commerce in India
AMTZ Andhra Pradesh Med Tech Zone
APIs Application Programme Interfaces
ARC Australian Research Council
BARC Bhabha Atomic Research Centre
BCIL Biotechnology Consortium of India Limited
BCP Biphasic Calcium Phosphate
BETiC Biomedical Engineering and Technology Incubation Centre
BHU Banaras Hindu University
BIPP Biotechnology Industry Partnership Programme
BIRAC Biotechnology Industry Research Assistance Council
BIS Bureau of Indian Standards
BME Biomedical Engineering
BRICS Brazil, Russia, India, China and South Africa (Five major
emerging economies)
BRIT Board of Radiation and Isotope Technology

xxvii
xxviii Abbreviations

CAGR Compound Annual Growth Rate

CASPA Calcium-Sulfate-Phosphate Active Composition
CBE Cellular and Biochemical Engineering
CDSCO Central Drugs Standard Control Organisation
CE mark Certification mark for products within the European Economic
Area
CGCRI Central Glass and Ceramic Research Institute
CII Confederation of Indian Industry
CIPET Central Institute of Plastics Engineering & Technology
CLRI Central Leather Research Institute
CMC Christian Medical College
CMF Craniomaxillofacial
CRO Contract Research Organisation
CRS Contract Research Scheme
CSIR Council of Scientific and Industrial Research
CT Computerised tomography
DAE Department of Atomic Energy
DBT Department of Biotechnology
DCC Drugs Consultative Committee
DEITY Department of Electronics and Information Technology
DRDO Defence Research and Development Organisation
DST Department of Science and Technology
DTAB Drugs Technical Advisory Board
ECM Extracellular matrix
EDEN Engineering, Design and Entrepreneurship Network
EIR Entrepreneur-in-residence
EMC Electro-Magnetic Compatibility testing
EMI Electro-Magnetic Interference testing
ENT Ear Nose Throat
EPSRC Engineering and Physical Sciences Research Council
EXAFS X-ray Absorption Spectroscopy
FDA Food and Drug Administration
FICCI Federation of Indian Chambers and Commerce Industry
GATE Graduate Aptitude Test in Engineering
GCE Grand Challenges Exploration
GLP Good Laboratory Practice
GMP Good Manufacturing Practice
GYTI Gandhian Young Technological Innovation
HA Hydroxyapatite
HDPE High-Density Polyethylene
HTA Health Technology Assessment
IBSC Indian Biomedical Skill Certificate
ICME Integrated Computational Materials Engineering
ICMR Indian Council of Medical Research
ICSSR Indian Council for Social Science Research
Abbreviations xxix

IIEST Indian Institute of Engineering Science and Technology

IISc Indian Institute of Science
IISER Indian Institute of Science Education and Research
IIT Indian Institute of Technology
IKP Trust Innovation, Knowledge, Progress Trust
IMDRF International Medical Device Regulators Forum
IMPRINT IMPacting Research Innovation and Technology
IOP Intraocular Pressure
IP Intellectual Property
IPR Intellectual Property Rights
ISO International Organisation for Standardisation
ISTEC Istituto di Scienza e Tecnologia dei Materiali Ceramici
IVRI Indian Veterinary Research Institute
JIPMER Jawaharlal Institute of Postgraduate Medical Education
KIHT Kalam Institute of Health Technology
LSRB Life Science Research Board
MADE in SC Materials Assembly and Design Excellence in South Carolina
MCI Medical Council of India
MD Molecular Dynamics
MDA Medical Devices Authority
MDTAG Medical Devices Technical Advisory Group
MEDHA Medical Device Hackathon
MEDIC Medical Device Innovation Camp
MHRD Ministry for Human Resource Development
MIILI Make In India leadership Institute
ML Machine Learning
MOU Memorandum of Understanding
MRI Magnetic Resonance Imaging
MSCs Mesenchymal Stem Cells
MSMEs Micro, Small and Medium scale Enterprises
MSRUAS M. S. Ramaiah University of Applied Sciences
MTAI Medical Technology Association of India
MWCNT Multi-Walled Carbon Nanotubes
NATFOS National Frontiers of Science
NHS National Health Stack
NHSRC National Health Systems Resource Centre
NIB National Institute of Biologicals
NIH National Institutes of Health
NIPUN Non-regulatory Innovation Potential Utility and Novelty
Certificate
NIST National Institute of Standards & Technology
NIT National Institute of Technology
NML National Metallurgical Laboratory
NPPA National Pharmaceutical Pricing Authority
NSF National Science Foundation
xxx Abbreviations

NSTIF National Science, Technology & Innovation Foundation

PACE Promoting Academic Research Conversion to Enterprise
PANI Polyaniline
PCL Polycaprolactone
PCT Patent Cooperation Treaty
PDMS Polydimethylsiloxane
PFMEA Process Failure Mode Effects Analysis
PGA Polyglycolic Acid
PGIMER Postgraduate Institute of Medical Education and Research
PLA Polylactic Acid
PLGA-CNF Polylactic-Polyglycolic Acid-Carbon nanofibre
PM-RSSM Pradhan Mantri-Rashtriya Swasthya Suraksha Mission
PM-STIAC Prime Minister’s Science, Technology and Innovation-Advisory
Council
PSP Process-Structure-Property
PTH Parathyroid Hormone
PVA Polyvinyl Alcohol
PVDF-CNT Polyvinylidene Fluoride-Carbon Nanotube
QA Quality Assurance
QC Quality Control
QCI Quality Council of India
R&D Research and Development
RCT Randomised Controlled Trial
ROME Reorientation of Medical Education
SBIRI Small Business Innovation Research Initiative
SCTIMST Sree Chitra Tirunal Institute for Medical Sciences and Technology
SEARN South East Asia Regulatory Network
SEED Fund Sustainable Entrepreneurship and Enterprise Development Fund
SERB Science and Engineering Board
SF Silk Fibroin
SGPGI Sanjay Gandhi Postgraduate Institute of Medical Sciences
SIB School of International Biodesign
SIIHEI Start-up India Initiative for Higher Education Institutions
SME Small-to-Medium Enterprise
SPARC Scheme for Promotion of Academic and Research Collaboration
SPARSH Social Innovation programme for Products: Affordable and
Relevant to Societal Health
SRISTI Society for Research and Initiatives for Sustainable Technologies
and Institutions
SSSIHMS Sri Sathya Sai Institute of Higher Medical Sciences
STEM Science, Technology, Engineering and Mathematics
SUPRA Scientific and Useful Profound Research Advancement
TCP Tricalcium Phosphate
TCS TATA Consultancy Services
TERM Tissue Engineering and Regenerative Medicine
Abbreviations xxxi

THA Total Hip Arthroplasty

THR Total Hip Joint Replacement
THSTI Translational Health Science and Technology Institute
TIMed Technology Business Incubator for Medical Devices and
Biomaterials
TKR Total Knee Replacement
TMJ Temporomandibular Joint
TRL Technology Readiness Level
UAY Uchchatar Avishkar Yojna
UHMWPE Ultra-high Molecular Weight Polyethylene
USA United States of America
USD United States of America Dollar
WFIRM Wake Forest Institute for Regenerative Medicine
WHO World Health Organisation
ZTA Zirconia Toughened Alumina
Chapter 1
Crossing the Boundaries

Abstract The future of science lies in breaking the down barriers between fields to
solve global challenges of our time. ‘Interdisciplinarity’ is the mantra to solve the
grand global challenges that no single discipline can address on its own. Scientists
from various backgrounds are coming together to transcend the boundaries of their
respective disciplines. The most exciting research is happening at the intersections,
where various scientific disciplines meet. The field of biomaterials science is one of
the finest examples of a truly interdisciplinary research field. This chapter introduces
the readers to key definitions of the scientific terms that a non-specialist needs to
know, before appreciating the major developments that have taken place over the
last few decades. The relevance of this important interdisciplinary field of science is
illustrated by citing a few biomaterials-based solutions to treat human diseases.

© Springer Nature Singapore Pte Ltd. 2020 1

B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0_1
2 1 Crossing the Boundaries

1.1 Biomaterials Bloom

In the recent past, there has been significant attention to bridge the gap between
biology and engineering sciences. Consistent efforts have resulted in the conceptual
evolution of ‘bioengineering’ or ‘biomedical engineering’ or ‘clinical engineering’,
as a distinct discipline. Another example is biomaterials science, which bridges the
gap between materials science and biology (see Fig. 1.1). The readers can refer to a set
of definitions in Appendix A. If disciplines are related, then ‘crossing the boundary’
becomes a little easier, but it is more challenging, when they are disconnected.

Although biomaterials as a field, formally, came into existence only after the
Second World War, the development of this important class of materials has
been well documented throughout history, albeit any scientific assessment of
their biocompatibility.

The ancient Indian physician, Susruta of sixth-century BC, reported the use of
sutures made of human hair, flax, and hemp to close skin incisions in his treatise,
Suṡruta-samhitā. As far as the early evolution of biomaterials is concerned, the
Greek physician, Galen of Pergamum, has also described catgut sutures to close
large wounds in the first-century AD. Nacre from sea shells was used as a substitute
for teeth, while metals, such as gold and wrought iron, were used as dental implants
in the early ages. Such cases highlight the use of an implant or prosthesis to recover
the loss of an anatomical function.
As of 1829, Henry Levert of Alabama investigated 21 different types of metallic
sutures, with those made of platinum performing the best. Surgeons then became
more interested in metal screws and plates to fix bone defects. In 1886, Hansmann

Fig. 1.1 Biomaterials science: integrates concepts from multiple disciplines

1.1 Biomaterials Bloom 3

used plates and screws successfully for the first time in Germany. In 1881, Etienne-
Jules Marcy published the first design for an artificial heart. By 1926, a new formu-
lation of stainless steel 18-8 has been formulated, which helped to address the issue
of corrosion of iron and steel in the body. It took around 100 years before anything
similar would be implanted into a human patient. The first blood vessel replacement,
using parachute material, was reported in 1952. This was found by Arthur Zierold
in metallic suture experiments.
The field of biomaterials blossomed mainly after the Second World War due to the
large need of the soldiers, who sustained battlefield injuries. Polymethyl methacrylate
(PMMA) shards, that were accidentally lodged in the eyes of aviators, did not create
inflammation or an adverse tissue reaction. This inspired British ophthalmologist,
Sir Harold Ridley, to create early intraocular lenses out of polymethyl methacrylate.
Today, polydimethylsiloxane (PDMS) lenses are being used instead, and cataract-
associated blindness can be avoided with the use of PDMS lenses.
A fine example of the use of a biomaterial for the treatment of musculoskeletal
diseases is that of the total hip joint replacement (THR), which has evolved to become
one of the most successful surgeries, with over 3,00,000 surgeries being performed
annually worldwide. A retrospection of the history of development of THR prostheses
is proof of how judicious material choice can increase surgery success rates. While
early attempts using metals (such as stainless steel) failed due to material design-
related issues, the use of a Teflon™ acetabular cup by Sir John Charnley, a British
orthopaedic surgeon, marked the beginning of the modern age in orthopaedics in
1961.
High-density polyethylene and stainless steel are currently used for THR and
other orthopaedic applications. Ever since the first intraocular lens was discovered
by Sir Harold Ridley in 1949, research and development in biomedical materials has
grown exponentially with the advent of new materials, technological expertise, and
novel applications. One such landmark is that of the bioglass developed by Larry L.
Hench in the late 1960s.
In the 1960s to 1980s, many advances in the field of biomaterials were made
and new materials were being explored, such as silicone, Teflon™, hydrogels, and
bioglass. In 1982, the first artificial heart was placed in a patient as a temporary
measure, and the patient lived for 64 hours. Subsequently, the Jarvik-7 model was
permanently implanted into a human subject, who lived for 112 days. In 2006,
Anthony Atala at Wake Forest Institute for Regenerative Medicine, USA, grew and
implanted a tissue-engineered bladder in human patients.
By 2019, examples of successful translations of biomaterials research include
hip and knee implants, dental implants, artificial kidney, breast implants, vascular
grafts and stents, pacemakers, and heart valves, etc. The range of applications for
these biomedical devices and their widespread use are commensurate with their ever-
increasing numbers. Thus, it can be rightly stated that biomaterials have become an
integral part of our lives today. Figure 1.2 shows the anatomical areas in the human
skeletal system, wherein synthetic biomaterials can be used for repair/replacement of
the injured part. In most of these cases, the materials, employed originally, were off-
the-shelf materials, without considerable redesign and were developed primarily for
4 1 Crossing the Boundaries

Cochlear Implants
Dental Implants
Contact lenses
Shoulder prosthesis
Cardiovascular
Implants Pacemaker
Lumbar disc replacement

Prosthetic Acetabular socket

arthroplasty

Knee joint

Bone fixation

Fig. 1.2 The spectrum of clinical applications of biomaterials. (Adapted from Alijani et al. 2018)

non-biological applications. Their interaction with biological systems was not suffi-
ciently understood until four decades ago. To this end, researchers have made signifi-
cant efforts in the last two decades to create new materials with specific requirements
for particular biological applications.

1.2 The New Science

A biomaterial is ideally destined to favourably interact with the components of the

living system. The multi-cellular living organism has a highly structured, hierarchical
organization, with each level having progressively increasing structural complexity.
In order of increasing complexity, these levels are cell, tissue, organ, and organ
system, respectively. A cell is the smallest unit of a biological system containing
various cellular organelles. A tissue is a self-organised array of similar types of
cells performing a similar function. At the next level, organs are formed when the
identical types of tissues, having a common function, are grouped together. Various
organ systems work together to maintain the life of a living organism.
The functionally related organs constitute a higher level of organisation, known
as an organ system. Vertebrate animals have many organ systems. For instance, the
digestive system includes organs, such as the oesophagus, intestine, liver, and gall
1.2 The New Science 5

bladder. In the human body, several thousands of cells of different types with millions
of proteins co-exist together.

From a scientific standpoint, each cell type prefers to adhere, proliferate, or

differentiate (change of functionality) on a biomaterial with specific compo-
sition, in a manner dependent on elastic stiffness, surface energy/surface
wettability.

The difference in preference or sensitivity for various cell types towards different
substrates substantiates the fact that the biomaterial composition or surface properties
should be tailored for a specific biomedical application.
Let us use a conceptual tetrahedron to illustrate the new science of biomaterials
to fabricate human tissues and organs (Fig. 1.3). The traditional material science
tetrahedron emphasises the interrelation between the four main areas of a material:
processing, microstructure, properties, and performance. To illustrate the develop-
ment cycle of biomaterials, I have adapted the tetrahedron to encompass the key
aspects of this process, as shown in Fig.1.3. For biomaterials, two distinct manufac-
turing techniques are particularly relevant: first, additive manufacturing (for instance,
3D printing, 3D bioprinting, 3D plotting, etc.), that has positively influenced fabri-
cation of patient-specific implants; second, porous scaffold manufacturing tech-
niques (e.g. salt leaching, and gel casting) that are integrated with biological cells
or molecules for regenerative medicine applications. The requirement of having
porosity in materials for specific biomedical applications (e.g. tissue engineering)
necessitates one to use a specific set of processing routes.
Concerning structure, the bulk microstructure and more importantly, surface, are
extremely significant in the context of interaction with biological systems. In partic-
ular, grain size or phase assemblage of a material in bulk determine many macroscale

Fig. 1.3 Schematic illustration of the Biomaterials Science Tetrahedron, a conceptual framework
used to take laboratory-scale research to patient’s bedside in clinic
6 1 Crossing the Boundaries

properties, like strength, toughness, etc. The surface topography, i.e. roughness or
presence of specific patterns, guides the way in which the cells will function on a
material surface. As part of the bulk structure, 3D porous architecture is particularly
important in the context of bone tissue engineering. The fine scale characterisation,
in terms of pore size distribution and interconnectivity in 3D space, requires one to
use specific characterisation tools, e.g. micro-computed tomography, which are not
widely used for various structural or functional materials. Similarly, reproducing the
3D architecture of the extracellular matrix is very crucial for scaffolds in soft tissue
regeneration.

In the context of properties, the bulk strength or toughness, and more impor-
tantly, elastic modulus, of an implantable biomaterial play an important role
in the biomechanical compatibility of a material in an osseous system.

In addition, the biocompatibility is to be sufficiently and ethically characterised

using a host of biochemical assays, and molecular biology techniques, etc. This
makes the field of biomaterials distinct from other fields of materials science. This
latter aspect requires the researchers to develop an appropriate level of understanding
of biological systems (cell, protein, bacteria, blood, etc.) and also to adopt techniques
of remotely linked disciplines, e.g. biological sciences.
The performance of an in vitro-tested biomaterial is to be assessed in pre-clinical
studies pre-approved by the ethical committee of the institute, involving experi-
mental animals. The selection of animal model, defect type, as well as study duration
or follow-up evaluation, depend on the specific biomedical application of a mate-
rial. Such studies also involve expertise from veterinary surgeons, toxicologists,
histopathologists, etc. The results of such studies provide scientific understanding of
tissue-material interaction. Once a material is proven to be biocompatible in animal
studies, the performance can be assessed in human clinical trials. It should be empha-
sised that clinical studies require even stricter approvals from institutional and/or
national ethical committees.

Once the outcome measures, over post-surgical periods in human subjects are
found to be clinically acceptable, a biomaterial implant or scaffold can be
commercialised for use in humans.

The above discussion certainly indicates an interactive and longer product devel-
opment cycle for biomaterials, when compared to those of other non-biomedical
materials. It also emphasises the need to adopt a different skillset or approach to estab-
lish processing-structure–property-performance correlation in the case of bioma-
terials, which is unique in nature. The interaction among several remotely linked
domains of expertise makes the field interesting and challenging (see Fig. 1.1).
Therefore, biomaterials science encompasses a multidisciplinary approach: from
engineering to biological to medical sciences (see Figs. 1.1 and 1.4).
1.2 The New Science 7

Biomaterials
Interactions Science

Implantable Living Structure-Composition-

biomaterials system Function Relationships

Engineering/ Medical/
Biological sciences
Foundational
Physical sciences
Sciences

Fig. 1.4 Concept triangle to describe the field of biomaterials science (Adapted from: Biomaterials
Science and Tissue Engineering: Principles and Methods, Cambridge University Press, 2017)

The students from non-biological sciences always seek to find the answer as
to how far, or to what extent, they will need to learn or understand the core of
the biological sciences discipline. While the fundamentals of engineering ideas can
be translated to fabricate and characterise synthetic materials, an understanding of
biological sciences is necessary to analyse the interaction of proteins, cells, bacteria,
and blood with synthetic biomaterials.

The biocompatibility is studied both in vitro (laboratory-scale experiments in

glassware or in culture/growth medium) or in vivo (study conducted in whole
organism, i.e. animal models).

An integrated understanding of cells/tissue interaction with a biomaterial consti-

tutes the central theme of the field of biomaterials science. Also, the interaction
between these disciplines makes biomaterials science a truly interdisciplinary field
of research (see Fig. 1.4). The discussion in the previous sections indicates that
although biomaterials science is a relatively young field, it has made significant
impact on human society.

1.2.1 The Key Elements

A biomedical material, or biomaterial, possesses many unique properties that allow it

to interact with living systems: proteins, cells and bacteria (see Fig. 1.4). Many defi-
nitions have been proposed over the years for the terms ‘biomaterial’ and ‘biocom-
patibility’. To begin with, biomaterials have been defined as natural or manmade
materials that can interface with biological systems, to evaluate, treat, augment, or
8 1 Crossing the Boundaries

replace tissues, organs or functions of the body. When these materials display univer-
sally ‘good’ or harmonious behaviour in contact with tissues, evoking a minimal
biological response; they are considered to have good biocompatibility. According
to another definition, biomaterial is a term used to indicate materials that constitute
parts of medical implants, devices, and disposables utilised in medicine, surgery,
dentistry, and the veterinary field, as well as in every aspect of patient healthcare. A
more formal definition is provided in Appendix A.
The materials used for biomedical applications can be broadly classified as
metallic (stainless steels, titanium and its alloys, cobalt–chrome alloys, etc.),
ceramic (calcium phosphates, alumina, zirconia, glass-ceramics, etc.), and poly-
meric (polyethylenes, PMMA, nylon, etc.). There are also some naturally occurring
materials, such as fibrin, collagen, hyaluronic acid, and silk that are being used for
biomedical applications.

It is important that a biomaterial must integrate or interact, in a clinically

acceptable manner, with the components of the living system.

At this point, it is necessary to highlight how the concepts of biological sciences

are adapted to biomaterials science. A biological cell can function in a different
manner on a material substrate (underlying substance), when compared to that in a
culture medium (in isolation). Although an understanding of cell fate processes (cell
growth/proliferation, cell migration, etc.) from the biological science point of view
is necessary, this needs to be adopted considering that a cell has to interact with a
material substrate. Such interaction is mediated via adsorbed protein on the surface
of a material. Similarly, the growth kinetics of bacteria in culture (in isolation) can be
different as to how they multiply in a microenvironment around a biomaterial. This
also has significant implication towards biofilm formation, which leads to prosthetic
infection.
Another important idea from biological sciences is how to qualitatively and quan-
titatively analyse cell functionality modulation on a biomaterial. This aspect is often
supported by how specific genes are upregulated/downregulated, which requires the
quantification of expression of mRNA, which are extracted from cells grown on a
material. With the advancement of the field in terms of gene-level analysis, bioma-
terials science is getting more and more firmly integrated with the biological science
discipline. Once a biomaterial is screened to have acceptable or desired cytocom-
patibility, the next important step is to evaluate the tissue-level compatibility of a
biomaterial, implanted in an animal model.

It needs to be emphasised that the central concept of biomaterials science

intelligently uses necessary elements of the biological science discipline at an
interface with materials science.
1.2 The New Science 9

1.2.2 Defining Biocompatibility

One of the pre-requisites for a successful biomaterial is its acceptance by the host.
This interaction and coexistence of a biomaterial, be it synthetic or natural, with
the biological system is the fundamental meaning of biocompatibility (see Fig. 1.4).
While it is relatively common to describe a successful biomaterial as biocompatible,
the exact nature of biocompatibility is still uncertain. Along the lines of the first
principle of Hippocrates that a doctor should do “no harm”, the main requirement
for biocompatibility of a material, whatever its end application, is that it should do
“no harm”. Biomaterials are distinct from other classes of materials in the sense that
they have to be biocompatible with the biological system.
Phenomenologically, the biophysical events at the interface of a synthetic mate-
rial and the biological system have been described in Fig. 1.5. Proteins are adsorbed
within seconds of a material being placed in a biological system and their conforma-
tion changes can only be probed using molecular dynamics (MD) simulation or other
computational studies. If the adsorbed proteins express desired biological functions,
then they mediate the interactions with the biological cell. In an effort to establish
better interactions, a cell changes its morphology and can expand on a material
surface. Subsequently, cell–cell interactions and extracellular matrix formation take
over in the chronology of the biophysical events. At the tissue level, ECM deposition

L
E
N Tissue-material
G mm
interaction
T
H
Tissue response
S
C
A μm Cell-material
L interaction
E Cell fate changes

nm Molecular
interactions
Computational modelling

Fig. 1.5 Schematic of the interactions of an implantable biomaterial with the living system at
different length scales
10 1 Crossing the Boundaries

is followed by fibrous capsule formation in case of bioinert materials. In the case of

biodegradable materials, tissue formation synchronises with scaffold degradation.

The concept ‘biocompatibility’ is to be defined in the context of the targeted

clinical application.

It must be mentioned here that biocompatibility is application specific. This is

primarily because, different types of cells have different surface preference, and
accordingly, they adhere, proliferate, or differentiate. Such differences necessi-
tate that material surface properties be tailored for a specific biomedical appli-
cation. A multitude of issues—for instance, lack of desired physical properties
(elastic modulus/toughness), piezoelectric property (the ability of certain materials to
generate an electric charge in response to mechanical stress), and bactericidal prop-
erty (killing bacteria)—have triggered significant research activities on biomaterials
and implants.
Two key components need clarification. Biomaterials are directly linked to tissue
engineering applications for the regeneration of functional human tissues. Although
the body has its intrinsic self-healing properties, the need for healing and repair
arises due to injury or disease. Biomaterials are designed to provide an architectural
framework to encourage cell growth and tissue regeneration to enable biological
functions.

Scaffolds are physical structures of synthetic or biological material, or both;

that allow cells to attach, migrate, or modify their behaviour.

Biological cells are generally loaded (or ‘seeded’) into the scaffold to facili-
tate three-dimensional tissue formation, in vitro. The tissue repair process starts
in vitro by culturing cells on the scaffolds, which are subsequently implanted in
the host. Usually, this technique requires porous scaffolds to be biocompatible and
bioresorbable (naturally dissolving).
It is difficult to mark a line of distinction between tissue engineering and bioma-
terials science. Tissue engineering deals with porous scaffolds, which can be made
of ceramics, metals, and polymers as well as biological materials, like collagen or
other proteinaceous materials.

Nonporous biomaterials, which are used for load-bearing applications (e.g.

articulating joints) are commonly defined as implants.
1.2 The New Science 11

Common implant examples are ceramic femoral heads and stainless steel or
titanium-based stems in total hip joint replacement (THR) surgeries. The interac-
tions of scaffolds or implants with biological systems are fundamentally different,
and constitute the central theme of biomaterial science.

1.2.3 Structural Concepts

There are four kinds of biological macromolecules: carbohydrates, lipids, proteins,

and nucleic acids. Macromolecules such as polymers, are composed of many similar
smaller molecules linked together in a chain-like fashion. The smaller molecules
are called monomers. The most important macromolecule in a living system is the
protein and its monomer is the amino acid. An important example of a protein is
collagen, which is the most abundant protein in the human body. Proteins constitute
more than 50% of all major intracellular organic molecules and have a diverse range
of functions in a cell. Each cell in a living system may contain thousands of different
proteins.
In general, amino acids are structurally characterised by a carbon atom (the alpha
carbon) bonded to the four groups—a hydrogen atom (H), a carboxyl group (-COOH),
an amino group (-NH2 ) and a ‘variable’ group or ‘R’ group. The reaction of two amino
acids forms a peptide bond. The ‘R’ group varies among amino acids and determines
the differences among protein monomers. The structure of a protein is specified at
different levels, namely as primary, secondary, tertiary, and quaternary structure.
Secondary, tertiary, and quaternary structures of proteins can be differentiated from
one another on the basis of their degree of complexity.
The cells are the smallest structural and functional units of life that make up all
the plants, animals and single-celled self-sustaining organisms, such as bacteria and
yeast. In general, eukaryotic (‘truly’ nucleated) cells are enclosed by a lipid bilayer
and contain the necessary genetic material, needed to direct the continued propagation
of the cell. All the living cells, whether unicellular micro-organisms or just a tiny part
of a multi-cellular organism, look widely different, but share certain characteristics
in common. They are small ‘pockets’, composed mostly of cytoplasm (consisting
of cellular machinery and structural elements, such as free amino acids, proteins,
carbohydrates, fats, and numerous other molecules) enclosed within a phospholipid
bilayer membrane.
As far as different cell types are concerned, adipocytes help in storing/synthesising
fat compounds and constitute adipose tissues. While neurons are important cells
of central and peripheral nervous systems, astrocytes are a type of cell providing
structural support to neurons. In bone tissue, three types of cells are present. First,
osteoblasts, which are known as bone-forming cells, and second, the osteoclasts
which are bone-resorbing cells. Third, osteocytes are the matured osteoblasts. All
the three bone cell types are morphologically distinct. In skin tissue or endothelium,
the endothelial cells with close spacing are present and they protect the underlying
cellular structure.
12 1 Crossing the Boundaries

Tissues are at an intermediate level between cells and a complete organ in the
hierarchy. Four classes of tissues are connective, muscle, nervous, and epithelial
tissues. Connective tissues have fibrous morphology to provide structural support to
organs. Among different types of muscle tissues, smooth muscle is found in the inner
linings of organs, while skeletal muscle is attached to bone. Cardiac muscles enable
the heart to contract and pump blood throughout the organism. In the central nervous
system, neural tissue is contained in the brain and spinal cord, while in the peripheral
nervous system, the cranial and spinal nerves consist of neural tissue, which contains
neurons or nerve cells. Epithelial tissues contain closely placed epithelial cells, which
line organ surfaces.
Tissues can be classified into soft and hard tissues, primarily based on the elastic
stiffness or mechanical strength property. Hard tissues are mechanically superior to
soft tissues, and some of these tissues have desirable adaptability and multifunctional
properties. Mineralised tissues (bone, tendon, cartilage, tooth enamel and dentin) are
examples of hard tissues, which contain hard minerals and soft collagenous matrices.

Despite extensive research on synthetic biomaterials, often via biomim-

icking approaches, researchers are yet to develop a synthetic material with
matching mineralised tissue properties, and therefore, newer biomaterials
design approaches are under development.

1.3 Stem Cells and Regenerative Engineering

In view of its central importance in biomaterials science and biomedical engineering,

this section discusses stem cells and their importance in regenerative engineering.
Over the last one decade, stem cells and their promising applications in healing and
regenerative therapies have been the central foundation for a new scientific discipline,
regenerative engineering. Stem cells can differentiate into various cell types and are
fundamentally different from other cell types in terms of the following characteristics:
(a) Self-renewal: The ability to divide, usually after long periods of time, into more
stem cells while maintaining their undifferentiated state. (b) Potency: The ability to
differentiate into specialised cell types. It is known that stem cells are of five types;
these are (a) totipotent: can differentiate into any kind of cell of a total organism, (b)
pluripotent: can differentiate into all cell types, (c) multipotent: can differentiate into
a number of closely related cell types, (d) oligopotent: can differentiate into only two
cell types and (e) unipotent: can differentiate into a single or specific cell type; (e)
clonality, the ability to be derived along a specific lineage or from one source. In cell
biology, a clone represents a group of identical cells sharing a common ancestry.
1.3 Stem Cells and Regenerative Engineering 13

Stem cells can be derived from different sources, and accordingly, two major
classes of stem cells include, (a) embryonic stem cells (ESCs)—obtained from the
human embryo during the process of in vitro fertilisation. ESCs differentiate into all
the cell types and therefore are totipotent in nature. (b) Adult/somatic stem cells—
found in the differentiated tissues or organs, and these can renew themselves and
differentiate into major cell types (pluripotent in nature). They are mainly involved
in repair and maintenance of tissues or organs.
Further, stem cells can be classified into three types, (a) haematopoetic stem
cells, which can differentiate into blood cells, (b) mesenchymal stem cells, which
are derived from bone marrow and can differentiate into multiple cell types, and (c)
adipose stem cells, which are derived from fat cells. There are two other stem cell
types; (i) amniotic stem cells found in the amniotic fluid and (ii) induced pluripotent
stem cells (iPSCs), wherein the former type can be sourced from the amniotic fluid.
iPSCs are mature cells genetically reprogrammed by certain transcription factors that
have a pluripotent stem cell state.
The seminal work by Takahari and Yamanaka on the discovery of induced pluripo-
tency was awarded the 2012 Nobel Prize in Physiology and Medicine; jointly with
Sir John B. Gurdon.

In the field of medical science, significant clinical research is currently

underway to use stem cells (stem cell therapy) for the treatment of the
host of diseases, such as diabetes, rheumatoid arthritis, Parkinson’s disease,
Alzheimer’s disease, osteoarthritis, repairing hearing and vision loss, cardiac
infarction, Crohn’s disease and also for wound healing applications.

The impact of stem cells in tissue engineering can be substantiated with the help
of a few specific examples. Cartilage tissue contains the characteristic chondro-
cytes and the differentiation of hMScs to chondrocytes is known as chondrogenesis.
The myogenesis of hMScs leads to the formation of smooth muscle cells, which
are present in the musculoskeletal system and also in other parts, e.g. lining of
blood vessels or digestive tract. Similarly, cardiomyogenesis of hMScs results in the
cardiomyocytes, which form the cardiac tissue and this cell type is one of the known
cell types, which does not grow easily in culture. In patients suffering from blood
cancer, one of the clinical treatment options can be to transfuse haematopoietic cells.
Another important cell type is pancreatic islet cells, which has larger relevance in
controlling blood sugar level and is therefore relevant for the treatment of diabetes.
14 1 Crossing the Boundaries

1.4 Unmet Clinical Needs and Clinical Perspective

on Biomaterial Implants

In the last few decades, human healthcare needs have stimulated research activities
in the fields of biomaterials science and biomedical engineering. Studies indicating
significant evolution in materials science and engineering in terms of developing
potential biomaterials for healthcare have been widely published in the literature
during the last few decades. Commensurate with improvements in medical science,
considerable research has been pursued in the areas of biological, chemical, and phys-
ical sciences. In this perspective, researchers made considerable efforts to understand
the molecular biology aspects of some of the life-threatening diseases, and engineers
have attempted to develop various diagnostic tools, as well as synthetic implant
materials, to assess the disease state or to repair the damaged tissues. The quantifi-
cation aspect in the disease diagnosis has enabled better healthcare or more timely
treatment.

Among various diseases impacting human life, cardiac-related diseases, cancer

and neurodegenerative diseases are among the life-threatening diseases, while
a large number of patients also suffer from orthopaedic, i.e. bone/joint-
related diseases. The translational research on biomaterials should, in principle,
therefore be driven by the unmet clinical challenges in the global scenario.

In most cases, complicated revision surgery is needed after a few years of implan-
tation. The discovery and design of a material for hard tissue replacement with the
desired characteristics, namely long-term durability without significant degradation
in physical and mechanical properties, is a major area of research in orthopaedics. In
different anatomical parts of the human patient, metals, ceramics, polymers, and their
composites with acceptable biocompatibility are being used as artificial implants.
In vitro biocompatibility assessment requires expertise from molecular biology,
microbiology, and other branches of biological sciences. An in vivo biocompatibility
study requires the participation of a veterinary surgeon, to assist in experiments
with small, medium to large-sized animals. The safety evaluation of biomaterials
requires toxicity studies, both at cell and gene levels. This requires the involvement
of toxicologists.
A number of examples related to human diseases will be provided below to
substantiate the above discussion. For example, a femoral head in total hip joint
replacement (THR) needs to sustain complex biomechanical stresses, which are to
be evaluated using burst strength measurement and hip joint simulator experiments.
Similarly, the heart valve prototype has to sustain a large number of fatigue cycles.
Biomechanical considerations are equally important in dental restorative applica-
tions. The subsequent sections highlight key clinical needs in India, with reference
to some of the developed nations, however, this is not an exhaustive list.
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial Implants 15

1.4.1 Musculoskeletal Surgery and Orthopaedics

Annually, around 1,20,000 knee replacements are carried out and 75,000 hip replace-
ment are carried out in India. The American joint replacement registry (AJRR) has
reported an exponential growth in the number of total hip replacement (THR) proce-
dures in the USA during the last decade. In addition, the burden of revision surgery is
more than 10%. In an increasingly ageing—and obese—world, weight-bearing joints
of the hips, knees, and spine are under siege. Total hip or knee replacements are rising
exponentially. It is estimated that by 2030, the number of total knee replacements
performed in the USA will increase by more than 600% compared to that of 2005,
while total hip replacements are expected to increase by almost 200% over the same
time period. In India, knee arthritis is emerging as the fourth most common cause of
physical disability, while the joint replacement market is growing in double digits.
Among the musculoskeletal diseases, arthritis or other rheumatic diseases are
most prevalent in India.

Clinically, two variants of arthritis are osteoarthritis (OA) and rheumatoid

arthritis (RA). These diseases are associated with severe pain and in the most
critical conditions, can potentially render the joints dysfunctional.

Many orthopaedic surgeons regularly treat osteoarthritic patients, who visit the
clinics with the complaints of severe pain around all types of load-bearing joints like
hip, knee, and spine joints. X-ray radiography analysis mostly reveals the wear and
tear of joints as the primary cause of such problems, often affecting the cartilage
between two joints, or other problems, like bone overgrowth and joint damage.
Clinical investigations over last few decades reveal the concept of aseptic loos-
ening, initiated by the release of significant wear debris particles from the articulating
joint surface (see Fig. 1.6). These wear debris particles can cause downstream inflam-
matory reactions, leading to the activation of osteoclasts, leading to resorption of the
bone cells. RA normally is initiated at the linings of load-bearing joints and is the
manifestation of the attack by body’s own immune system. RA can be even more
painful as it may affect other joints and sometimes organs, like heart or lungs. Apart
from OA or RA, osteoporosis is another musculoskeletal disease, involving thinning
and weakening of bone.

Osteoporosis is commonly attributed to bone loss and deficiency of the bone

mineral content in elderly patients.

In the extreme case of severe functional loss of joints, surgical intervention by the
orthopaedic surgeons is the only treatment option. The natural joints in the muscu-
loskeletal system can be replaced by the synthetic implant system in orthopaedic
16 1 Crossing the Boundaries

Fig. 1.6 Clinical perspective of total hip joint replacement (THR): Femoral head (Co-Cr) and
Acetabular socket (UHMWPE) in THR surgery—such devices are reported to release wear debris
particles, causing inflammation (need for revision surgery)

surgeries to restore natural joint-like functionalities in the treated patients, and gener-
ically, this treatment option is known as total joint arthroplasty (TJA). These clinical
procedures are commonly named after the type of joint that is being replaced. For
example, the clinical terms, total hip joint arthroplasty (THA) refer to the replacement
of the hip joints; similarly, total knee arthroplasty (TKA) refers to knee replacement.
In the case of THR, commercially available femoral hip stems are an example of
an ongoing innovation (Fig. 1.6). The material for the femoral stem can be typically
stainless steel or Ti-alloys. The acetabular liner-femoral head combination can be
ceramic–polymer or metal–polymer or metal–metal. Among these options, ceramic–
polymer mating combinations are by far the most widely accepted clinically, because
of their better biocompatibility property. As far as THR assembly integration is
concerned, the press fit concept, as well as cementless or cemented hip systems, are
the two major options. While bone cement (e.g. PMMA) is used for the cemented
stem, this is not the case for the cementless stem, wherein bioactive HA is coated
onto the stem for better osseointegration.
For the problem of osteoarthritis, which is associated with chronic joint pain,
the potential solution is an implant with improved wear resistance and mechanical
strength. The development of a chondrogenic scaffold and injectable cartilage are
proposed as potential solutions to osteoarthritis. Osteomyelitis is associated with
infection at the fracture site of bone which might spread to the nearby tissue.

Biocomposite mixed with antibiotics (STIMULAN® ) is already in the Indian

market, but it is still not affordable for a large cross-section of society.
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial Implants 17

a b c

Fig. 1.7 (a) Clinical radiograph of osteoarthritic knee, (b) Total knee replacement implant, (c) Post-
operative radiography after knee surgery

In terms of patient specificity, different sizes of femoral head and respective liner
combinations are commercially available. In the case of knee replacement surgery,
the device components have different sizes and shapes than hip replacement. In
particular, the knee femoral component and tibial trays are the major components of
TKR (Fig. 1.7). In cases of accidents or trauma, the reunion at the site of bone frac-
ture and osseointegration (integration of non-biological origin implant to an osseous
system) are some of the clinical challenges. There have been recent advances in the
use of biodegradable polymers to address such challenges.

1.4.2 Dental Restoration

The poor state of the nation’s teeth is evident from reports that reveal that over half
of Indians have experienced tooth loss. Tooth decay has become an epidemic.

The level of complete edentulism (toothlessness) in the general population

varies from 14 to 16%.

Edentulism in the elderly, above age 65, is around 91.25% in both urban and rural
India. An initial cost estimate analysis indicates that indigenous dental implants are
twice as cheap when compared to the cost of imported implants in the market.
With respect to dental reconstruction, a few clinical cases highlighting the use of
implants in dental surgeries are shown in Fig. 1.8. Abfraction is a physico-mechanical
loss of tooth architecture, that is not caused by tooth decay and is located along the
gum line. This affects mostly the enamel and the dentin part of the crown. The
development of moderate and steady peptide-releasing biomaterials, which will be
able to regenerate or cure the area, as well as a temporary supporting material in the
affected region may be a probable solution. Another challenge is to address dental
caries, which can be described as cracks, channels, pits, grooves, and cavities in
18 1 Crossing the Boundaries

a b c

Fig. 1.8 Dental surgeries requiring implants (a) Ridge augmentation (b) Peridontal surgery with
grafts (c) Mandible surgery (d) Full mouth rehabilitation

tooth structure. This can originate in the back teeth, between teeth, around dental
filling or bridgework and/or near the gingival margin. The development of a suitable
biomaterial, which will be able to form a strong and long-term bond with dentin for
treatment of caries, can be a potential solution. Edentulism requires the use of dental
implants, which can be either metallic (e.g. Ti6Al4V) or ceramic (e.g. ZrO2 ). The
implant is placed into the jawbone of the patient, and on the top of an implant, the
dental crown is to be fitted to restore the mastication (i.e. chewing) function in a
patient.

The dental implants have specific geometric contour and designed thread
profiles for better post-operative stability and osseointegration.

1.4.3 Neurosurgical Treatment

In the context of neurosurgical applications, it is important to design biomate-

rials that improve interaction among neurons, bone, and meninges of the nervous
system. Also, prevention of scar tissue formation by astrocytes is extremely impor-
tant for neurological/cranial-based applications. Three major unexplored challenges
in the Indian context are childhood skull deformation, adult skull deformation, and
duraplasty. For the first two applications, the problems associated with titanium
implants need to be addressed. For duraplasty, the polypropylene and collagen-based
implants can provide potential biomaterials-based solutions.
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial Implants 19

Among various neurosurgical procedures, decompressive craniectomy (DC) is

one of the commonest treatment options in the management of traumatic brain
injury or stroke.

DC is a neurosurgical procedure performed in clinical cases of raised intracranial

pressure and impending herniation secondary to TBI or stroke. In such procedures, a
pre-defined part of the skull is removed. This first step allows the raised intracranial
pressure to return to the normal level and prevent any brainstem dysfunction. In order
to restore the desired functioning of the underlying brain cortex, the craniectomy
defect is to be closed with autologous bone or an implant (bone flap), in a follow-up
surgery known as cranioplasty. A large array of materials ranging from auto/allografts
and synthetic materials such as acrylic, ceramics, and polyether ether ketone (PEEK),
with or without osteo-inductive growth factors have been used by neurosurgeons to
repair cranial bone defects.
In cranioplasty surgery, titanium and stainless steel-based alloys have been estab-
lished as the most promising implant materials, but other materials such as PEEK or
PMMA are also clinically used with reasonable success in terms of desired functional
outcome (an example is shown in Fig. 1.9). Biodegradable polymers are most widely
used as screws and cranial plates; however, their fracture during implantation is a
disadvantage. All these clinical and associated issues require focused translational
research programmes in this direction.

3D CT Scan
Images showing
craniotomy defect

Front View Back View Lateral View Superior View

II Intraoperative Implant Fixation

a b c d

Fig. 1.9 A recent clinical study on cranioplasty surgery by neurosurgeons in collaboration with
the author’s group. I Conversion of CT Scan DICOM data to stl* file by 3D Slicer for modelling
of the craniotomy defect. II Intraoperative cranioplast implant fixation. (a) Depressed area with
incision: skin flap and pericranium are retracted exposing the dura (b) The dura is incised relieving
the subdural pressure (c) Polymethyl methacrylate (PMMA) custom bone flap is fixed with titanium
screws/plates (d) An epidural drain is placed and the skin is closed with staples
20 1 Crossing the Boundaries

In many neurosurgical treatments, the current clinical therapeutic methods for the
rescue and repair of damaged neural tissue are reported to be ineffective, as they do
not provide functional recovery of the nervous system.

Several research groups in India and abroad have worked towards the use
of functional biomaterials-based platforms, and further combining them with
stem cell-based therapies to mimic the natural microenvironment of the glial,
neuronal, and stromal cells of the nervous system.

The functionalities of biomaterial-based platforms provide 3D matrices with

desired pore sizes, porosities, elasticities, and wettability along with various chem-
ical, electrical, biological, and topographical cues that favor cellular attachment,
growth, proliferation, directed alignment, and differentiation as well as proper
nutrient flow for neural tissue regeneration.
Furthermore, considering the inherent presence of electrical fields and synapses
in the nervous system, the conductive biomaterials-based platforms, such as films,
hydrogels, fibers, composites, and flexible electronic interfaces, biophysical stimula-
tion have also been used through application of electrical stimuli to enhance the nerve
regeneration process. These platforms have been particularly used for controlling
neurite extension, directed migration of neuronal and glial cells, and differentiation
of stem cells.

The conductive polymer or carbon-based platforms hold significant potential

to manipulate cellular behavior and to promote neural regeneration.

However, the properties of these platforms, along with their precise control
on cellular mechanisms, should be further improved for clinical translation. The
microstructural and mechanical properties of these platforms, along with electrical
conductivity and biodegradability, require certain improvements to better mimic the
extracellular matrix (ECM) and to be applicable in clinic. There are still a number
of unknown aspects regarding the relationship between the electrical properties and
cellular functions, particularly from a mechanistic perspective.
Elucidating these relationships will pave the way for development of novel and
functional platforms not only for neural tissue engineering, but also for other tissue
engineering applications including skin, muscle, cardiac, and even brain–computer
interfaces. In addition, the use of biodegradable conductive platforms in tissue engi-
neering applications can potentially enable minimally invasive implantation and
manipulation of cells through remotely applied electrical stimuli. This can prevent
additional surgical interventions, therefore improving the experience of patients.
Cervical arthroplasty after anterior decompression with insertion of a prosthetic
disc has been suggested as an alternative to anterior cervical fusion. Cervical disc
replacement aims to maintain intervertebral movement. Currently, four prostheses
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial Implants 21

with varying design principles (materials, range of motion, insertion technique and
constraint) are available. Early studies show that in the short term, the complication
rate and efficacy are no worse than for fusion surgery. As spinal surgeons enter a new
era of the management of cervical spine disease, it is hoped that improvements in
these prostheses are made in terms of implantable biomaterials, design, and clinical
outcomes.

1.4.4 Cardiovascular Treatment

Cardiovascular diseases are considered as the primary causes responsible for increase
in mortality rate worldwide. It has been recognised that scarred cardiac muscle results
in heart failure for millions of heart attack survivors worldwide. When a blood vessel
is blocked, the myocytes die due to oxygen deprivation, resulting in scarred tissue
formation. The scarred cardiac muscle can potentially lead to heart failure due to
gradual ventricular remodeling, unless the damaged area can be restored or replaced
with new tissue or the blocked arteries can be decoagulated to remove the plaques
using a stent.
Despite significant progress in the field of medical sciences, heart attack (myocar-
dial infarction) is still regarded as a major killer even today. This is primarily because
of the fact that it is difficult to regenerate the diseased cardiac tissues. In the case of
myocardial infarction, i.e. ‘heart attack’, cardiac tissues are largely damaged.

In the heart, the functionality of cardiomyocytes (a contractile muscle cell

that generates part of the myocardium tissue of the heart) and neurons (an
electrically excitable cell that processes and transmits information by electrical
and chemical signaling) depends on the continuous conductivity property.

However, such conductivity may break down during heart disease or malfunction.
A myocardial infarction can occur when a major blood vessel supplying the heart’s
left ventricle is suddenly blocked by an obstruction, mainly because of a blood clot
(Fig. 1.10). This destroys the cardiomyocytes and neurons, leading to the formation
of dead tissue, which ultimately results in myocardium denervation. Nerve damage
to cardiac tissue can result in nerve growth in the left ventricle and development of
arrhythmias.
The existing clinical treatment options include coronary artery bypass surgery,
angioplasty, tissue-engineered cardiac patch, and heart transplant. In the case of
angioplasty, coronary stents are used, and those expand when inserted into the
damaged artery to clean up the undesired plaques. This results in better blood circu-
lation in cardiovascular system. In case of the cardiac patch, the tissue-engineered
scaffolds should have cardiac tissue-like conductivity property and the ability to
22 1 Crossing the Boundaries

Fig. 1.10 Biomaterials based approaches for cardiovascular treatment. (a) Cross section of a middle
sized artery. Adaptation of image by Bernhard B. Singer, Stem Cell Reviews (2008), 4 (3):169–
77. (b) Cross section of an artery subjected to atherosclerosis. Adapted from an image by Carla
Masia et al. Universita Degli Studi Di Pavia Thesis, “Constitutive modelling of a biodegradable
polymer” (2007–2008). (c) Myocardial infraction and representative illustration of biomaterials
based interventions. Angioplasty image source: www.medgadget.com

support the proliferation of the beating cardiomyocytes. Apart from the biocompati-
bility properties, it is important that that an ideal cardiac patch should have sufficient
electrical and micro-mechanical properties to ensure the natural contractile nature
of myocardium. The heart transplant is the chosen clinical treatment option, only in
the event of total heart failure and the lack of the feasibility of the above-mentioned
clinical treatment options. Among all these treatment options, the bypass surgery and
heart transplant are very invasive in nature, while the cardiac patch-based treatment
is minimally invasive in nature, with the possibility of fixing the dead cardiac tissue.
After implantation, a medical device or prosthesis undergoes a lot of modification
at its surface due to various immune cellular complement activation, resulting from
local tissue injury.
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial Implants 23

In cardiovascular physiology, a healthy endothelium not only plays an impor-

tant role in controlling blood fluidity, but also inhibits the adherence and
aggregation of macrophages and platelets.

Further, healthy endothelial cells (inner lining of blood/lymphatic vessels as well

as inner lumen of heart) suppress the proliferation of smooth muscle cells (SMC)
and regulate various inflammation processes. Therefore, the compatibility of blood
contacting devices with endothelial cells and SMCs is important.
Five approaches are investigated in the bioengineering community for developing
or improving the treatment options for cardiovascular diseases. One of the approaches
is to deliver the stem cells to the infarct or direct injection; while in another approach,
the cardiomyocytes from the patient’s own pericardium are grown or printed by 3D
bioprinting in a thin-layered form on a patterned hydrogel, followed by surgical
implantation. Another tissue engineering-based approach is to deliver polymeric
scaffolds with cell suspensions via injection or catheter. Alternatively, cells-seeded
biological/synthesis 3D scaffolds are cultured in a 3D bioreactor and subsequently
implanted into the infarct. The use of blood-compatible coatings on coronary stents
is also investigated in an effort to develop better haemocompatible devices as well
as to assess the ability to release blood-thinning drugs, when implanted into the
diseased aorta. Another approach is the use of biophysical stimulation to regenerate
the matured cardiomyocytes, often using a tissue-engineered scaffold or implantable
biomaterials, as discussed in Chapter 3. Many of these promising approaches are still
in pre-clinical validation or in clinical trial stage.
In the context of the bioceramic coated implants for cardiovascular treatment, it
is noteworthy to mention that while Ti-based or NiTi-based shape memory alloys are
clinically used as coronary stents, many of these materials do not have the greatest
combination of blood compatibility and cytocompatibility. The use of bioceramic
coatings, like TiN/TiAlN on Ti6Al4V, has been investigated and their blood compat-
ibility has been established in various research groups. Apart from antibacterial prop-
erties and cytocompatibility with endothelial cells, the blood-contacting devices, like
coronary stents, should have lower haemolysis, less platelet adhesion and aggrega-
tion, without causing any morphological deformation to red blood cells and extended
blood coagulation time. In a recent research work from the author’s group, a new
generation of SiCx Ny Oz coatings on Ti substrate was developed for the cardiovascular
application. These coatings demonstrated clinically acceptable haemocompatibility
parameters and much better biocompatibility than uncoated Ti. These coatings have
been further taken for pre-clinical validation.
Considering another treatment approach of electrical stimulation, it is important to
recognise that the cardiac muscle tissue in the native heart has specialised electrical
signal conduction and propagation pathways, such as electromechanical coupling
via gap junction channels, and this coordinated electrical signaling mechanism is
involved in heart contraction.
24 1 Crossing the Boundaries

Cardiac pacing and defibrillation are among the most important heart disease
treatment functions of electrical stimulation.

Cardiac arrhythmias or irregular heartbeat, leading to speeding up or slowing

down of the heart rate, are treated by surgical implantation of a cardiac pacemaker
in the chest close to the heart. An increasing number of publications showed the
association of exogenous EF in inducing cardiogenesis in embryoid bodies (EBs)
derived from hESCs. One of the greater challenges is to produce functionally mature
cardiomyocytes with natural heart-muscle-like beating behavior.

1.4.5 Urological Treatment

In the field of urological treatment, clinicians need to treat patients with persistent
medical conditions, that generally compromise the natural functioning of the urinary
bladder to store and evacuate (void) urine (see Fig. 1.11). A large number of patients
worldwide, estimated to be more than 400 million, are reported to suffer from urinary
bladder-associated physiological disorders, with bladder carcinoma (BC) being the
most common cause of morbidity. In fact, BC is considered to rank ninth globally,

Bladder augmentaƟon
Bladder graŌ to improve
capacity and compliance
Neo-bladder
ReconstrucƟon of
SyntheƟc bladder

Mucosa
ConnecƟve Tissue
Muscularis Propis
Perivesical Fat

Ureteral stent
Indwelling stent allowing
urine to bypass a stone

Urethral conduit
Tubular graŌ to facilitate
natural voiding

Fig. 1.11 Urinary bladder-associated pathologies and potential clinical applications of biomaterials
in urological reconstructive surgery
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial Implants 25

with respect to other malignant diseases and is also the thirteenth commonest cause
of cancer related deaths.

In India, three men and one woman, among every 1,00,000 citizens, develop
bladder carcinoma every year.

To address these urological problems, one of the clinical treatment approaches is

to design and implant a functional equivalent of natural counterpart, based upon the
concept of tissue engineering and regenerative medicine. Another treatment approach
is based on an alloplastic prosthetic bladder with a passive reservoir, which facil-
itates low pressure urine storage as well as subsequent volitional voiding. For the
former approach, biodegradable polymers are to be used, and for the latter, the use
of biostable/bioinert implants is preferred.
There is a current need for a new material for replacing the bladder in bladder
transplantation. The neo-bladder should have desired properties and most importantly
should be resistant to encrustation. Thus far, a pouch derived from the intestine has
been used for bladder replacement. For surgery related to the urethra, urologists
require a biodegradable material for stents and new biomaterials to replace the urethra
and ureter, which do not get encrusted.
Concerning biomaterials in reconstructive urology, polyesters of alpha-hydroxy
acids, such as polylactic acid (PLA), polyglycolic acid (PGA) and their copolymer,
polylactic-co-glycolic acid (PLGA) are the key examples of synthetic biodegradable
polymers to be developed into an implantable neo-bladder prototype and clinically
tested in human patients. In recent times, a new approach of using hybrid scaffolds
with the binary combination of a natural biopolymer and a synthetic biomaterial
has been conceived in laboratory-scale research. In such an approach, the natural
biopolymer provides the molecular signals to direct cell fate and cellular function-
ality, while the synthetic counterpart contributes towards structural reliability and
tunable degradation.

The most successful clinical trials in bladder tissue engineering used the cell
seeded hybrid scaffold of collagen and PGA, and this was conducted by Atala’s
group at Wake Forest Institute of Regenerative Medicine, USA.

Although scaffolds based on combinations of collagen with PCL or PLGA have

been also investigated for potential urological applications, those have not yet been
translated to human clinical studies.
26 1 Crossing the Boundaries

1.4.6 ENT Surgery

The National Sample Survey Organization (NSSO), India, reported hearing loss as a
major cause of speech disability in about 3 per 1000 persons with speech disability.
Various reports from around the world have suggested that at least one child per 1000
is born with bilateral sensorineural hearing loss (SNHL) of at least 40 dB and four
in 10,000 have profound SNHL.

As per World Health Organization (WHO) estimates, 5% of world population

or 360 million persons have hearing loss, out of which, 28 million are children.

As per census bureau reports in 2010, 56.7 million out of 308.7 million people
in USA have been living with some form of disability, corresponding to 19% of the
total population, and among them, 10.8% of those with disability were noted to be
below the poverty line. Over 7.6 million people experienced difficulty in hearing,
including 1.1 million whose difficulty was severe. About 5.6 million people used a
hearing aid.
Nearly, 27 million people are suffering from hearing disability in India. Among
them, 5 million people have hearing disability amounting to 19% of total disability.
The number of persons with hearing disability stands at 18.9% of 2.21% of total
disabled population. Hearing disability is more among females compared to males
and more in urban areas compared to rural areas. Among the total disability, the
number of people having hearing disability increases with age and has been seen to
reach its maximum level at 90 years of age. It has been reported that children account
for 8% of the hearing disabled, adding up to 28 million among 5% of world population
with hearing disability, although 7% of the hearing disabled people have congenital
defects. During the rehabilitation process of hearing disability, it is required to retain
the residual hearing of the patient.
The sensorineural-type deafness may require complicated surgical procedures
including cochlear implant (CI) fixation. In India, all high-quality CI are imported,
attributing to higher costs. The known clinical complications of cochlear implants
generally include those related to surgical technique, post-operative care and device
malfunction. Lesser known complications include facial nerve stimulation and non-
responsive auditory nerve, which can be avoided. Though the success of CI is well
documented and patient compliance is very high, CI can induce severe inflammatory
reactions in many patients, which can cause damage to left over undamaged hair
cells which will result in loss of residual low frequency hearing.
One of the major challenges in cochlear implant surgery is to preserve functional
hair cells. Initial attempts are focused on a more refined surgical technique, though
electrode modification is another option. The most important pathological pathway
responsible for apoptosis of hair cells is excessive reactive oxygen species (ROS)
production after CI fixation.
1.4 Unmet Clinical Needs and Clinical Perspective on Biomaterial Implants 27

The electrode surface modification in cochlear implants to reduce ROS produc-

tion in the auditory system represents one of the unmet clinical needs in the
field of ENT surgery.

In this direction, a research programme in India is being taken up to find a solution

to retain the residual hearing of hearing disabled patients, which is discussed in
Chapter 3.
Limited resources, expensive devices, and the problems related to surgical tech-
niques are major concerns for the success of the biomedical devices used to overcome
hearing disability. As the biomaterial is an outcome of interdisciplinary effort from
engineer, physician and biologist, a joint effort by all of them is expected to make
successful devices and find suitable solutions for the existing problems of different
biomedical devices.

1.5 The Tailpiece

Last but not least come all the concepts and elements that prop up biomaterials
science. It is expected that all the concepts and unmet clinical needs, discussed in this
chapter, should be used as guidelines to design biomaterials. The field is now, more
than ever, a coming together of various science and engineering disciplines. It has
seen the emergence of novel materials that have found critical medical applications:
from bone replacement/healing to neurosurgical and urological applications. And at
its heart lies the science, where biomaterials interact with living cells and tissues.
However, the biomaterials of the future are expected to go far beyond that, where
cutting-edge designs, biocompatibility, and computational insights are expected to
provide better clinical solutions.
Chapter 2
Economic Impact, Healthcare Initiatives,
and Research Funding

Abstract The potential economic and societal impact have driven significant
research programmes on biomaterials and implants over the last few decades glob-
ally. However, the outcome has not yet been too significant in India, as more than 80%
of the implants used in Indian hospitals are still imported! It is therefore important
to consider the market value of implants and the quantum of business related to the
field of biomaterials. In this context, this chapter introduces the potential economic
impact of the indigenous development of high-quality biomedical implants, which
also drives many national policies to facilitate translational research. Against this
backdrop, governmental funding agencies have started several new initiatives. This
chapter discusses the above aspects and briefly mentions the international status also.
In addition, the present status of medical and bioengineering education is briefly
mentioned.

© Springer Nature Singapore Pte Ltd. 2020 29

B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0_2
30 2 Economic Impact, Healthcare Initiatives …

2.1 Potential Economic Impact of Innovation

In the preceding chapter, the field of biomaterials science is introduced. Many key
examples are provided to demonstrate the critical use of implants in various disease
treatments. For example, geriatric care is of major concern in India. The World Health
Organization (WHO) estimated that 130 million people will suffer from osteoarthritis
and 40 million people will be severely disabled by osteoarthritis by 2050. In India,
20% of the disabled population has a movement-related disability, accounting for
about 53 lakhs, and this figure is increasing annually since 2011.
Currently, there are more than 300,000 cases every year of total knee replacements
(TKR) and more than 100,000 cases every year of total hip arthroplasty (THA) proce-
dures in India. The available articulating joint implants generally offer a trouble-free
life for about 10–15 years, which is inadequate, considering the increased lifespan for
humans in many developing nations. Therefore, a search for ideal prosthetic mate-
rials together with treatment methods, reconstructive solutions, and surface designs
is currently being pursued in the field of orthopaedic biomaterials.
The increase in the number of revision surgeries is commensurate with the rate
of increase in primary surgeries, and the majority of revisions are due to prosthesis
failures—hence, the increasing demand for improving implants and thorough char-
acterisation, globally. Trauma injuries due to accidents are another cause of mortality
and disability. Although timely treatment is essential, the cost of surgery for cases
of major trauma injuries or disabilities remains unaffordable to the majority of the
population in many developing nations, due to unavailability of affordable implants,
such as hip and knee implants, among other causes.

Significant socio-economic impact can be realised if we improve and develop

the translational ecosystem that is the key to affordable healthcare in India.

2.1.1 International Market

According to industry estimates, the global biomedical devices market in 2020 is

valued at around 470 billion USD, equivalent to 47,000 crores INR. The market is
expected to grow at a CAGR of 7.5% over the next 5 years, as shown in Fig. 2.1.
Globally, the principal markets are North America (50%), Europe (12%), Japan
(10%), Germany (6%), and rest of the world (22%).

North America is the largest market for implants, and Asia–Pacific is the fastest
growing market with India being a key player in the Asian market.
2.1 Potential Economic Impact of Innovation 31

Indian market (billion USD)

Global market (billion USD)

Fig. 2.1 Global medical devices market versus Indian medical devices market demand and forecast,
2016–2024 (Source Market Study of Advanced Ceramics and Composites in the Healthcare Space,
Frost and Sullivan, 2020)

Out of the total healthcare expenditure in Europe, around 7.2% is attributed to

medical technologies. In 2017, more than 13,000 patent applications were filed with
the European Patent Office, in the field of medical technology. The European medical
technology industry employs directly more than 675,000 people. There are almost
27,000 medical technology companies in Europe. Europe’s top export locations for
medical devices were USA (40.7%), China (9.6%), and Japan (6.6%).
The general trend of the bone implants market is shifting from autograft (autolo-
gous bone) to allograft (synthetic bone). In the case of the autograft, the acceptance
by the body is very rapid, but the time involved and pain created is much greater
than when compared to that of the allograft. Inferences on the implant market for
treatment of specific human diseases can be realised only when one compares the
market growth in that specific implant domain. The global orthopaedic market is
approximately 30% of the total implants market and the market shares of segments
in 2020, and as expected in 2023, are shown in Fig. 2.2. It is evident that relative
changes in the segment shares for orthopaedic large joint implants, spinal implants,
and orthopaedic trauma in 2023 are predicted to be marginal with respect to the
present market status in 2020. A similar scenario is also expected for orthopaedic
small bones and joints, orthopaedic biomaterials, and orthopaedic soft tissue regen-
eration. The overall trend therefore shows a steady, yet slow expected market growth
in the THR application domain. The THR market is further subdivided into three
sectors: total hip replacement, partial hip replacement, and revision and hip resur-
facing. Overall, the total market segment share for orthopaedics is expected to remain
around 70% and that for spinal, around 30% (see Fig. 2.2).
Top international manufacturers in the orthopaedic domain include Baxter, Becton
Dickinson, Stryker, Cardinal Health, Abbot Lab, Siemens Healthineers, Royal
32 2 Economic Impact, Healthcare Initiatives …

Fig. 2.2 Global orthopaedic market segment shares in 2020, and as predicted in 2023 (Source State
of the Global Orthopedics Market 2019/20, iData Research)

Phillips, GE Healthcare, Johnson and Johnson, and Medtronics. As far as the manu-
facturing sector is concerned, the medical 3D printing global market is estimated to
reach $1.2 billion by 2020 at a high compound annual growth rate (CAGR) of 29%.
Medical applications for 3D printing include surgical models, bioprinted tissues,
and medical implants, which account for 65% by value. Polymers are the preferred
materials for 3D printing, and they account for about half of the market revenue in
the materials market.
The Indian spine market does not have many domestic players. Fusion devices
currently make up the largest market share for spinal devices, and the non-fusion
device market share is expected to grow through 2019. Medtronic, Zimmer Biomet,
and DePuy Synthes are dominating the market, while other players are Matrix
Meditec, Inor Orthopaedics, SH Pitkar, and Biorad Medisys. Globally, the market
for spinal implants is expected to grow at a CAGR of approximately 5.5% during
2017–2023, reaching more than $12 million USD during 2018–2024. The number
of spinal procedures performed each year in the USA is over 1.4 million, with the
greatest number being cervical fixation procedures (over 350,000 procedures yearly).
Interbody fusion procedures and thoracolumbar fixation procedures are the second
and third most common in the musculoskeletal implant sector. The European spinal
market size is approximately half that of the USA. Europe’s fastest growing segment
is the vertebral compression fracture market.

The gradual rise in spinal disorders, including lumbar spine stenosis, degen-
erative discs, disc herniation, and spinal stenosis among others, is one of the
major contributing factors for the growth of the spinal implant market.

The global spinal market, segmented by products, comprises spinal fusion

implants, spine biologics, VCF treatment devices, spinal non-fusion implants, and
spine bone growth electrical stimulation devices. The key players in the spine
2.1 Potential Economic Impact of Innovation 33

market are Medtronic, Johnson and Johnson, Stryker, NuVasive, Globus Medical,
and Zimmer Biomet.
Dental implants are made up of the implant, the abutment, and the crown and can
be used to replace single teeth or a set of teeth. They greatly improve the quality of
life from the point of view of oral health. Available in different sizes and shapes,
dental implants are employed according to the needs of the patient. The American
Association of Oral and Maxillofacial surgeons has indicated that 69% of adults, aged
between 35 and 44, could have lost at least one permanent tooth due to an accident,
gum disease, failed root canal, or tooth decay. By age 74, 26% of adults have lost all
of their permanent teeth. According to the market projections by GlobalData Medical
Intelligence Centre, the market value for dental implants is expected to increase from
$4 billion USD in 2020 to around $6 billion USD in 2028 (see Fig. 2.3). An important
observation is that the market is growing steadily and the projection indicates the
doubling of the market demand during 2018–2028 in the dental implant sector.
Looking at the larger global dental implants and prostheses market, it generated
$7.2 billion USD revenue in 2017 and was predicted to increase at a CAGR of 6.1%
during 2018–2024, reaching a value of about $12 billion USD in 2025 (Fig. 2.4). This,
along with the rising geriatric population, provides an opportunity for key players to
cater to the enormous untargeted population suffering from edentulism.
In the more advanced markets, computer-aided design/computer-aided milling
(CAD/CAM) has revolutionised dental care and the patient experience. It allows the
manufacture of crowns immediately within the clinic or hospital. Dental tourism is
evolving in emerging economies, such as India. Increasing economic stability and
dispensing power are further expected to accelerate growth of the market.
Market Value (billion USD)

Fig. 2.3 Global market prediction: dental implants market (Source GlobalData Medical Intelligence
Centre)
34 2 Economic Impact, Healthcare Initiatives …

Dental Implants and prostheses Craniomaxillofacial devices

and implants
Global Market Size
$7.2 billion USD $1.4 billion USD
(2017):

Expected Growth CAGR of 6.1% to reach a value of CAGR of 8.6% to reach a value of
During 2018 – 2024: around $12 billion USD by 2025 around $3 billion USD by 2025

CAGR: Compound Annual Growth Rate

Fig. 2.4 Market size for dental and craniomaxillofacial implants (Source GlobalData Medical
Intelligence Centre)

With respect to end-users, the customer base is made up of dental clinics and
hospitals, dental laboratories, dental colleges, and research establishments.

On the basis of dental implant type, the market is divided into tapered and
parallel-walled dental implants, which are manufactured from titanium and
lately, zirconia blanks.

The tapered implants sector share is 77.7%, and that of the parallel-walled implants
is 4.6%. The zirconia implant segment is forecasted to show significant growth, which
is expected due to the growing adoption of these implants (see Fig. 2.5). Major players
in the dental market are Straumann AG, Dentsply Sirona, Zimmer Biomet, Henry
Schein, and the Danaher Corporation.
The craniomaxillofacial (CMF) device product segment encompasses temporo-
mandibular joint (TMJ) replacement, CMF distraction, cranial flap fixation, CMF
plate and screw fixation, bone graft substitutes, and thoracic fixation. The global
CMF devices and implants market size was valued at $1.4 billion in 2017 and is
expected to grow at a CAGR of 8.6% over the period 2018–2024, reaching $3 billion
in 2025.

2.1.2 National Market

In India, 30% of the total healthcare expenditure is public spending, compared to

48.3% for the USA. Just 1.4% of the GDP is spent on public healthcare in India,
compared to 8.3% for the USA. India needs to increase its public healthcare expen-
diture. Considering that public healthcare is often the only recourse for the rural and
poor population, the public healthcare expenditure is expected to reach ~3% of GDP
by 2025.
2.1 Potential Economic Impact of Innovation 35

(a) Zirconia
implants

Titanium
implants

(b)

Fig. 2.5 Dental implants market sectors, revenue share (%) by type of implants (a) and growth rate
at different geographical regions in the world (b) (Source Dental Implants Market—Growth Trends
and Forecasts (2020–2025), Mordor Intelligence)

The business opportunity of medical devices in India is attracting not only multi-
national companies established in the area, but also corporate houses with presence in
related areas, such as pharmaceuticals, industrial ceramics, and precision machining.
The new entrants are exploring domestic acquisitions to gain a foothold in the market
and also international acquisitions to gain product and technology advantage.

In India, the industrial sector needs to improve its R&D capabilities in order
to collaborate effectively with academic institutions and national labs.

As in 2019, the medical device market in India was valued at around 15 billion
USD (see Fig. 2.1). The evolving market structure calls for companies to adapt their
strategies to participate in the growth opportunities, as the Indian market emerges as
a 20 billion USD business in 2024 (see Fig. 2.6). India is one of the fastest growing
medical devices markets globally—it has threefold higher CAGR compared to global
growth (Figs. 2.1 and 2.6). The Indian market is the fourth largest market in Asia.
36 2 Economic Impact, Healthcare Initiatives …

Fig. 2.6 Indian medical CAGR:23.2%

devices market demand and
forecast—by segments,
2016–2024 (Source Market
Study of Advanced Ceramics
and Composites in the
Healthcare Space, Frost and
Sullivan, 2020) CAGR:14.6%

The delivery of healthcare in India has significantly improved in the last decade.
Several large multi-speciality hospital chains, offering world-class treatment options
and facilities were established. Single speciality chains have also been established
more recently. These have contributed to the growth of medical tourism in India,
which is positioned to further grow, given the quality and cost-effective care in world-
class accredited hospitals, such as Narayana, Hinduja, Fortis, and Apollo Groups.
Imports are growing rapidly as world-class hospital groups build high-end infras-
tructure and open India to medical tourism, a growth which now adds 2 billion USD
to the Indian healthcare market. The National Medical and Wellness Tourism Board
has been recently constituted by the Ministry of Tourism in India, for promotion of
medical tourism and for support of the medical/wellness segment.
Many international patients travel to India every year for complex surgeries,
such as cancer treatments, while others travel for affordable procedures, such as
plastic surgery that may not be covered under patients’ insurance. India’s affordable
medical treatments, high-quality healthcare services, skilled medical staff, tradi-
tional medicine, wellness centres, and sightseeing attractions have made the country
a preferred destination for medical tourism.
The global medical tourism industry was valued at $76 billion USD in 2018 and
is expected to grow further at an average growth rate of 20%. Currently, India holds
approximately 18% of the global medical tourism market (approximately $14 billion
USD). Major medical tourism destinations are Thailand, Malaysia, Singapore, India,
South Korea, Brazil, Costa Rica, Mexico, Taiwan, and Turkey. Medical tourists travel
to these countries to avail of affordable and high-quality medical treatments. The
percentage of cost savings by country with respect to similar treatment in the USA
is shown in Fig. 2.7. Also, India is perceived as a preferred destination for joint and
cardiac surgeries by several neighbouring Asian countries and many African nations.
2.1 Potential Economic Impact of Innovation 37

Fig. 2.7 Indian medical tourism market: percentage of cost savings from medical treatments by
region compared to the USA, 2018 (Sources Ministry of Tourism India; Patients Beyond Borders;
India Brand Equity Foundation; Market Study of Advanced Ceramics and Composites in the
Healthcare Space, Frost and Sullivan 2020)

The medical tourists generally save around 77.5% of treatment costs in India,
compared to what they incur if they undergo similar medical treatment in the
USA.

Significant growth of the market (118%) is expected between 2020 and 2024.
Approximately 214 million patients are suffering from orthopaedic and dental-related
diseases. With respect to the need for dental treatment, 11–37% of edentulism occurs
in the age group of 65–75 in India. Dental caries is occurring at a rate of 70–80% in
the adult population.
The orthopaedic market is split evenly between the joints and trauma–spine
segments. The joints market in India has a predominance of foreign MNCs, whereas
the trauma–spine market is highly fragmented with a number of Indian companies
occupying the majority of the market share (revenues greater than $8 million USD).
Indian companies need CE marking and US FDA approvals to penetrate into global
markets. There has been a recent trend with multinational companies bringing in
Chinese products to compete with Indian players on price. Over 25,000 total joint
replacement procedures were registered in 2016 at over 740 hospitals in 200 cities
across India. The orthopaedic joints market is composed predominantly of hip and
knee segments.
The knee sector is predominantly dominated by multinational players, such as
Zimmer Biomet, DePuy Synthes, Stryker, and Smith and Nephew. Currently, their
products are better suited for western populations.

In view of different patient anatomy in Asian populations, effective customi-

sation of biomaterial implants is needed to meet the local requirements.
38 2 Economic Impact, Healthcare Initiatives …

Domestic players include Meril Healthcare, Inor Orthopaedics, Biorad Medisys,

TTK, and Sharma Orthopaedics. For example, Biorad Medisys manufactures Indus
Knee, India’s first totally indigenous posterior stabilised knee prosthesis. The
company has also launched India’s first registry initiative to map the clinical
performance of medical devices used in arthroplasty.
The hip sector has major multinational companies, such as Zimmer Biomet,
DePuy Synthes, and Stryker. Domestic players are Inor Orthopaedics, Sharma
Orthopaedics, Meril Healthcare, and SH Pitkar. However, they often lack total hip
solutions. In this market, approximately 200 companies generate revenues worth
$3 million to $5 million USD. Notable companies in this sector include Sharma
Orthopaedics, Matrix Meditec, and Inor Orthopaedics.
In the past decade, a few companies have set up innovation centres in India and
manufacturing units for medical devices. US-based Orchid Orthopedics has opened
a new manufacturing site in Pune and plans to serve the Asian and global markets by
providing additional manufacturing options. Stryker is interested in developing the
emerging markets of India and China and has set up an R&D centre in Gurugram
to develop products more suitable for Asian markets. According to the company,
emerging markets can contribute to as much as 12–14% of its global sales over the
period of 2016–2021. Zimmer Biomet and Indo-UK Institutes of Health (IUIH) are
planning to build the Biomet Institute of India, which will train more than 1000
orthopaedic surgeons a year on new procedures. DePuy Synthes established the
DePuy Institute for Advanced Education and Research in Chennai, which is expected
to train several hundreds of surgeons a year on the latest technologies.
In the national market, almost 80–85% of demand is met through imports. Imports
are highest in patient aids, implants, and instruments and appliances, while it is
lowest in consumables. Consumables and Diagnostic Imaging sectors dominate the
device market, occupying more than 50% of the market. There are around 750–
800 device medical device manufacturers, with around 65% of them operating in
the consumables segment. The Indian orthopaedic and prosthetic device market is
valued at $660 million USD and the dental product market at $290 million USD in
2020 (see Fig. 2.8). The overall projection is that the combined market will grow to
2.84 billion USD in 2024, as shown in Fig. 2.8.
In the coming phase of the Indian medical device industry, the products of domestic
companies are expected to be on par with imported products, to gain market share
despite the presence of foreign multinational companies, and also to emerge as strong
contenders in the rest of world export market. For example, domestic players with
products competing for key segments are Biorad Medisys’ knee/hip replacement
systems and Maxx Medical’s Freedom Knee Replacement Systems.
2.2 India’s Healthcare Initiatives and Translational Research Facilitation 39

Fig. 2.8 Indian orthopaedics

and prosthetics and dental 2.84
products demand and
forecast, 2016–2024 (Source
Market Study of Advanced
Ceramics and Composites in
the Healthcare Space, Frost
and Sullivan 2020)

0.95
0.80

0.46

2.2 India’s Healthcare Initiatives and Translational

Research Facilitation

Not only are the innovations important, but also, the initiatives which improve
access to healthcare are vital. The Ayushman Bharat Scheme is a national health
coverage plan for 500 million underprivileged citizens—through the scheme, the
Indian government has delivered INR 79.01 billion worth of free secondary and
tertiary treatment to beneficiaries across 224 hospitals at the national level (coverage
up to 5 lakhs per family). Under this scheme, population coverage may increase
from the current, approximately 40% of the nation, to as high as 75% in the next few
years. The Union Ministry of Health and Family Welfare plans to launch ‘My Health
Record’, a mobile app, which will support digital health and telehealth in India.
In 2015, the Government of India launched the initiative, Startup India. Subse-
quently, more than 3000 start-ups have been supported by seed funding from state
governments, via grants to incubators, loan interest subsidy, interest free loan, reim-
bursement of subsidy on lease rental and funds as monthly sustenance allowance,
product development assistance, and marketing assistance.

The Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB-PMJAY) Start-
Up Grand Challenge is a national initiative, that intends to stimulate the Indian
start-up community to generate solutions for empowering people to gain access
to affordable healthcare.

Launched by the National Health Authority in partnership with BIRAC and

Startup India, start-ups engaged in areas such as medical devices, digital health,
40 2 Economic Impact, Healthcare Initiatives …

health communications, hospital services and hospital management, and medical

workforce training are invited to innovate solutions in the healthcare sector.
Like other developing nations, India is facing several market-related challenges.
The market limiters in India are lack of industrial initiatives, such as stakeholder
network, regulatory initiatives, price control policies, lack of appropriate business
models, low public healthcare funding, and the presence of competitive global players
in biomedical devices.

The implants, that are highly expensive, run the risk of poor market acceptance.

The government is considering price control policies as an option to bring down

costs for patients. In order to have control on the price structure of imported implants,
recently, the Government of India has implemented a rise in import duty from 5 to
7.5% on several medical devices. Basic customs duty was lowered to 2.5% and
there has been an exemption from special additional duty (SAD) on raw materials,
parts, and accessories for the manufacture of medical devices. However, there are
mixed opinions as to whether this will help patients in the long term as this might
disincentivise both domestic and multinational companies from pursuing innovation.
A challenge for smaller players is not being able to build an influential network among
physicians and the advantage is for larger players, who are leveraging their network
with the medical fraternity and academia.
In Europe, medical devices are classified into three major classes (based on risk
and fault in functioning), with Class I being the lowest risk and Class III being the
highest risk. The Indian regulatory system should take safety as a major priority and
work towards such a classification, so that appropriate measures should be taken
as per the risk level. Also, health technology assessment (HTA) by the responsible
agency of each country is playing an important role in determining the appropriate
usage, coverage, or reimbursement for medical technologies at both national and
regional levels in Europe.

2.2.1 Translational Research Institutes and Programmes

India is transitioning into a nation with government-funded research parks. Under the
‘Make in India’ initiative, the Government of India has been actively considering the
establishment of four medical device parks to be set up in Andhra Pradesh, Telangana,
Tamil Nadu, and Kerala. Further details on this initiative are shown in Fig. 2.9. These
parks will provide the necessary infrastructure for research, while facilitating easy
access to standard testing facilities, and manufacturing of high quality, yet affordable
medical devices. The facilities are expected to include component testing centres,
biomaterial/biocompatibility testing centres, engineering design, and 3D printing
2.2 India’s Healthcare Initiatives and Translational Research Facilitation 41

Medical Devices: Target

Segments for Medical
Park Scheme

Implants and
Radiology and AnestheƟcs, implantable
Cancer Imaging Medical Cardio-respiratory electronic devices
Care/radiotherapy Devices including and Renal care like Cochlear
medical devices Nuclear Imaging medical devices Implants and
devices
Pacemakers

Fig. 2.9 Key device and implant segments that are being targeted by the Government of India’s
Medical Park Scheme (Source www.MansukhMandaviya.in)

facilities for medical grade products, sterilisation, and toxicological testing centres.
The key device and implant segments that are being targeted are shown in Fig. 2.9.
The Indo-UK Institute of Health (IUIH) had discussed the idea of 11 med-cities
with the Indian government in 2015. The med-cities were intended to be built in
Punjab, Gujarat, Andhra Pradesh, Rajasthan, Karnataka, Uttar Pradesh, West Bengal,
Maharashtra, Madhya Pradesh, Haryana, and Telangana. The institute is partnering
with medical technology companies, which will be carrying out manufacturing at the
med-cities. Each med-city was intended to contain a centre of excellence in a single
area of expertise. However, as previously discussed, it appears that the government
is more interested in comprehensive and self-sufficient facilities, rather than those
specialising in particular areas. An overview of the ‘Make in India’ Initiative is shown
in Fig. 2.10.

2014, Sept to Oct: Launch of the Make in India iniƟaƟve, focusing on 25 sectors, including medical devices
and a task force was consƟtuted to idenƟfy challenges pertaining to the development of high end medical
devices

2014, Dec.: The medical device market was built out from pharmaceuƟcal sector, enabling 100% of FDI
on the automated route, for brownfield and also greenfield set-ups.

2015, Apr.: 4 major states to set up medical device parks, to create an ecosystem for the
manufacturing of high end medical device products locally

2016, Jan.: Recommended increase in import duty and withdrawal of certain customs duty
exempƟons for such medical devices planned to facilitate domesƟc output

2017, Jan.: Medical Devices RegulaƟons and established a risk-based classificaƟon of medical devices.

2020, Apr: Regulated 23 classes of medical devices under CDSCO and NPPA; claimed that all medical devices
are controlled by the provisions of the Drugs, order 2013

Fig. 2.10 Make in India Initiative—for supporting the Indian manufacturing ecosystem (Source
Market Study of Advanced Ceramics and Composites in the Healthcare Space, Frost and Sullivan,
2020)
42 2 Economic Impact, Healthcare Initiatives …

Of the established research initiatives, IKP Trust is a major contributor to India’s

research output. Under the Startup India Initiative for Higher Education Institutions
(SIIHEI), the establishment of five new research parks is underway (IIT Delhi, IIT
Kanpur, IIT Guwahati, IIT Hyderabad, and IISc Bangalore) and continued funding
for two already approved research parks (IIT Kharagpur and IIT Bombay) is ongoing.

On the research facilitation frontier, Kalam Institute of Health Technology and

the Andhra Pradesh MedTech Zone are notable examples in India.

The participation of academia is indeed important in all such national initiatives.

The Healthcare Technology Innovation Centre (HTIC) is an example of an existing
centre established by academia and the government. Located at the Indian Institute of
Technology Madras Research Park, Chennai, HTIC is an initiative of Indian Institute
of Technology Madras (IITM) and Department of Biotechnology (DBT), Govern-
ment of India. HTIC collaborates with leading medical institutions and a range of
industry players and facilitates the collaboration of technologists, engineers, doctors
and healthcare professionals, industry and the government.
The Translational Health Science and Technology Institute, THSTI, is an impor-
tant example of a translational research ecosystem in a national institute in
India.

Established in 2009, THSTI undertakes research in biotechnology solutions

for highly prevalent human diseases in India in the areas of infection and
immunology, maternal and child health, non-communicable diseases, and
multidisciplinary clinical and translational research.

Several clinicians are involved in research at THSTI. The objective of connecting

academia with THSTI is to combine engineering sciences with biological sciences.
This would facilitate the framing of clinically relevant strategies to develop mate-
rials for implant and drug delivery applications, followed by clinical trials and
commercialisation.

2.2.2 Kalam Institute of Health Technology and the Andhra

Pradesh MedTech Zone

Kalam Institute of Health Technology (KIHT), Visakhapatnam, was set up as a

society under the Department of Biotechnology, Government of India, in 2017
(https://kiht.in/). KIHT’s mandate is to facilitate focused research on critical compo-
nents pertaining to medical devices by supporting stakeholder institutions engaged in
2.2 India’s Healthcare Initiatives and Translational Research Facilitation 43

development and promotion of healthcare technologies. KIHT has a unique e-auction

platform for accumulating healthcare technologies across the country and creating a
repository technology bank and facilitating transfer of such technologies/prototypes/
intellectual property to interested manufacturers and incubators.
AMTZ is a 270 acre-zone for medical device manufacturing. KIHT is located in
the AMTZ campus.

The AMTZ group of institutions is the only comprehensible model in India

providing innovation support, testing, validation, and manufacturing infras-
tructure along with policy support in health technology sector, within one
ecosystem.

After its inception, AMTZ held several domestic and international investor meets
to promote domestic manufacturing and awareness about the immense growth
opportunity that the medical device sector offers.
KIHT provides research and development support, market intelligence and trade
support as well as market access support. AMTZ’s Centre for MedTech Innovation
and Rapid Prototyping is designed to provide further support to researchers for devel-
opment of prototypes, including customisation and design. It contains a 3D printing
facility, to cater to start-ups, medium-scale and small-scale enterprises as well as
manufacturing sectors. The advantages of the 3D facility are mass customisation,
supply chain simplification and waste reduction.

KIHT/AMTZ’s facilities include the centre for gamma irradiation, biomaterials

testing facility, pre-clinical facility and animal house, electromagnetic compat-
ibility (EMC) testing, electromagnetic interference (EMI) testing, and acoustic
facility.

The gamma irradiation facility set-up at AMTZ with cobalt source supply from
BRIT/BARC would cater 15% (INR 4500 crores) of medical device market. A multi-
purpose plant was designed as per the guidelines of the Atomic Energy Regulatory
Board (AERB).
AMTZ is also a site for incubation of start-up companies. KIHT is the official
policy body for all departments of government for all health technology avenues.
MediValley, funded by NITI Aayog, the Planning Commission for the Government
of India and BioValley, funded by the Ministry of Science and Technology are world-
class incubators, representing the largest incubator ecosystem in the country in the
realm of healthcare technology.
44 2 Economic Impact, Healthcare Initiatives …

MediValley handholds innovators along all stages, from ideation to manufac-

turing while allowing full access to the AMTZ group of institutions.

The Fourth Global Forum on Medical Devices, organised at AMTZ in December

2018, was dedicated to discuss standards, regulatory framework, and medical access.
In order to bring together mentors, financiers, distributors, insurers, and all stake-
holders together for medtech start-ups, AMTZ hosts a quarterly start-up day in collab-
oration with the Confederation of Indian Industry (CII). AMTZ held a joint workshop
on 3D bioprinting with think3D in May 2019, which featured speakers from reputed
Australian and Indian institutions.
AMTZ was cited at the World Economic Forum 2019, Switzerland, as being a
sector-specific innovation cluster of global excellence. Such clusters enable govern-
ments to plan training programmes in collaboration with local industry and academia.
In April 2019, AMTZ hosted a workshop on medical devices and diagnostics for the
SEARN. In May 2019, a workshop on medical device regulation and certification
in the USA and Europe was held, thereby enhancing the knowledge of these promi-
nent regulatory systems in India. KIHT-AMTZ have 4 international MOUs, and 93
memberships in various national and international bodies.
The Make in India leadership institute (MIILI) programme, offered by KIHT, is
a rigorous executive programme of three weeks duration for working professionals
and exceptional graduates in the medical technology field. The course covers knowl-
edge in several thematic areas in medical devices: regulation, financing, pricing,
market access, R&D, and standardisation. The course broadly offers content of seven
modules, apart from activities like a medical technology industrial tour, webinars
by renowned international faculty members and a leadership session by an eminent
industry champion.
KIHT-AMTZ launched a novel Patent Academy, which offers a wide range of
Intellectual Property Rights (IPR) courses designed exclusively for students, IP
career seekers, researchers, entrepreneurs, and industry segments. In another initia-
tive, biomedical practitioners are encouraged to take the Indian Biomedical Skill
Certificate (IBSC) test, established by AMTZ and supported by the Quality Council
of India (QCI) and the Association of Indian Medical Devices Industry (AiMeD).

2.2.3 NITI Aayog and the National Health Stack

The Ayushman Bharat Yojana is a national programme designed to establish

1.5 lakhs of health and wellness centres for comprehensive primary healthcare
offering preventative and promotive healthcare accessible to all.
2.2 India’s Healthcare Initiatives and Translational Research Facilitation 45

The second arm of the Ayushman Bharat programme is the Pradhan Mantri-
Rashtriya Swasthya Suraksha Mission (PM-RSSM), which will cover more than 10
crores of poor and vulnerable families providing coverage of up to 5 lakhs per family
per year for secondary and tertiary care hospitalisation. The design of the Ayushman
Bharat Yojana was released in the Union Budget of the fiscal year of 2018–2019 and
is expected to be mediated by the states of India.

The National Health Stack (NHS) is conceived as a digital infrastructure

for implementing health initiatives, such as managing health data, managing
coverage and claims, and enabling patients to access their own health data and
national health analytics.

The platform could help to improve process flows for service providers. Other
potential building blocks include policy repositories, national level registries, work-
flows, incentivised access to stakeholders through open application program inter-
faces (APIs) and consolidation of all insurance and assurance claims for healthcare
at all levels (primary, preventive, secondary, and tertiary). The NHS is expected to
ensure deployment of patient-centric policies.
The current Indian healthcare system is lacking in standard treatment guidelines.
There is a need to create consistent and routine clinical processes with accountability
structures and measurable improvements in quality of care, focusing on patient safety,
comfort, satisfaction, and clinical outcomes. Therefore, the data systems should
ensure monitoring and verification of processes and patient outcomes.
Dexterity, flexibility, and evidence-based smart policy making are required for
the implementation of healthcare initiatives, such as the NHS in India, which is a
digital framework usable by centre and state across public and private sectors. The
initiative of the NHS is expected to be a technology-informed model for universal
health coverage, enabling cost-effective healthcare for all. The programme aims for
digital health records for all citizens by 2022.

Through the NHS, NITI Aayog is intending to shape strategic policy actions
to improve health security by operating in mission mode, what would be the
largest healthcare programme in the world.

The NHS would draw from big data analytics, machine learning, and artificial
intelligence. Therefore, NHS in India is perceived to be the best-in-class healthcare
information technology system.
46 2 Economic Impact, Healthcare Initiatives …

2.3 Education and Human Resources

Education and human resources are key to the success of any translational research
initiative. The Indian medical devices industry has not operated like those of the
established economies of developed countries. In the developed country model,
the companies employ the most expensive talent, such as the best engineers and
researchers, and then recover the money via end product pricing and selling to insur-
ance companies. In India, the talent available is variable in quality and the recipients
of the service are small Indian companies, who often cannot afford to pay a high
salary to many of their manpower.

With the anticipated growth of the Indian market, there is a distinct need to
revamp the bioengineering and medical curricula in academic institutions.

With a view of attracting bright and meritorious students to research, the Prime
Minister’s Research Fellows (PMRF) Scheme has been launched recently. The
scheme seeks to admit meritorious students into PhD programmes at IITs, IISc,
and IISERs. These scholars receive fellowships, which are comparable or better than
those of graduate students in the USA or other western countries. More than 200
fellows have been admitted to the scheme so far.

2.3.1 Bioengineering Curriculum and Indian Academia

At the backdrop of the accelerated growth of the field of biomedical engineering

in the western world, this interdisciplinary field is growing both in the context of
academic curriculum and translational research.

Many universities around the world have already started new interdisciplinary
academic programmes namely, under the titles on ‘biological engineering’ or
‘bioengineering’ or ‘biosystems science and engineering’ or ‘medical science
and technology’ or ‘clinical engineering’.

Such academic programmes will provide a comprehensive platform for

researchers from multiple disciplines to interact while collaborating to share compli-
mentary expertise. On the brighter side, this practice is followed in some IITs and
a few schools in India. However, currently in India, there is a dearth of widespread
initiatives in academia like study programmes and training of young researchers in
the area of biomaterial sciences. Hence, many students lack the knowledge about the
2.3 Education and Human Resources 47

fundamental concepts of biomaterial sciences, which can be a bottleneck to pursue

research in this area.
It has been widely perceived nationally that undergraduate/postgraduate studies
in biomedical engineering (BME) or similar disciplines still do not attract the best
students. This can be largely attributed to, (a) poor job market in India, (b) lack
of fundamental concepts in undergraduate courses as well as common curriculum
of BME and (c) lack of integration among the stakeholders, national laboratories,
hospitals, industries, and universities/IITs/IISc. The current employment for many
undergraduate students of BME is seen in non-technical areas, like customer support,
sales and services, maintenance, and management of imported healthcare equipment.
Also, many undergraduate students of BME opt for higher studies in the field of
bioengineering, abroad.
Considering the increasing importance of high-quality manpower in the healthcare
sector, a new Graduate Aptitude Test in Engineering (GATE) paper in biomedical
engineering was introduced and has been effective from 2020 for screening of under-
graduate students before they can be admitted to postgraduate programmes in India.
It is envisaged that this initiative will enable the academic institutes to modify the
course curriculum to introduce a problem-solving/analytical approach at the intersec-
tion of biology, medicine, and engineering. Also, more focus is expected to improve
skills in the areas of anatomy, physiology, molecular biology, and human–machine
interface, etc.

2.3.2 Medical Education and Research in India

Progress in the field of biomaterials science and implants can be accomplished

only with commensurate progress in medical education and the clinical research
ecosystem.

In 2017, there were 479 medical colleges in India, with admission capacity of
over 60,000 at the undergraduate level.

The Medical Council of India (MCI) is the government-mandated regulatory

agency for medical education. The total admission capacity for postgraduate medical
degrees is about 8684 in MS, 16,195 in MD, 1280 in MCh, 1420 in DM, and 3837
in various diploma disciplines.
The doctor—population ratio varies from state to state with unequal distribution
between rural and urban areas. The challenge of promoting a spirit of dedication for
serving rural areas among medical graduates is still being faced. The World Health
Organization’s South-East Asia Regional Office in conjunction with Reorientation of
Medical Education (ROME) suggested that to solve this problem, the medical educa-
tion community, including residents, interns, and students should be oriented to the
48 2 Economic Impact, Healthcare Initiatives …

conditions existing in rural communities and that training in management of health

problems in these areas should be provided. The scheme aimed to render compre-
hensive healthcare in villages in collaboration with the concerned primary health-
care centres. Each medical college was to establish a well-knit rural referral system,
engage in outreach activities, post medical students in the community, provide mobile
clinics, and stimulate the entire faculty to conduct community-based training.
In order to improve the distribution of research capabilities across the nation,
ICMR has given substantial funds to 100 medical colleges in India towards research
and have also started funding small ICMR research units across the country with
instrument and manpower support. Also, research funding organisations are spending
10% of their budget to develop research infrastructures in North-Eastern states of
India. The medical universities or national institutes of importance, like AIIMS can
significantly contribute to research on biomaterials and implants, by providing the
ecosystem for better interaction with researchers from academia and for conducting
pre-clinical and clinical studies. The academic researchers would be largely benefited
from regular interactions with clinicians or clinical scientists and would gain insights
into the clinical relevance of a given research problem.

Although conducting randomised controlled trials (RCTs) would be advanta-

geous financially, research capability and reputation of institutions, rules and
regulations associated with conducting an RCT are very restrictive.

Another important issue that is raised is the paucity of primary healthcare physi-
cians, coupled with the excess of specialists—an imbalance that needs to be corrected.
The MCI has recently developed guidelines and regulations pertaining to the estab-
lishment of new medical colleges, the opening of higher cases of study, and a greater
control of admission to medical colleges. Nevertheless, with the sudden increase in
private medical colleges, there has been a concern regarding the quality of education
and also issues with maintaining a part of the teaching approaches relevant to rural
community constraints. Also, it is a current challenge that medical students should
be more able to respond to local health problems and the related social, cultural, and
economic factors, by meaningfully applying knowledge and analysing facts.
Regarding quality of teaching, there are inadequate opportunities for teacher
training and orientation, and lack of incentive structures to recognise and reward
teaching effort. A group of medical schools in the country led by four leading insti-
tutes has organised a Consortium of 20 medical colleges for undertaking innovative
projects in medical education. The Consortium has established a collaboration with
the Department of Medical Education, University of Illinois, Chicago, USA.

The leading institutes in clinical research are All India Institute of Medical
Sciences (AIIMS), New Delhi; Institute of Medicine, Banaras Hindu University
2.3 Education and Human Resources 49

(BHU), Varanasi; Christian Medical College, Vellore; and Jawaharlal Institute

of Postgraduate Medical Education (JIPMER), Pondicherry and, Postgraduate
Institute of Medical Education & Research (PGIMER), Chandigarh.

The Consortium plans to conduct advanced courses for a Fellowship in Medical

Education Scheme, in order to develop educators that will lead educational changes
in India. The MCI has recognised 10 nodal centres for this purpose. Also, the points
raised at the Edinburgh Declaration of the World Federation for Medical Education
have been fully endorsed at the national level. There has been a suggestion for the
planned constitution of a Medical Education Commission, and also the MCI has
recently attempted to develop a needs-based curriculum. Revision of the rules and
regulations governing undergraduate and postgraduate education are underway by
the MCI. In future, it is expected that the National Medical Commission will guide
medical education and healthcare in India.

There exists an unmet need to revamp the medical and bioengineering curricula
and research ecosystem in India, and a similar situation prevails in many
developing nations.

In this context, the importance of key roles in building research teams has been
highlighted by the Stanford University Biodesign Leadership Programme in their
review of the first twelve years of the programme. Four personality profiles of highly
functional teams were highlighted, and these are the builder, who is responsible for
design and prototyping, the organiser, who monitors progress, the researcher, who
will distil information from the body of clinical, engineering and business litera-
ture and the clinician, who understands the complex issues associated with intro-
ducing a new technology into clinical practice. It is hoped that such schemes will be
considered, while introducing new medical education and research policies in India.

2.4 Funding Status and Opportunity

2.4.1 National Funding Schemes

This section highlights the status of funding opportunities for basic research and
translational programmes in the area of biomaterials science and implants funded by
the Government of India.
50 2 Economic Impact, Healthcare Initiatives …

2.4.1.1 Ministry of Science and Technology Funding

In India, the research on biomaterials science, biomedical engineering, or

bioengineering-related areas is significantly funded by the federal agencies, such
as the Department of Science and Technology (DST), Science and Engineering
Research Board (SERB), and Department of Biotechnology (DBT), and the Indian
Council of Medical Research (ICMR). In addition, CSIR, DRDO and DAE also fund
such research activities mostly to the scientists, who are working at the national labo-
ratories affiliated with the respective organisations, and the academic researchers, in
the form of extramural grants to a much less extent (quantum of funds for bioengi-
neering). DRDO has a Life Science Research Board (LSRB), which administers
funding related to bioengineering areas.
Two different panels of SERB, i.e. Materials, Mining & Minerals Engineering;
and Biomedical and Health Sciences panel, regularly invite proposals, fund a few
selected projects, and also administer their progress. According to data received from
the DST-materials panel, a total of 28 projects, worth Rs. 12.8 crores (≈1.8 million
USD) were funded in the timespan of 2014–2019. These projects are largely on
biomaterials development with a focus on advanced manufacturing, microstructure-
property correlation and biocompatibility of Mg-based biodegradable alloys, Ti-
based alloys (e.g. Ti6Al4V), bioceramics/bioglasses, and biopolymers/natural silk-
based scaffolds. The outcomes of the funded projects were able to address some of
the existing clinical challenges in orthopaedics, dentistry, cartilage regeneration, and
neurosurgical treatment.
A similar review of funding from DBT revealed an impressive total of Rs. 40.8
crores (≈5.9 million USD) for research projects related to biodesign, bioengineering,
or biomedical engineering-related areas over 2014–2019 (Fig. 2.11). Among these
projects, several projects, particularly related to biomaterials and related devices,
were worth of 23.5 crores (~3.4 million USD). All these projects are aligned with
DBT’s mandate to facilitate, a) medical technology (medtech) innovation in India,
b) entrepreneurship and research leadership in biomedical engineering, c) medtech
products across larger cross-section of Indians with broader affordability, and d)
translational research involving multidisciplinary teams (clinicians, researchers from
academia/national laboratories and industry).

2.4.1.2 Biotechnology-Focused Funding

The biotechnology sector is recognised as one of the key drivers for contributing
to India’s economy target of 5 trillion USD by 2024. The Indian biotechnology
sector is poised to grow exponentially over the next decade. India is among the top
12 destinations for biotechnology in the world, valued at 51 billion USD during
2018–19.
2.4 Funding Status and Opportunity 51

Fig. 2.11 Funding of research programmes on biomaterials and implants by the Government of
India under several schemes monitored by DST and DBT

The major policy initiatives of the Government of India (GoI), such as the Make
in India programme are aimed to develop India as a world-class biotechnology
innovation and biomanufacturing hub.

The Biotechnology Industry Research Assistance Council (BIRAC) is a not-

for-profit public sector enterprise, set up by DBT, to strengthen and empower the
emerging biotech enterprise to undertake research and innovation to address product
development needs of national importance (https://www.birac.nic.in/). BIRAC
implements a wide range of initiatives, such as providing access to risk capital,
targeted funding, technology transfer, IP management, and handholding schemes
that help bring innovation excellence to biotech firms.
There are several schemes of BIRAC/DBT, intended for different sectors.
BIRAC’s BIG scheme is intended for researchers/innovators in the area of biotech-
nology, who want to be entrepreneurs. The aim of this scheme is to provide
support for proof-of-concept research. BIRAC has collaborated with the Society
for Research and Initiatives for Sustainable Technologies and Institutions, Ahmed-
abad (SRISTI) for the BIRAC-SRISTI GYTI awards, which are intended to nurture
15 entrepreneurial ideas every year for two years.
52 2 Economic Impact, Healthcare Initiatives …

The Small Business Innovation Research Initiative (SBIRI) scheme of the

DBT is an enabling platform for the target organisations to realise their poten-
tial in terms of product and process development and taking products and
technologies to the market.

The Biotechnology Industry Partnership Programme (BIPP) is a government part-

nership with industries on a cost-sharing basis for path-breaking research in fron-
tier futuristic technology areas, having major economic potential, including Devices
& Diagnostics. BIRAC’s Promoting Academic Research Conversion to Enterprise
(PACE) programme is intended to encourage and support academia to develop a
technology or a product of national importance up to proof-of-concept stage and
subsequently have it validated by an industrial partner.

The BIPP programme has the Academic Innovation Research (AIR) scheme
to promote the development of proof of concept for a process or product by
academia with or without the involvement of industry.

Alternatively, the Contract Research Scheme (CRS) aims at validation of a process

or prototype (developed by academia) by an industrial partner.
Other than funding, BIRAC also provides support to innovators via the SPARSH
programme (Social Innovation programme for Products: Affordable & Relevant to
Societal Health). This scheme aims to create and foster a pool of social innovators
(‘SIIP Fellows’) in the field of biotechnology and to provide a platform to share the
best practices, understand the complex intricacies of business models in social inno-
vation and network. BIRAC’s Sustainable Entrepreneurship and Enterprise Develop-
ment Fund (‘SEED Fund’) assists start-ups by providing capital assistance to start-ups
with novel and worthy ideas, innovations and technologies. This would enable some
of these start-ups to advance to a level, where they will be able to raise investments
from Angel/Venture capitalists or to reach a position to seek loans from commercial
banks/financial institutions.
The proposed seed support is intended to act as a bridge between promoters’
investment and Venture/Angel investment. Also, available is the Accelerating
Entrepreneurs (AcE) fund, intended to support start-ups.

BIRAC together with the National Biopharma Mission has initiated a tech-
nology transfer and commercialisation training programme, intended to
strengthen overall capacity in the country in technology transfer.

In the last few years, a number of funding initiatives, in parallel to federal

funding schemes, have come into the forefront to facilitate translational research
2.4 Funding Status and Opportunity 53

in the biomedical engineering domain. One of them, is the Innovation, Knowledge,

Progress (IKP) Trust, IKP. IKP is one of the six implementing partners of the Biotech-
nology Ignition Grant, supported by BIRAC (https://www.ikpknowledgepark.com/
ikp-group.html).

The IKP trust has funded 300 start-ups and innovators, out of which 180 have
been grant- or seed- funded, and 160 have been incubated, with 16 mergers
and acquisitions being completed.

More than 7000 jobs have been directly created and 25,000 jobs have been
indirectly created through all these entrepreneurial activities. IKP Trust has three
programmes in its national footprint—IKP Knowledge Park, IKP Ventures, and IKP
EDEN.
Within the IKP framework, a number of hubs or research parks are being estab-
lished. The Science Park, Hyderabad, has a 200 acre campus with a 50,000 ft.2
SME hub and 10,000 ft.2 Life Science Incubator. The Life Science Incubator has
been host to over 65 start-ups. It provides modular laboratory space, common equip-
ment, funding and mentorship, legal and IPR support and facilitates networking
among different incubators. In Karnataka, BioNEST is a MedTech Incubator in
Bengaluru, and K-tech innovation hubs have six prototyping centres. IKP Knowledge
Park manages several pan-India grants, with a total of 130 crores INR of funding.
IKP Ventures manages an Indian innovation fund, which is currently dedicated to
healthcare. IKP Engineering, Design and Entrepreneurship Network (EDEN) has
a 25,000 ft.2 hardware incubator and makerspace in Bengaluru for all streams of
industrial design, which currently hosts over 80 start-ups. IKP EDEN has prototyping
facilities for several applications, including medical devices.
IKP Knowledge Park’s Grand Challenges Exploration (GCE) India Programme,
in collaboration with BIRAC and the Bill and Melinda Gates Foundation, is designed
to inspire out-of-the-box innovative ideas on high-priority global health issues, with
funding of $100,000 USD for 18 months per project. IKP has an SME Hub at Hyder-
abad, operational from late 2019, mandated to provide 50,000 ft.2 of wet laboratory
space, 31 laboratory modules, and shared instrumentation facilities. In 2018, the
GCE-India programme funded seven such programmes, two of which are in the areas
of urological implants to treat bladder carcinoma and paper-based micro-fluidics for
diagnostic purpose.

2.4.1.3 Recent Funding Schemes on Societally Relevant Areas

The Government of India has felt the persistent need to make the research in
India more focused on the needs of society. Several schemes have been launched,
such as Unnat Bharat Abhiyan, Rashtriya Avishkar Abhiyan, Uchchatar Avishkar
Yojna, Pandit Madan Mohan Malaviya National Mission on Teachers and Teaching,
54 2 Economic Impact, Healthcare Initiatives …

Swayam, and Global Initiative for Academic Network. The Science and Engi-
neering Board, SERB, has launched ‘SERB-SUPRA (Scientific and Useful Profound
Research Advancement)’ for scientists working in realms of highly unconventional
pathways of transformative research, which may possibly lead to new hypotheses or
challenge existing ones and provide innovative solutions.
Among various national initiatives, those of great importance discussed here are
Uchchatar Avishkar Yojna (UAY), IMPacting Research Innovation and Technology
(IMPRINT), and Scheme for Promotion of Academic and Research Collaboration
(SPARC). UAY was launched in October, 2015 with an aim of promoting innovation
of a higher order that directly impacts the needs of industry and thereby improves
the competitive edge of Indian manufacturing. In UAY-I and –II, 84 and 64 projects
were sanctioned for Rs. 254 crores (36 million USD/27 million GBP) and 135 crores
(19 million USD/14 million GBP), respectively.

The Impacting Research Innovation and Technology scheme (IMPRINT) was

launched by the Government of India in 2015 to provide solutions to the most
relevant engineering challenges and to facilitate translating knowledge into
viable technologies in 10 selected domains, including Advanced Materials and
Healthcare.

An initiative of the Ministry for Human Resource Development (MHRD) and the
Department of Science and Technology (DST) (https://imprint-india.org/), the aim of
IMPRINT is to bridge the gap between the scientific knowledge base created through
fundamental/applied research and enable translation of the research through engi-
neering invention and technological innovation for national benefit. The domains that
are relevant to biomaterials and bioengineering are healthcare technology, advanced
materials, and nanotechnology. Notably, for this scheme, financial support from
industry is necessary. The average funding for approved projects is around Rs. 2
crores per project (277,490 USD/227,290 GBP), and in 2018, 123 projects were
sanctioned. In IMPRINT-I and –II, 142 and 126 projects were sanctioned for Rs. 313
crores (33 million USD/12 million GBP) and 112 crores (16 million USD/12 million
GBP), respectively.
The Scheme for Promotion of Academic and Research Collaboration (SPARC)
is an initiative of the Indian government, started in 2018 (https://sparc.iitkgp.ac.in/
index.php). This initiative was based on the thought that the maximum benefit of
a collaboration can be harvested only when the Indian research group, particularly
the young researchers, can be trained at world-class research facilities in top inter-
national research groups. It funds long-term visits by the international faculty (2 to
8 months) and also funds the travel and sustenance of Indian students at one of the
top 500 globally reputed universities/institutes. The programme aims to increase the
number of highly trained scientific manpower in the country, and to promote Indian
science and scientists in the world. The thrust areas in SPARC that are relevant to
2.4 Funding Status and Opportunity 55

biomaterials and bioengineering, are affordable healthcare (convergence), nanotech-

nology, biotechnology and applications (innovation-driven), and design innovation
(innovation-driven). Funding offered per project is in the following categories: up to
Rs 50 lakhs, from Rs 50 lakhs up to Rs 75 lakhs, and from Rs 75 lakhs up to Rs 100
lakhs (100 lakhs is equivalent to 138,730 USD/113,639 GBP).

2.4.2 International Status

It would be interesting to briefly assess the funding status in the USA, UK, and
other developed nations. The Engineering and Physical Sciences Research Council
(EPSRC) is the main funding body for engineering and physical sciences research in
the UK (https://epsrc.ukri.org/). The Biomaterials and Tissue Engineering Research
Area constitutes 1.1% of the total EPSRC portfolio. The funding allocated for the
area is £65.5 million (approx. 576 crores INR) for a total of 95 grants. The Euro-
pean Union’s Horizon 2020 (2014–2020) research and innovation programme is
another scheme, which funds projects in the area of biomaterials and bioengineering.
Under the work programme 2018–2020—Future and Emerging Technologies (EUR
183.5 million, i.e. INR 1,524 crores for 2018–2020), the relevant area is ‘Disrup-
tive technologies to Revolutionize Healthcare’. Another relevant area, is ‘Advanced
Materials’ under ‘Key Enabling Technologies’.
The European Research Council (ERC), which funds research in the EU affiliated
countries, has recently started a new initiative to fund ‘frontier research’ programmes
(https://erc.europa.eu/). In general, the funding schemes of the ERC are tailored to
different stages of the investigator’s career, such as ERC starting grants, for early
career researchers with 2–7 years’ post-PhD experience, ERC consolidator grants
for researchers with 7–12 years’ post-PhD experience, and ERC advanced grants for
established research leaders with a proven track record of research achievements. The
maximum values of these grants range from e1.5 to 2.5 million for up to 5 years, the
Indian equivalent being 12.42–20.7 crores INR. One can perceive that by categorising
the levels of experience and achievements of the investigators, the ERC is enabling
more of a level playing field among researchers over a wide spectrum of experience
in science. Other grant schemes include the ERC Proof of Concept and the ERC
Synergy Grants, of which the latter is for a team of up to four PI’s groups.

The USA’s National Institutes of Health (NIH) is the largest public funder of
biomedical research in the world, investing more than $32 billion USD a year.

The National Science Foundation with an annual budget of about $7.8 billion USD
(INR 58,888 Crores) funds research through grants and cooperative agreements to
more than 2,000 colleges, universities, K-12 school systems, businesses, informal
science organisations, and other research organisations throughout USA. The NSF
56 2 Economic Impact, Healthcare Initiatives …

has a Division for Materials Research, of which there is a Biomaterials Group.

Of relevance also is the Cellular and Biochemical Engineering (CBE) programme
under the Engineering Biology and Health Cluster (Directorate for Engineering). The
programme includes Disability and Rehabilitation Engineering, and Engineering of
Biomedical Systems. An example of a relevant project grant is $533,338.00 (~INR 4
crores) for research on polymer therapeutics for bone regeneration as next-generation
osteoporosis treatments.
The National Institute of Biomedical Imaging and Bioengineering is an organ-
isation of the National Institute of Health, whose mission is to improve health
by leading the development and accelerating the application of biomedical tech-
nologies. The Division of Discovery Science & Technology (bioengineering) is
particularly relevant and the organisation is responsible for research funding.
In Australia, the Medical Research Future Fund (MRFF) was set up by
the Australian Government in 2015 (https://www.health.gov.au/initiatives-and-pro
grams/medical-research-future-fund).

From the MRFF fund, $190.8 million (equivalent to 893 crores INR) are being
invested in clinician researcher fellowships, in Australia.

The scheme covers key clinical areas and pays for the salaries of the clinicians, if
required, and a research support package for 5 years. Under the Australian Govern-
ment’s Medical Research Commercialisation Initiative, delivered by MTPCon-
nect, the $45 million AUD (equivalent to 210.7 crores INR) BioMedTech Hori-
zons programme supports research programmes involving innovative health tech-
nologies and medical devices through their journey from discovery towards proof
of concept and commercialisation (https://www.mtpconnect.org.au/biomedtechho
rizons). Under this specific scheme, the funding for each project can be typically of
up to $1 million (4.6 crores INR). As per the National Critical Research Infrastruc-
ture initiative of the Australian Government, funding will be provided for research
infrastructure needed for conducting health and medical research.

2.5 A Way Forward

Against the backdrop of the significant socio-economic potential, it is important to

establish capabilities of indigenous biomaterials and biomedical implants manufac-
turing. Towards achieving this longstanding need, it is indeed imperative for a national
policy to promote establishing of medtech research parks in India. This would
change the ecosystem of the highly import-dependent medical devices segment. This
includes not only providing resources for medtech start-ups and indigenous manu-
facturers, but also providing them with support for the commercialisation, intellec-
tual property, and regulatory aspects. The funding for research programmes in this
2.5 A Way Forward 57

direction is certainly not substantial, when compared to the current status in many
developed nations. Furthermore, it is essential for a trained workforce to be in place
for the medical parks to be a success. This needs revamping the medical education
system as well as introduction of bioengineering programmes in more institutes of
national importance.
It can be perceived that translational research needs to have a greater impact in
India, so that the outcome can be translated to the commercialisation of indigenously
developed products and technologies in the medtech market. This should be pursued
without compromising the quality in terms of clinical performance of the devices
and implants. The far-reaching impact of implementing a more robust ecosystem
can therefore be very significant in terms of the patient’s well-being in the world’s
second largest populous country (India), and this will be a model for other developing
nations.
Chapter 3
Scientists at Work in India

Abstract As breakthroughs in biomaterials science reach a tipping point, a tour

de force of the diverse research in laboratories of excellence across India can be
seen to occur, promising lower healthcare costs and a better future for patients.
Who are the scientists, what are they up to and where? The rise of engineering
and advances in biology opened up new frontiers in the twentieth century. In the new
millennium, as the two started to converge, biomaterials sciences took shape, creating

Disclaimer: The presentation of material and details in maps used in this chapter does not imply
the expression of any opinion whatsoever on the part of the Publisher or Author concerning the
legal status of any country, area or territory or of its authorities, or concerning the delimitation of its
borders. The depiction and use of boundaries, geographic names and related data shown on maps
and included in lists, tables, documents, and databases in this chapter are not warranted to be error
free nor do they necessarily imply official endorsement or acceptance by the Publisher or Author.

© Springer Nature Singapore Pte Ltd. 2020 59

B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0_3
60 3 Scientists at Work in India

an unprecedented link amongst engineers, biologists, clinicians and entrepreneurs.

Numerous initiatives are underway at the national and institutional levels in India,
with a number of research groups working in academia and national laboratories
(see geographical map and groups). However, challenging barriers exist between the
bench and bedside; as many research programs are ended at late stages of laboratory-
scale development or pre-clinical validation. A few examples from the academia and
national laboratories will be provided to highlight the status of the clinically validated
indigenous technologies. It is noteworthy that funding and facilitation are required
for human clinical trials, an important step in translational biomaterials science.
Therefore, significant challenges pave the road to this transformative partnership:
how to translate biomaterials and bioengineering concepts to improve human health?
Like every other branch of science, biomaterials science, too, does not exist in a
vacuum. This chapter portrays the Indian landscape of biomaterials science and
implants. The discussion in this chapter may not contain all the national groups, and
many of these have been currently pursuing important research themes in the field
of biomaterials and implants.

3.1 At the Tipping Point

Biomaterials science stands at the confluence of two contradictory forces. On the

one hand, there is the promise of the science that can meet the massive challenge of
high-quality public healthcare in India. On the other hand, there is the question of
cost-effectiveness that can be solved only by taking world-class scientific work from
Indian laboratories to the patient’s bedside, keeping in mind time, cost, quality, and
regulatory hurdles.

A handful of research groups are engaged in translational research—a concept

that describes scientific investigation, aimed at transferring laboratory discov-
eries into new methods for diagnosing, preventing and treating diseases, as
well as using the knowledge gained to improve healthcare policy.

I will discuss the work of scientists from many disciplines who often work in
collaboration across laboratories. Their research activities, funding status, commer-
cialisation efforts, and regulatory compliance reveal the landscape of this frontier
science in the country.
3.2 All About Joints: Hips, Knees and Spines 61

3.2 All About Joints: Hips, Knees, and Spines

CSIR-CGCRI scientists, over the last two decades, have developed new manu-
facturing technology to develop Al2 O3 -based ceramic femoral heads, ZTA-based
femoral heads, HA-based coatings for metallic implants, drug-eluting femoral stems,
HA/TCP-based granules for the clinical domains of orthopaedic and/or dental
surgery. An Al2 O3 -based ceramic femoral head has been developed by CSIR-CGCRI
for ceramic-on-PE total hip replacement (THR) and those femoral heads have under-
gone single centric clinical trials. They patented this technology for manufacturing
process for a modular Al2 O3 based ceramic femoral head, which can be fitted with
a standard hip stem, for THR surgery (see Fig. 3.1). The manufacturing technology
for depositing a crystalline hydroxyapatite coating on hip stem implants is also
being developed in the same CSIR laboratory. To obtain better adherent coatings, the
synthesis of hydroxyapatite powders has been tailored to ensure better flowability
during plasma spraying.

Most of the biomaterials or implants developed at of CSIR-CGCRI have been

validated in at least one single-centre clinical trial.

a b

Fig. 3.1. (a)–(c) Ceramic-on-Polyethylene implants for total hip joint replacement and (b) Plasma-
sprayed hydroxyapatite coating on metal hip implants, commercialised products developed at CSIR-
CGCRI, Kolkata (Images courtesy CSIR-CGCRI, Kolkata)
62 3 Scientists at Work in India

Life of a metal-on-plastic THA is often limited to 10 years, mainly due to excessive

wear debris generation during its operation, leading to aseptic loosening. Machining
of an extruded block of UHMWPE leaves some permanent marks on the commer-
cially available liner, which is also one of the reasons for severe wear debris genera-
tion. An Al2 O3 -based ceramic femoral head has been developed by CSIR-CGCRI for
ceramic-on-PE total hip replacement (THR) and those femoral heads have undergone
single centric clinical trials.
The author’s research group (earlier at IIT Kanpur and currently at IISc Bangalore)
has developed new biomaterials concepts and conducted biocompatibility assessment
on implants for musculoskeletal regenerative applications. In particular, their work
on three different generations of polymer-ceramic hybrid acetabular liner (total hip
replacement, also called total hip arthroplasty or THA), has resulted in new alter-
native biomaterials options. For acetabular liners, UHMWPE/HDPE blend-based
composites reinforced with surface functionalised graphene oxide (GO) were found
to effectively enhance mechanical strength, clinically desired wear resistance with
less wear debris generation and biocompatibility (see Fig. 3.2). The hybrid composite
has shown excellent bone regeneration, when implanted in rabbits’ femoral defect
for 12 weeks or in segments of tibia over 14 weeks post-implantation.

A new generation of polymer-ceramic hybrid acetabular liner has been devel-

oped using three different manufacturing routes by IIT Kanpur, IIT Guwahati,
and IISc Bangalore researchers.

Clinical Study Planned

Fig. 3.2 Polymer-Ceramic hybrid acetabular liner: Science-to-Product Prototype (research

conducted in author’s group at IIT Kanpur and IISc, Bangalore)
3.2 All About Joints: Hips, Knees and Spines 63

In particular, the collaboration between IISc Bangalore (Basu) and IIT Guwa-
hati (Kanagaraj) researchers has led to the development of an acetabular liner of
UHMWPE/MWCNT/nHA nanocomposite, with superior wear resistance, better
biocompatibility, and high surface finish, leading to improved longevity of the
metal-on-plastic prosthetic. Importantly, cost analysis for hybrid polymer-ceramic
composite-based acetabular liner implants, shows a 3–4 times lesser cost, when
compared to that of the imported ultra-high molecular weight polyethylene
(UHMWPE) liners.
Another collaboration between NIT Rourkela (Sarkar) and IISc (Basu) in the field
of orthopaedics resulted in patenting a new manufacturing technology for making
ceramic femoral heads.

While using an Integrated Computational Materials Engineering (ICME), the

team of researchers from NIT Rourkela (Sarkar) and IISc (Basu) judiciously
developed process protocols for femoral head prototypes of zirconia-toughened
alumina (ZTA) with reliable mechanical properties, including clinically rele-
vant burst strength, together with blood and tissue compatibility, in mouse
models.

Based on the outcome of the pre-clinical study, the ceramic femoral head, manu-
factured using a cost-effective route, has advanced into a human clinical trial
on osteoarthritic patients to obtain scientific evidence (clinical and radiological
outcomes) of the safety and efficacy in total hip replacement surgery.
Research at Kanagaraj’s group at IIT Guwahati is in progress on a multi-axes ankle
joint, direct socket fabrication system, knee brace for osteoarthritis patients, recip-
rocating gait orthosis, and a mid-face external distraction device. In particular, the
development of the polycentric knee joint (IITG Knee or SANKALP Knee) has gone
through three evolutionary stages, with each having gone through design improve-
ments and additional features to improve its functionality. The first two generations
were used by 12 trans-femoral amputees in India. The testing of orthopaedic devices,
like total hip or knee replacement implants demand the use of costly equipment, like
hip or knee joint simulator, respectively. Like many other scientific equipments, these
test facilities are mostly imported and are available in less than five places, including
academic institutions and national laboratories.

Kanagaraj and his team at IIT Guwahati developed an ISO standard hip joint
motion simulator with four degrees of freedom, for the first time in India. The
present version is a modular version of a simulator, which can be modified as
a knee joint simulator and intervertebral disc wear simulator.
64 3 Scientists at Work in India

Generation 1 Generation 2 Generation 3

Polycentric Knee Joint Clinical Trials (approved by IHEC, IITG and NEIGHRIMS, Shillong)

UHMWPE and UHMWPE/MWCNT

acetabular liners Multi-axes ankle joint Knee brace Suture mediated vascular
closure device
Biomedical devices for Assistive Technology

Hip joint wear Orbital Bearing Aneurysm (Fluoroscopy) Shape storage Shape recovery
simulator (ISO Machine (ISO 4D printed porous radiopaque shape memory polyurethane
14242-1) 14242-3) for endovascular embolization

Fig. 3.3 Overview of biomaterials or biomedical engineering research in Kanagaraj’s group at IIT
Guwahati (Images courtesy S. Kanagaraj)

The past and present research programs at the gait and motion analysis labora-
tory of IIT Guwahati, under the leadership of S. Kanagaraj, also focus on devel-
oping a knee brace for the conservative treatment of osteoarthritis, preservation
of residual hearing after fixing the cochlear implants, shape memory polymers for
endovascular application, bipolar forceps for electrosurgery, bone marrow aspira-
tion device, mid-face external distraction unit, and many more (see Fig. 3.3). His
recent work on the near-net shape manufacturing of a polymeric acetabular liner
based on UHMWPE-HA-MWCNT nancocomposites will now enter the pre-clinical
validation stage. Many of the biomaterials or biomedical device prototypes are also
being tested using in-house facilities, like the hip joint wear simulator, orbital bearing
machine, and amputee walking simulator (see Fig. 3.3).

3.3 Bones and Teeth

Novel dental implant designs and their clinical efficacy constitute major challenges
in the field of reconstructive dentistry.
3.3 Bones and Teeth 65

Naresh Bhatnagar’s research group at IIT Delhi has employed biomechanical

analysis, and adapted conventional manufacturing processes, to manufacture
metallic dental implants, which were marketed in India in late 2019.

The major highlights of the commercialised technology include: (a) simulation

of lobed implant screw; (b) manufacturing of designed implants and laboratory-
scale testing, including fatigue testing; (c) animal testing (cadaveric), and (d) limited
clinical trial.
In an ongoing research program, the author’s research group at IISc, Banga-
lore, has been working on the development of a complete three piece-dental implant
stem, made of implant screw, straight and angulated abutments with hybrid thread
profiles, locking screw, healing abutment, and cover screw. The work, conceived
in collaboration with a prosthodontist, Dr. Vibha Shetty, Ramaiah University of
Applied Sciences, Bangalore, has resulted in an indigenous dental implant system
to treat edentulism (see Fig. 3.4). Biomechanical compatibility has been demon-
strated by using extensive finite element analysis and chewing simulation studies.
The combination of sand blasting and acid etching, together with the introduction of
dual ceramic coatings (collaboration with SCTIMST, Thiruvananthapuram) on abut-
ment/screw surfaces with an asymmetric antirotation profile and clinically relevant
hybrid thread profile, are considered as inventive components in this new implant
system. This system exhibits better primary stability (insertion torque in synthetic

Remov
Inser al
-Ɵon
Sawbone

Porcine Human
Torque tesƟng machine
bone bone
CAD design of 3D model Virtual implantaƟon Finite Element Analysis InserƟon and removal torque test
Benchmarking against Threads

clinically used implant

CBCT Internal features

ISO
14801:2016
No appreciable damage and/or distorƟon
is noƟceable aŌer 1 million cycles at a
Sand-blasted/acid- Surface modified loaded dental wear simulator machine

etched surface Implant prototype FaƟgue test

Clinical Study
Planned
Clinically used implant surface
Pre-clinical study (rabbit condyle)

Fig. 3.4 Dental implant system with hybrid threads and antirotational features developed at DBT
sponsored translational centre of excellence on biomaterials (IISc-SCTIMST-Ramaiah University
of Applied Science collaboration)
66 3 Scientists at Work in India

and animal bone) and osseointegration in rabbit condyle, when compared to those
of the commercial implants.

The thread design of dental implants and their biomechanical validation to

assess periprosthetic bone response in a clinically acceptable manner consti-
tutes one of the major research themes in reconstructive dentistry at IISc,
Bangalore.

The technology for depositing crystalline hydroxyapatite (HA) coating on metallic

implants using plasma spraying has been established by CSIR for metallic implants
for orthopaedic and dental applications. CSIR-CGCRI’s coating technology has gone
through clinical trials and, technology transfer to interested industries is yet to take
place. CSIR- CGCRI has also developed a simple and economical wet chemical
synthesis process to make calcium phosphate (CaP)-based granules of different sizes
and porosities, for dental and bone filling applications (see Fig. 3.5). This process
provides high-purity HA and HA + TCP (biphasic) granules with high crystallinity
and good biological properties. Multi-ion-doped HA-based bioceramics, are being
developed at CSIR-CGCRI and IISc, Bangalore for accelerated tissue integration
with antimicrobial properties.
Bone cement is being used for fixing implants at the hip and knee joints. Using
a different bioceramic composition than CASPA, developed by SCTIMST scien-
tists, CSIR-CGCRI researchers formulated an injectable bone cement with patented
composition having the ability to release drugs in dental and bone defect filling
applications. An injectable biodegradable bone cement is being designed at CSIR-
CGCRI. The technology constitutes composition and preparation of self-setting,
injectable bone cement, with and without drugs. The process is inexpensive and

a
c

Fig. 3.5 (a) Calcium phosphate granules/scaffolds for dental and orthopaedic applications
(b) BioGraft packaging of final product of (a); (c) Hydroxyapatite-based orbital implants,
commercialised products developed, and clinically tested (Images courtesy CSIR-CGCRI)
3.3 Bones and Teeth 67

produces cement with excellent injectability, setting, and biological properties. Clin-
ical trials are completed and modification of the cement with radiopaque particles to
enable post-implantation identification and evaluation is in progress.
The Functional Materials Group at CSIR-NML, led by Arvind Sinha, is among
the pioneers in India to initiate research on biomimetic materials (that mimic biolog-
ical processes) using nanomineralisation processes, akin to matrix-mediated biomin-
eralisation. The group has developed and patented a number of processes for the
synthesis of nanosized hydroxyapatite and biphasic powders and nanocomposites
of various types: injectable, polymer-hydroxyapatite, polymer biphasic to carbon
fibre-reinforced polymer hydroxyapatite.
It is interesting to note, that even in the absence of any biological growth factor, the
nanopowders and nanocomposites developed by CSIR-NML exhibit bone healing
processes (osteoinduction and osteointegration). This was a collaborative work
between CSIR-NML and CSIR-CCMB, Hyderabad. Different polymer-bioceramic
nanocomposites developed by CSIR-NML exhibit mechanical properties (compres-
sive strength and modulus) close to those of cancellous bones (spongy bones found
at the ends of long bones, in the pelvis, ribs, skull, and the spinal column).

The technology of nanobioceramics has been transferred from CSIR-NML

to different industries, namely M/S Eucare Pharmaceuticals, Chennai; M/S
Surgiwear Pvt Ltd, Shajhanpur; and M/S IFGL Pvt Ltd, Kolkata. Three prod-
ucts, namely SYBOGRAF, SYBOGRAF PLUS, and SHAP are already in the
market.

In collaboration with an Indian industry, CSIR-NML is also involved in the devel-

opment of the third-generation ‘biodegradable metallic implants’. These materials
are being designed to support the injured part through the restorative process and are
anticipated to degrade within the body, thus avoiding the need for revision surgeries.
The mechanical strengths of the currently used biodegradable polymer implants are
very poor for use as orthopaedic implants. Therefore, metallic biodegradable alloys
(Mg-based, Fe-based, and Zn-based) are currently being developed at CSIR-NML
for orthopaedic applications.
In new research programs at CSIR-NML, Mg-based alloys are preferred, because
of their comparable elastic modulus (ratio of stress to strain) to that of human bone,
eliminating stress shielding and implant loosening issues. In addition, Mg alloys
are reported to stimulate the growth of osteocytes and are biocompatible. CSIR-
NML has developed a series of Mg-alloys through conventional melting and casting.
Although the requisite mechanical properties are achieved in Mg-alloys through post-
processing, the degradation rates of the alloys are much higher than those required for
biodegradable implants. Therefore, the present focus at CSIR-NML is on achieving
desired degradation rates through: (i) alloy design strategies; (ii) surface modification
of the developed alloys; (iii) development of suitable biocompatible coatings.
68 3 Scientists at Work in India

Balani’s research group at IIT Kanpur, focuses on hydroxyapatite (HA)-based

coatings and scaffolds. The group has used carbon nanotube (CNT) material to
significantly toughen HA, while attaining enhanced bioactivity. Further, his group
has adapted functionally gradient materials to provide surface bioactivity, while
engineering a tougher material for biological applications.
Dhara’s group at IIT Kharagpur has developed a green machining approach, as
a net-shape forming technique, for fabricating customised products, like ceramic
crowns, Ti6Al4V-based dental roots, hybrid mandible/bone plates, etc.

Extensive commercialisation efforts are currently underway through Dhara’s

own start-up company, Amnivor Medicare Pvt. Ltd, which is focused on devel-
opment of value-added products for skin, bone, and healing of osteochondral
defects (injury to the smooth surface on the end of bones).

The products of Amnivor include wound dressings, hemostats, dental solutions,

and various biotechnology products like bioink for 3D printing and 3D cell culture
matrices.
Although HA-based porous scaffolds are under development in the last three
decades, the naturally derived biomimetic HA, with tunable elastic modulus and
strength, together with faster biomineralisation property, remains to be achieved.
To address this specific issue, a group of researchers led by Saumen Mandal from
NIT Surathkal collaborated with IISc researchers to develop a scalable biomimetic
synthesis approach, to obtain submicron HA powders, from marine benthos (Fig. 3.6).
Depending on pore-formers, the scaffolds (with a range of porosity up to 51%, with a
larger range of pore sizes of up to 70 μm) were fabricated. A combination of moderate
compressive strength (12–15 MPa) with an elastic modulus of up to 1.6 GPa was

Fig. 3.6 Development of biomaterials from marine benthos (Collaboration between Mandal’s group
at NIT Surathkal and the author’s group at Indian Institute of Science, Bangalore)
3.3 Bones and Teeth 69

obtained with HA, derived from cuttlefish bone, and with wheat flour as the pore-
former. Most importantly, this specific HA scaffold supports faster nucleation and
growth of the biomineralised apatite layer with full coverage, within three days of
incubation in simulated body fluid, as well as better osteoblast cell proliferation,
in comparison with those of the synthetic counterpart. The technology of adherent
HA/ZrO2 coatings on metallic substrates, such as titanium alloy and stainless steels,
is established at low processing temperatures.

3.4 Cartilage, Bone, Cardiac, and Skin Tissue Engineering

In this subsection, I review advancements in Indian laboratories on translational

approaches to replace damaged tissues or whole organs and directions for further
development. The research activities of the Biomaterials and Tissue Engineering
group of Kaushik Chatterjee at IISc Bangalore can be broadly divided into the
following three areas. Firstly, this group has developed 3D scaffolds from novel
biodegradable polymers and polymer nanocomposites, incorporating different types
of ceramic and carbonaceous nanomaterials to promote tissue generation in the scaf-
folds. Scaffolds are prepared by various techniques such as 3D printing, porogen
leaching, and electrospinning. Secondly, engineering of organotypic tissue models
is ongoing.

The most recent research in Chatterjee’s group involves studying human cells
in 3D scaffolds towards engineering tissues in vitro, that mimic the cell
response in vivo to facilitate the study of cell biology and drug screening
in tissue-like environments, including breast tumour, intestinal, and cardiac
tissues.

Thirdly, Chatterjee’s group is working on additive manufacturing of Ti-alloys and

surface engineering techniques for use in the next generation of orthopaedic implants
with enhanced mechanical and biological performances.
The research contributions of Dhara’s group at IIT Kharagpur are based on
a fundamental understanding of materials property in relation to manufacturing
processes, customised implant development, cell–material interactions, and in vivo
biocompatibility. His research has been translated to deployable technologies and
commercially viable products through indigenously developed platform technolo-
gies. The three focus areas of his group are engineered biomaterials for cost-effective
therapeutics towards skin and skeletal tissue regeneration; customised dense, and
porous titanium/ceramic implants through novel powder metallurgy-based tech-
niques, such as coagulation casting and plastic dough processing; and simple green
approaches for the preparation of antimicrobial, biodegradable radiopaque polymers,
and functionalised carbon dots for healthcare applications.
70 3 Scientists at Work in India

In the domain of engineered biomaterials, Dhara’s group has utilized several

approaches to reprocess biowaste (fish scale, egg shell, sea shell, placenta, and onion
peel) for skin and skeletal tissue regeneration. Dhara has also formulated several
bioengineered products based on the combination of Collagen I, Collagen II, and
decellularised extracellular matrix. He developed a chitosan citrate gel for osteo-
chondral defect healing. Further, carbon quantum dots-doped calcium phosphate
nanorods was demonstrated to facilitate ectopic chondrogenesis via activation of the
HIF-α/SOX-9 pathway.
The tissue engineering group at PSG Institute of Advanced Studies, Coimbatore,
has been working on scaffolds for damaged human knee meniscus replacement,
and to develop techniques that enhance the growth of primary human meniscus
cells. The challenge in meniscal tissue engineering is the lack of homogeneity in
the meniscus—be it from difference in cell types, collagen arrangements, biphasic
behaviour, or geometrical differences. To address such a challenge, the researchers
of PSG Institute developed poly-ε-caprolactone/carbon nanofiller scaffolds with
high electrical conductivity and moderate roughness which exhibit enhanced cell
attachment and proliferation in simulated body fluid and phosphate buffer saline.
Poly-ε-caprolactone-based nanocomposite scaffolds with different concentrations of
carbon nanofillers (carbon nanofibres, nanographite, and exfoliated graphite) have
been studied to investigate the influence of electrical conductivity and biomolecule
supplementation for enhanced human meniscal cell attachment, and proliferation.
Nanoporous honeycomb garland-like structures are created on the pore walls of
these scaffolds. Through biochemical and immunohistochemistry analysis of these
scaffolds, in a rabbit model, biocompatibility has been established, in collaboration
with PSG Institute of Medical Sciences and Research and the Ortho One Hospi-
tals Group, Coimbatore. Another collaboration is in place with Innov4Sight Health
and Biomedical Systems Private Limited, a Bangalore-based company for stem cell
research.

While working on bone and neural tissue engineering, PSG Institute of

Advanced Studies, Coimbatore, has set up research collaborations with RMIT
University and St. Vincent Hospital, Australia, to develop nerve guidance
conduits.

A research group at the Central Leather Research Institute (CSIR-CLRI)

has developed a novel graphene-metal-amine-reinforced haemostatic and wound
dressing biomaterial. The biomaterial has synergistic effects on blood clotting and
has antibacterial, wound healing, and absorptive properties. The biomaterial has more
fluid absorption capacity and higher mechanical strength than those of conventional
dressings.
Neetu Singh’s laboratory at IIT Delhi has developed a plasma-induced graft
polymerisation method to improve the cell adhesion property of Bombyx mori silk
fibroin films (SF), which enables the development of silk-based surface coatings
3.4 Cartilage, Bone, Cardiac and Skin Tissue Engineering 71

with enhanced cell adhesion profile as well as spatial control over cell adhesion.
Further, the group has demonstrated that stem cells can be differentiated into bone
and cartilage cells on the same scaffold without adding any exogenous enhancers.
The control over the release kinetics in the range of a few hours to an extended
period of time (temporal control), for simultaneous delivery of signaling molecules
has also been achieved. A region-specific activity of biomolecules, by patterning the
silk substrates to direct cell adhesion using nanoparticles, has also been investigated.
For bone tissue engineering applications, the scaffold has been modified to improve
antimicrobial properties to combat biofilm formation of antibiotic resistant bacteria,
without compromising its biocompatibility and stem cell differentiation potential.

A 3D scaffold system developed at IIT Delhi, supporting fast and efficient

differentiation of stem cells into osteoblasts and chondrocytes, advanced the
field of tissue engineering towards creating the complex architecture of a tissue
from stem cells, which has been a long-standing problem.

Naresh Bhatnagar’s research group at IIT Delhi has developed manufacturing

protocols for the fabrication of a commercially competent vascular stent, using
PLA/PCL blends. From optimisation of material processing and manufacturing
processes to surface properties evaluation and limited cytocompatibility assess-
ment—the research delves into an end-to-end study of immense translational value.
An innovative technology was developed allowing for the fabrication of dimen-
sionally accurate stent tubes in a single step process. Surface properties have been
improved to induce better cell-substrate interaction.
At IIT Bombay, a number of research groups led by faculty members, including
Jayesh Bellare, B. Ravi, Rinti Banerjee and Rohit Srivastava a.o. have contributed
significantly to the field of biomaterials and implants. Bellare’s work has led to the
invention of biodegradable bone graft materials.
Rinti Banerjee’s group works on smart, stimuli-responsive biomaterials for drug
delivery, point of care diagnostics, medical devices, and technologies for global
health. The work in Banerjee’s group encompasses the entire spectrum from bioma-
terial development to in vivo evaluation and translation for scale up and commer-
cialisation, working closely with clinical and industry partners. Banerjee’s group
has developed many commercially viable technologies, seven of which have been
licensed to industry partners. This includes smart in situ gels for depot intravesical
drug delivery in the urinary bladder. This patented Urigel technology focuses on elim-
inating the barriers to delivery of drugs through the bladder wall while preventing
washout by urination.

The Urigel technology and its application for chemotherapeutic and

immunotherapy in bladder cancer, have been licensed to Ferring Pharmaceu-
ticals.
72 3 Scientists at Work in India

3.5 Eyes, Nerves, and Ears

About 40–50% patients are single-eyed, amongst 60–70 lakhs of blind people in
India. Significant demand for functional and cosmetic rehabilitation for ailing,
single-eyed patients persists in India. A unique product developed by CSIR-CGCRI
scientists is the orbital implant for eye surgery.

New design concepts of integrated orbital implants were conceived and manu-
facturing technology was developed to produce highly porous, yet strong orbital
implants, using bioactive hydroxyapatite by CSIR-CGCRI scientists.

The implant comes in different sizes, to suit different patients (see Fig. 3.5). Its
high porosity enables tissue ingrowth, providing the natural eye environment that is
synchronised with the other natural eye. Clinical trials are complete and technology
transfer to interested industries is being pursued.
In the field of peripheral nerve regeneration, the studies at Debrupa Lahiri’s group
at IIT Roorkee are focused on improving cell adhesion and providing electrical guid-
ance for axonal regeneration. Her group is currently exploring a different, second
phase of reinforced polymeric matrices. For skin regeneration, this group has devel-
oped a fully biodegradable scaffold, with desired physical and mechanical properties.
It has been used in the rapid healing of deep acute and chronic wounds. The scaffold
demonstrates the capability to heal severe burn wounds, to prevent bacterial infec-
tion, to reduce inflammation, and to regenerate burnt tissues. The researchers at IIT
Kanpur (Ashok Kumar’s group) have been working on the repair and regeneration of
damaged nerve tissues. With strategies for bone regeneration and nerve guidance in
place, Kumar’s group is undertaking the challenging problem of vertebral disc and
spinal cord injuries.
Limited efforts have been invested in India to improve the performance of cochlear
implants in the domain of ENT surgery.

IIT Guwahati researchers, led by S. Kanagaraj together with IISc researchers

and ENT surgeons of North Eastern Indira Gandhi Regional Institute of
Health and Medical Sciences, Shillong, have been conducting interdisciplinary
research to improve the performance of conventional cochlear implants.

The team is working on a cerium-based electrode material, that can scavenge

excess reactive oxygen molecules in order to preserve residual hearing after cochlear
implant fixation. Most commonly used CI electrodes have the outer insulating layer
made up of silicones. Some studies have shown that the silicone layer can be used
as a drug delivery medium in the location of the CI. In their unpublished research,
Kanagaraj’s group investigated the pathways to control the ROS by local antioxidant
3.5 Eyes, Nerves, and Ears 73

delivery to preserve the residual hair cells, particularly by coating the electrode of
the CI with nanoceria or silicone-nanoceria composite. This is important as medium
to long-term local delivery of antioxidants remains a challenge.
Nanoceria, an antioxidant material having high oxygen storage capacity and
unique redox property of changing the oxidation state between Ce3+ and Ce4+ , based
on the environmental conditions, was used as a catalyst and radical scavenger. The
use of nanoceria can potentially reduce the oxidative damage of sensory hair cells.
In this research program, the cytocompatibility of the coated electrodes was inves-
tigated using hair cell/neuronal cell lines and also primary hair cells isolated from
murine organ of Corti. After finalising suitable composite properties and concentra-
tion/dosage, the biocompatibility of nanoceria-coated CI electrode and the silicone-
nanoceria composite-insulated CI are currently being investigated in murine models,
with a particular focus on evaluating the systemic and local inflammation and hair
cell damage in the implanted animals.

3.6 Antibacterial Biomaterials to Combat

Implant-Associated Infections

Infection is one of the major reasons, which causes implant failure. Globally, implant
failure from infections stands at about 2–7%, over the implant’s lifetime. The
gram-positive bacteria, Staphylococcus aureus, has been found to be extensively
involved in implant-related infections. More than 30% of failures or rejection of
orthopaedic implants are directly linked to post-surgical infection. Aseptic loosening
and periprosthetic bacterial infection (around an implant) are the prime causes. The
existing remedy lies with antibiotics, but high doses cause unnecessary whole-body
exposure and associated problems, namely antibiotic-resistance. To avoid this effi-
ciently, on-site delivery of antibiotics, post-surgery, is required. It is challenging
to modify metallic implants to release drug for a few weeks, without affecting their
structural, mechanical, and biological attributes. At present, no such metallic implants
are commercially available.
To address this problem, the research group of Debrupa Lahiri and Swati Haldar
at IIT Roorkee is also designing systems for sustained drug release for currently used
orthopaedic implants. The group has been avidly engaged in exploring biodegradable,
physiology-friendly alloys, and composites with mechanical properties, similar to
that of human bone, to circumvent revision surgeries, stress shielding, and bone weak-
ening issues. Also, magnesium–zinc (Mg-Zn) alloys and composites, in combination
with hydroxyapatite (HA), are being investigated with encouraging results. Since
magnesium has a high corrosion rate under physiological conditions, the group’s
research at IIT Roorkee focusses on its corrosion resistance, while improving its
mechanical integrity.
The need for more efficient drug delivery strategies are leading to more research
on sophisticated drug-releasing implants, as outstanding alternatives to conventional
74 3 Scientists at Work in India

clinical therapies. Recent clinical trials have demonstrated that this technology can
improve both quality of life and life expectancy of patients. Further, the surface needs
to be optimised to make the drug-releasing period longer.

At IIT Roorkee, Lahiri’s research group has designed HA-coated metallic

orthopaedic implants, with the surface being modified to release drug,
post-implantation, for around three weeks.

In addition, they are also exploring a drug-releasing matrix to reduce friction, as

well as, the wear and tear of implants at the joints.
Balani’s group at IIT Kanpur has also assessed the adhesion strength of S. aureus
gram-positive bacteria on various biosurfaces (such as polymeric ‘ultra-high molec-
ular weight polyethylene (UHMWPE)’, ceramic ‘HA’, and metallic ‘stainless steel
and Ti-6Al-4V’ real-life bone-implant substrates). They have utilised molecular
dynamic simulation to visualise adhesion events on these biosurfaces and quanti-
fied the invariant long-range forces, that combine with short-range forces to allow
surface proteins of bacteria to interact.

The protein-unfolding events, visualising detachment of bacteria (correlated

with experimental de-adhesion events), are being shown for the first time by
Balani’s research group at IIT Kanpur.

Balani’s recent work on constructing porous HA-based scaffolds, with antibacte-

rial and anti-oxidant efficacy (with ZnO and CeO2 addition, respectively), is aimed
towards attaining multifunctional capability for bone-scaffolds. The aspects of incor-
porating porosity at multi-length scales in HA-based matrix are being engineered
(nanoporosity for enhancing protein-material interaction at molecular length scale,
micro-texture for assisting directional-cell growth, and bulk-porosity for ensuring
vascularisation effects for expedited healing). Additionally, his work on polymeric-
liners for hip joints—where, his group has utilised Al2 O3 reinforcements and carbon
nanotubes to provide enhanced tribological resistance to UHMWPE—has gained
attention. The multi-length scale tribological aspects highlight how the ceramic
reinforcements show enhanced scratch resistance, whereas metallic reinforcement
provides enhanced fretting resistance.
A group of researchers at VIT Vellore explored the feasibility of RF plasma
treatment in providing the necessary sterility to the implant. They have studied the
effect of RF cold plasma on titanium and stainless steel surgical implants—Ti-6Al-
4V (Ti64) and 316L SS—to prevent bacterial adhesion. A stable antibacterial activity
was obtained in seven days post-plasma treatment.
3.6 Antibacterial Biomaterials to Combat … 75

Biomaterial approaches

Au nanoparticles (1.5-6 nm) mediated HA-Fe3O4 HA-10% ZnO

planktonic and biofilm growth inhibition (magnetic stimuli) (electrical stimuli)
Small 11 (2015) 3183-3193 Journal of the American Ceramic Society 96 (2013) 2100-2108
Biophysical stimulation

Anti-biofilm action of DC electric field

E-field mediated bacterial growth inactivation (ROS production and membrane depolarization)
Carbon 81 (2015) 193-202 J. Biomedical Materials Research: B 100 (2012) 1206–17

Fig. 3.7 Antimicrobial strategies to prevent implant-associated bacterial infection (summary of

author’s research at IIT Kanpur and at IISc, Bangalore)

At the author’s group at IISc, both biomaterial and biophysical antibacterial

approaches have been successfully used. In the context of antimicrobial bioma-
terials, ultrasmall gold nanoparticles (0.8–1.4 nm) and hydroxyapatite composites
reinforced with Fe3 O4 and ZnO were designed to mitigate MRSA infections. Further-
more, adjuvant treatment approaches, such as external biophysical stimulation in the
form of electric and magnetic fields, were demonstrated to enhance the bactericidal
properties of the developed antimicrobial biomaterials (Fig. 3.7).

Some of the important scientific discoveries from India in the Bioengi-

neering domain include the synergistic interaction between magnetoac-
tive/electroactive properties of biomaterials and magnetic/electric stimuli
(respectively) towards bacteriostatic/bactericidal properties, in vitro (author’s
research at IIT Kanpur and IISc, Bangalore).
76 3 Scientists at Work in India

3.7 Regenerative Engineering

The author’s research group at IISc, Bangalore, has investigated biophysical stimu-
lation of cell functionality on engineered biomaterials. The research focussed partic-
ularly on stem cell differentiation for cardiac and/or neurodegenerative diseases.
Their research has shown that electrical stimuli can inhibit cell proliferation,
while promoting early cell differentiation on a number of engineered biomaterials
(doped PANI, PVDF-CNT, HA-CaTiO3 , etc.) and in microfluidic devices under
dynamic culture conditions. His research team solved Poisson’s equation with appro-
priate boundary conditions to rationalise the role of bioelectric stresses on cellular
deformation and identified critical stimulation conditions for electroporation.

The author’s research group unraveled that the intermittent delivery of

magnetic field stimuli drives osteogenesis of human mesenchymal stem cells
on magnetoactive biomaterials.

This body of work has profound significance on the bioengineering strategies for
neural, bone, and cardiovascular regenerative applications.
Hardik Pandya’s group (Biomedical and Electronic Engineering Systems Labo-
ratory and Advanced Microsystems and Biomedical Devices Facility) at the Depart-
ment of Electronic Systems Engineering in IISc Bangalore works closely with a
team of clinicians from India and abroad, to develop systems and solutions tailored
to address unmet clinical needs. The key focus areas are label-free phenotyping of
cancer tissues, cytology-based point-of-care screening for cancer, development of
novel steerable catheters for atrial fibrillation and tracheal stenosis, platforms for
rapid on-chip antibiotic susceptibility testing, neurophysiological interventions to
evaluate mental wellness, development of the phenotypic brain atlas model, novel
futuristic bioresorbable sensors for the recording of biopotentials, etc. Each research
problem is addressed by an interdisciplinary team with constant feedback and inputs
from clinicians. The team leverages advances in microfabrication, electronic systems
engineering, additive manufacturing, and machine learning, while combining with
established techniques and protocols in biology and medicine to develop clinically
relevant solutions.
A number of researchers in the laboratory of Mohanty at AIIMS, New Delhi;
and Barui and Datta at IIEST, Shibpur are working towards developing an insightful
understanding of the functionality of different types of stem cells on tissue engineered
scaffolds.
Ashok Kumar’s research group at IIT Kanpur focuses on the development of the
new generation of cryogel biomaterials, smart polymeric materials, and nanomate-
rials towards bone tissue engineering applications. His research group has devel-
oped an indigenous cryogel technology, used for stem cell separations, tissue engi-
neering, and regenerative medicine, such as biomedical devices (for instance, an
extracorporeal bioartificial liver device).
3.7 Regenerative Engineering 77

In another direction, the research team of Ashok Kumar at IIT Kanpur has utilised
temperature-responsive smart polymeric material in self-assembling biomolecules
and cells for their enhanced utility in regenerative medicine. Further, the laboratory
focuses on natural and synthetic nanomaterials for their therapeutic applications in
different healthcare problems: cartilage, bone, skin, cardiac, liver, and neural tissue
engineering applications. In liver diseases, the focus of Kumar’s group is to explore
different treatment possibilities to bridge the gap between liver transplantation and
regeneration.

Ashok Kumar’s group at IIT Kanpur recently patented an integrated bioartificial

liver device, with the aim of up-scaling the design for pre-clinical trials in larger
animal models. The group is working towards exploiting the therapeutic aspects
of exosomes (nanosized vesicles that can travel between cells) in liver tissue
engineering.

Further, these materials are being explored for musculoskeletal defect healing and
bone regeneration. For example, pre-clinical trials on rat and rabbit in tibia and cranial
bone defect models have validated various therapies and approaches using developed
scaffolds and fillers based on cryogels, 3D printed scaffolds, and injectable bone
cements. Kumar’s group has successfully fabricated antioxidant polymeric materials
and developed them into 3D scaffolds, which have shown promising applications for
developing cardiac patches for treatment of myocardial infarction.
At the Ceramic Engineering Department in IIT (BHU), Varanasi, Dubey has estab-
lished a state-of-the-art biomaterials laboratory to establish research programs in the
broad area of ‘Piezoelectric Biomaterials’. In particular, his group is focusing on
developing an understanding of the combined action of electrostatic and dynamic
electrical stimulation on antibacterial and cellular responses of piezoelectric bioma-
terials, such as perovskite niobates, silicates, and titanates (see Fig. 3.8). Towards
developing a theoretical understanding of these processes, his research laboratory
is involved in computational analyses of the functional response of electromagnetic
equivalents of mammalian and bacterial cells.

Among the piezoelectric perovskites, Dubey’s research group demonstrated

the biocompatibility of sodium potassium niobate [Nax K1−x NbO3 (x = 0.2 −
0.8), doped with Li]-based functionally graded composites, using a series of
electro-mechanical, impedance spectroscopy, and in vitro cellular studies.

In addition to the inherent piezoelectric materials, Dubey’s research group at

IIT(BHU), Varanasi, induced ferroelectricity, which is similar to that of cortical
bone, even in non-piezoelectric hydroxyapatite, via the concept of development of
a functionally graded material with sodium potassium niobate. Here, a reasonable
78 3 Scientists at Work in India

Functionally graded materials Poling induced Crystallization

Electrospun scaffold for
for bone replacement
peripheral nerve regeneration

J. Cry. Growth, 382, 7, 2013.

(Embryonic neurons)

Chemical and Electrical

treatment induced Bioactivity

RSC Adv., 2014, 4, 24601 Ionics, 1351, 25, 2018

RSC Adv., 2015, 5, 19638
Bactericidal response on poled surfaces

J. App. Phys.,114, 124701 (2013)

PVDF- polyvinylidene difluoride

LNKN- Li-doped sodium potassium niobate
HA/ HAP- Hydroxyaptite

Fig. 3.8 Piezoelectric Biomaterials Research at IIT (BHU), Varanasi (Image courtesy Ashutosh
K. Dubey)

combination of bone-mimicking dielectric and electrical response such as, dielec-

tric constant (38), AC conductivity [~10–9 /(ohm cm)], piezoelectric strain coef-
ficient (d33 -4.2 pC/N), electromechanical coupling coefficient (0.17), mechanical
quality factor (81), and remnant polarisation (0.06 μC/cm2 ) has been achieved. His
group further developed PVDF-NKN-based electrospun scaffolds and investigated
the modulation of the neural cell functionality on those scaffolds. The pre-clinical
study on the in vitro-tested biomaterial systems has been planned.

3.8 3D (Bio) Printing of Biomaterials, Tissues, and Organs

In the field of additive manufacturing, laser or electron beam–based 3D printing

is widely investigated for biomedical applications. In a recent work, the author’s
research group at IISc Bangalore has developed a quantitative understanding of the
process physics of 3D binderjet printing, which allows processing at physiologically
relevant conditions (Fig. 3.9). This work proposed the formulation of an in situ poly-
merisable acrylic binder for printing implantable metallic biomaterials. The author’s
team has insightfully extended the Washburn model to rationalise the timescale of
binder infiltration to the powder bed with respect to polymerisation kinetics. Based
on this scientific study, his research group collaborated with a team of neurosurgeons
from Ramaiah Memorial Hospital, Bangalore to conduct a clinical study on the use of
3.8 3D (Bio) Printing of Biomaterials, Tissues, and Organs 79

Fig. 3.9 Schematic of the Salient Scientific Research on 3D Binderjet Printing (inkjet printing) of
Implantable Biomaterials at IISc, Bangalore

patient-specific cranioplasts to treat decompressive craniectomy in human subjects.

A pilot study is currently under progress in another hospital in India.

The technology of the clinically tested cranial prosthesis involves an integrated

methodology, comprising advanced image processing of patient’s CT scans, 3D
inkjet printing of patient-specific cranium models, and conventional fabrication
of acrylic bone flap and sterilisation.

The research group of Sourabh Ghosh at IIT Delhi is working in the interdis-
ciplinary areas of biomaterials science, developmental biology, and cell signaling.
The group has developed an in vitro model of mesenchymal condensation during
chondrogenic development. Mesenchymal condensation is a pre-requisite of chon-
drogenesis during embryonic development. The group is trying to understand how
subtle variation in morphology and stiffness of nanofibrous silk protein matrices
can induce aggregation of human mesenchymal stem cells, mimicking early stage
chondrogenesis.

In the field of 3D bioprinting, Ghosh’s research group at IIT Delhi developed

anatomically relevant, phenotypically stable cartilage constructs, using silk-
gelatin bioink.
80 3 Scientists at Work in India

These scaffolds exhibited close similarities in the signaling pathways with embry-
onic cartilage development, suggesting that the engineered cartilage tissue is a
prospective tissue equivalent with the potential of providing the essential instructive
elements for activating pathways of organogenesis.
Using 3D bioprinting, Ghosh’s group at IIT Delhi has tried to recapitulate in vivo
endochondral ossification-based limb skeletal development, specifically chondro-
genic condensation and hypertrophic cartilagenous template development. His group
identified the involvement of IHH signaling, indicative of the development of bony
collar by perichondral ossification. Ghosh’s research group also reported that silk
fibroin protein activates Wnt-signaling pathways to trigger chondrogenic differ-
entiation, as well as Hedgehog and parathyroid signaling pathways, to modulate
osteogenic differentiation of progenitor cells. The group has further extended this
insight to develop an in vitro organoid model of the dermal papilla of the human hair
follicle and a human skin equivalent.
Researchers under the guidance of Subha Narayan Rath and Falguni Pati at IIT
Hyderabad have developed a novel 3D-printed polymer bioactive glass composite for
patient-specific bone defect reconstruction. The biomaterial is currently at the stage
of animal testing to study new bone formation, osteoinductive ability, and blood
vessel infiltration. Rath used 3D bioprinting methods to fabricate blood vessels,
bone, and cartilage. To achieve this, mesenchymal stem cells (MSCs) are isolated
from primary sources, like adipose tissue and umbilical cord and used in a number
of bio-inks by 3D bioprinting methods. De-cellularisation tissue-derived bioink is
promising to lead a new generation of bioinks for tissue-specific induction, wherein
Pati’s group is associated for fabrication of the tissues.

Pati’s group, along with a team of researchers from the Asian Institute of
Gastroenterology (AIG, Hyderabad), is currently working on developing a
macro-encapsulation device for allogenic islet cell transplantation for diabetic
patients. In addition, his group uses microfluidic chips to test MSC differen-
tiation, cancer stem cell growth, and subsequent drug testing in lab-on-chip
devices.

Silk fibroin (SF)-polyvinyl alcohol (PVA)-blended electrospun nanofibrous scaf-

folds have been developed to investigate the attachment and proliferation of primary
human meniscal cells at PSG Institute of Advanced Studies, Coimbatore. A blend
of silk: PVA at 3:1 ratio is suitable for meniscus cell proliferation, when compared
to pure SF-PVA nanofibres. Improved compressive and dynamic mechanical prop-
erties, similar to those of the native human meniscus, were measured. The in vivo
biocompatibility study confirmed that the scaffolds were able to induce angiogenesis
with minimal inflammatory response. Future translational research being planned at
PSG Institute of Advanced Studies include a large animal trial in a pig model for
3D bioprinted scaffolds, and meniscus reconstruction in vitro studies in a designed
bioreactor.
3.8 3D (Bio) Printing of Biomaterials, Tissues, and Organs 81

Biman Mandal’s group at IIT Guwahati have employed conventional and

latest 3D bioprinting techniques to intricately mimic the architecture of
organs/tissues to understand the underlying cell-material crosstalk and its role
in tissue regeneration.

Mandal’s laboratory specifically focuses on recreating functional tissues, organs,

and implants using naturally derived biodegradable biomaterials, i.e. Indian endemic
silk in combination with stem cells. Mandal’s group has developed a number of
prototypes, which are in various phases of pre-clinical/clinical validation. These
include smart wound dressings for diabetic foot ulcers, skin grafts for burn injuries,
vascular grafts for bypass surgery, vascularised bone grafts as orthopaedic implants,
a beating cardiac patch for myocardial infarction, a bioartificial pancreas releasing
insulin for type-1 diabetes, 3D-printed intervertebral disc and knee meniscus as
orthopaedic grafts and minimally invasive anti-cancer drug-eluting injectable gels
for cancer treatment. Similarly, the group has developed multiple in vitro human
disease models, which can contribute to industry in high throughput drug screening
and drug development.

3.9 National Institutes of Importance and Centres

of Excellence

3.9.1 Sree Chitra Tirunal Institute for Medical Sciences

and Technology, Thiruvananthapuram

The Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) is
an institute of national importance under the Department of Science and Technology,
Government of India. In the last few decades, several medical device technologies
developed here have been transferred to industrial partners for manufacture and
commercialisation—including the Chitra heart valve, a process for preparation of
extracellular matrix scaffolds from mammalian cholecyst/jejunum/urinary bladder,
a rapid urinary tract infection diagnostic kit with antibiotic sensitivity test, a fibrin
sealant, a vein viewer, and warmers of IV/blood fluid (see Fig. 3.10).
A team of biomaterials researchers at SCTIMST has developed a new-generation
bioactive bone cement, named CASPA. This is a self-setting formulation, containing
osteoconductive inorganic phases, that leads to faster healing of bone defects. Bioac-
tive injectable cements are now highly sought-after materials in specialties like
orthopaedics, maxillofacial, and spinal specialties, because of the potential advan-
tages of minimally invasive surgery and drug delivery, which can be applied for bone
repair and treatment, for example.
82 3 Scientists at Work in India

MulƟfuncƟonal Bio-acƟve bone cement 3D bioink formulaƟon Bio-ceramic coaƟng for

oligomers for dental
dental implants
applicaƟons • Bioac ve bone cement based • Gela n and liver cell-based
• Bio-ceramic materials were
• fast in situ step growth on novel inorganic-organic bioink formula on for
coated onto the surface of
photopolymeriza on for hybrid resins prin ng liver construct
tanium implants through
medical applica on • Composite exhibited good • Bioprinted construct showed
pulsed laser deposi on (PLD)
• the composite showed good mechanical proper es with that cells were func onal
• Excellent uniformity and micro-
physico-mechanical low polymeriza on and viable over a period of
structure were obtained under
proper es and shrinkage, enhanced 14 days (liver func on tests
op mized condi ons
polymerisa on shrinkage bioac vity, radiopacity and were carried out, namely
• In vitro cell compa bility
values biocompa bility albumin and urea synthesis
studies showed osteosarcoma
• op mized formula ons were • Excellent bonding of tooth tests)
cell adhesion and prolifera on
radiopaque, with bioac vity, structure with composite • Bioac ve coa ng showed
biocompa bility and no without the use of a bonding effec ve osseointegra on
cytotoxicity. agent

Drug-eluƟng bioacƟve FuncƟonalised chitosan Self-assembling polymeric

calcium sulfate cement composite membranes for dendriƟc pepƟdes for
guided dental Ɵssue regeneraƟon of periodonƟum
• The aim is to prevent the onset of bone
infec on during the period of me
regeneraƟon
• Guanidine-appended polydiacetylene (G-
prior to the material integra ng with • A novel membrane was made using PDA) was synthesized in the form of a self-
the host site quartnerised chitosan composi ng assembling nano-structured matrix for
• An bio c-elu ng calcium sulfate with stron um-doped apa te par cles poten al use as an ECM-mime c scaffold in
cement was shown to release • The membranes were found to be the regenera on of periodon a
gentamicin and vancomycin, reaching ideal for guided ssue regenera on, • The material was highly cytocompa ble
the minimum inhibitory concentra ons where a membrane is needed to with primary human periodontal ligament
in 17 and 47 days, respec vely isolate the wound from epithelial cells cells and supported the osteogenic
where ssue is lost due to periodontal differen a on of the cells upon induc on
disease

Fig. 3.10 Selected Technologies from Sree Chitra Tirunal Institute for Medical Sciences and
Technology

The essential validation of CASPA, as per the regulatory requirements, is

complete—including pre-clinical studies, while human clinical trials are under
progress.

Commercialisation efforts are effectively guided by TIMed, a Technology Busi-

ness Incubator for Medical Devices and Biomaterials at SCTIMST. In 2017–2018,
TIMed supported seven resident and two virtual incubatees in the healthcare domain
and was selected for the NIDHI Seed Funding Scheme of DST. This has enabled
TIMed to provide seed funds to its incubatees. The group launched the Social Inno-
vation Immersion Programme in the areas of ageing and health with BIRAC support,
and four TIMed Innovation Fellows were selected for the scheme.
According to the Institute’s Vision 2030: Perspective Plan, a 350-crore project
is envisaged for developing biomedical devices, particularly those related to arti-
ficial organ development and bioink, orthotics, robotics, and in vitro diagnostic
devices. SCTIMST aims to develop and transfer 40 innovative medical technolo-
gies to industry and take another 20 to advanced stages of development by 2030.
Medspark, a medical devices park, is planned to be set up on the premises of the
Bio 360 Life Science Park, being developed by the Kerala State Industrial Devel-
opment Corporation at Thonnakal in Thiruvananthapuram. It is a 180-crore project,
funded with financial assistance from the Government of India. The aim of the Park
is to create an environment for research and development in the area of medical
3.9 National Institutes of Importance and Centres of Excellence 83

devices and biomaterials, including testing and evaluation, manufacturing support,

technology innovation, and knowledge dissemination.

3.9.2 School of International Biodesign, All India Institute

of Medical Sciences, New Delhi

The School of International Biodesign (SIB) was built on the success of the Stanford
India Biodesign Program. SIB is implemented by DBT, at All India Institute of
Medical Sciences (AIIMS), New Delhi and IIT Delhi, in collaboration with QUT
Australia and Hiroshima University, Japan. Since the inception of the program, DBT
engaged the Biotechnology Consortium of India Limited (BCIL) to manage the
techno-legal activities of this program. The aim of this programme is to train the next
generation of medical technology innovators in India. This includes idea generation
through clinical immersion, need finding, need filtration at AIIMS, and prototype
development at IIT, along with IP generation, with the help of BCIL.
More than 50 prototypes have been developed so far, which have been further
refined, validated internationally, and tested in preclinical and clinical trials. This has
led to the development of over 30 medical devices, which were possible due to the
efforts of young innovators, i.e. 60 fellows and over 52 interns. Fifteen technologies
have been transferred, and 12 medical technology start-ups have been set up by the
fellows trained under this programme in sync with the ‘Start-Up’ India Program.
After completing the programme, many SIB fellows continued their profession in
the medtech field, with 38% in medtech industry and around 44% in start-ups.

3.9.3 Biomedical Engineering and Technology Incubation

Centre (BETiC), IIT Bombay

Based at IIT Bombay, BETiC is an inter-disciplinary multi-institutional initiative for

medical device innovation, headed by B. Ravi. Established in 2014, with support
from the government of Maharashtra; it comprises a network of 14 engineering and
medical institutes across the state.

The BETiC team has developed 50 medical devices as of 2019, and licensed
16 of them to start-up companies or industry for mass production.

BETiC started functioning from the OrthoCAD laboratory in IIT Bombay in early
2015, followed by two satellite centres at Visvesvaraya National Institute of Tech-
nology, Nagpur, and College of Engineering, Pune. The centre organises a Medical
84 3 Scientists at Work in India

Device Hackathon (MEDHA) in July and a week-long Medical Device Innovation

Camp (MEDIC) in September.
The CAD-CAM centre at Visvesvaraya National Institute of Technology (VNIT)
Nagpur is home to innovations, under the leadership of A. M. Kuthe. The group
has worked on fabrication of customised metallic implants and customised scaffold
fabrication using a bioplotter for bone tissue regeneration, whose biocompatibility
has been established using animal tests. Until now, around 11 clinical studies are
successfully completed, with implants and scaffolds fabricated at the CAD-CAM
centre, in diverse areas such as ridge augmentation, sinus lift, socket preservation
and guided bone regeneration. Kuthe’s group has also developed a non-invasive and
anesthesia-free medical device for diagnosis of glaucoma. It is a device to measure
intraocular pressure (IOP) through the eyelid. The main advantage offered by this
method is an increase in patient’s comfort and prevention of corneal infection. The
group has conducted many clinical studies with clinicians from Datta Meghe Institute
of Medical Sciences, Wardha.

3.9.4 Multi-institutional National Research Programs

IISc, Bangalore, is currently leading the Translational Centre on Biomaterials for

Orthopaedic and Dental Applications. The vision is to conduct innovative research
that will lead to biomaterials-based solutions in orthopaedics and dentistry. The
mission of this centre is to pursue transformative research that will usher in biomed-
ical device development through collaborative efforts of academia, and national
laboratories with intensive interactive inputs from clinicians and industries. With
the involvement of 43 researchers from multiple disciplines (including bioceramics,
biopolymers, biomechanics, mechanical engineering, dentistry, orthopaedic surgery,
and histopathology), and 27 young researchers, this centre is currently the largest
biomaterials-centric centre of excellence in India. The participants are from CSIR-
CGCRI, Kolkata; CIPET, Chennai; IIT Kanpur, NIT Rourkela, SCTIMST, Thiru-
vananthapuram; IIEST Shibpur; and Ramaiah University of Applied Sciences,
Bangalore (Fig. 3.11).
DBT has funded bioengineering and biodesign initiatives at IISc, Bangalore, in
two phases. This programme is currently at the Phase II stage. The broad objec-
tive of the programme is to strengthen the interdisciplinary basic and translational
research programs, by deep engagement with biologists and clinicians from clin-
ical research institutions, including Christian Medical College (Vellore), Mazumder-
Shaw Centre for Translational Research (Bangalore), St. John’s Medical College and
Research Foundation (Bangalore), National Institute of Mental Health and Neuro-
sciences (Bangalore), and a few hospitals in Bangalore. Other objectives include
training of MD degree holders to be biodesign innovators and continuing to foster
the bioengineering PhD program, by providing research facilities as well as academic
monitoring.
3.9 National Institutes of Importance and Centres of Excellence 85

Overview Centre Consortium

Vision: Innovative biomaterials-based solutions in Orthopedics and Dentistry
Mission: Transformative research leading to biomedical device prototype
development through collaborative efforts of Academia and National laboratories with
intensive-interactive inputs from Clinicians.

Clinical needs: In India, around 214 million patients suffer from orthopedic and dental
related diseases. Concerning the dental field, 11-37% edentulism occurs in (65-75) age
group. The Indian orthopedic and prosthetic device market is valued at $660 million

Impact: This Center of Excellence (CoE) has emerged as an important hub of

significant translational research activities to promote biomaterials- centric healthcare
research programs in other institutes (IIT Roorkee, IIT Guwahati, NIT Surathkal, VNIT
Nagpur, NIT Durgapur). CoE has involved more clinicians and MSMEs, to establish a
unique ecosystem to explore business opportunities in biomaterials and implants.

Pre-clinically validated Biomaterial implant prototypes

Ceramic femoral head Polymer-ceramic acetabular liner Metallic Dental Implant

Fig. 3.11 Overview of the Translational research activities of a national center of excellence on
Biomaterials for Orthopaedic and Dental Applications, currently being coordinated by the author
at IISc, Bangalore

3.9.5 Multi-institutional International Translational

Research Programs

Here, I present brief details of some of the recently concluded and ongoing multidis-
ciplinary translational research programs, wherein the author has taken the lead role.
The Indo–US Public–Private Networked R&D Centre on Biomaterials for Healthcare
involved 25 Indian and US young researchers (http://www.iitk.ac.in/indo_us_biom
aterials/). The author’s research group, then at IIT Kanpur and Brown University, led
this bilateral programme during 2008–2011. The outcome led to the development of
biomaterials for orthopaedics, corneal, dermal, cartilage, and cardiovascular tissue
engineering applications. Notable achievements of this centre were: (a) genotoxicity
of nanobioceramic composites; (b) HA-based electroconductive piezobiocompos-
ites; (c) development of polymer-based scaffold materials for cartilage tissue engi-
neering application; (d) injection molding of polymer-ceramic hybrid biocomposites;
and (e) investigating a CAD/CAM-based manufacturing route as well as 3D printing
route to fabricate complex-shaped implant materials.
Clinically, osteoporosis is one of the most common health risks faced by the
vast majority of ageing populations across the world, especially post-menopausal
women. The occurrence of this systemic skeletal disease eventually makes the bone
weak, porous, and fragile. The survival of implants in such patients is very low, as
osteoporosis affects the process of osseointegration, and patients otherwise have to
undergo revision surgery. This unmet clinical need has driven another international
86 3 Scientists at Work in India

Fig. 3.12 Some key results obtained in the Indo-UK Center on Glass-Ceramics for Osteoporosis
(a) Research Highlights (b) Micro-computed Tomography Analysis: Bone volume (BV) to total
volume (TV) ratio for glass-ceramic implant (LG26Sr) (4.5SiO2 -3Al2 O3 -1.5P2 O5 -3SrO-2SrF2 )
and commercial implant (HA-bioglass; HABG), in rabbit femur for different time periods. (*/#):
Significant difference (statistical) in terms of BV/TV ratio in case of HA-bioglass implant with
respect to 4 weeks implantation data at p < 0.05. The data are represented as mean ± SE
(Sabareeswaran et al. 2013)

program, the Indo-UK Biomaterials centre on glass ceramics for osteoporosis, at IIT
Kanpur (http://www.iitk.ac.in/UKIERI_biomaterials). The collaborating institutes
were SCTIMST, India, and three UK Universities (Birmingham, Warwick, and Kent).
Altogether, six co-PIs and 15 researchers have taken part in this interdisciplinary
research consortium. The implantation experiments with Sr-doped glass ceramics in
a rabbit animal model confirmed neobone formation, qualitatively using histolog-
ical analysis and quantitatively using micro-computed tomography (Fig. 3.12). The
osteoconductive property is comparable to that of a commercially available bioac-
tive implant (HA-based bioglass). This project has led to the development of novel
glass-ceramic implants that have been found to be biocompatible in vivo, with regard
to local effects after implantation, besides training a number of young researchers
from India and the UK.

3.10 Nota Bene

Several research groups at IISc Bangalore, IIT Kanpur, IIT Guwahati, IIT Kharagpur,
IIT Bombay, VNIT Nagpur, NIT Rourkela, IIT Delhi, SCTIMST, CSIR-CGCRI,
CSIR-NML, CSIR-CLRI, IIT Kharagpur, PSGIAS, IIT Roorkee, IIT (BHU)
Varanasi, IIEST Shibpur, CIPET Chennai, IIT Hyderabad, and SIB (AIIMS) have
been actively working on biomedical implants for orthopaedic, dental restoration,
cardiovascular, ophthalmic, ENT, cartilage and neurological applications, tissue and
regenerative engineering, and 3D bioprinting of biomaterials, tissues, and organs.
This has led to two unique centres of excellence—BETiC lead by Prof. B. Ravi at
IIT Bombay and the other is at IISc, Bangalore, sponsored by the DBT. BETiC, (a
3.10 Nota Bene 87

consortium of IIT Bombay, Tata Memorial Centre and VNIT Nagpur), is one of the
success stories. Recently, IIT Kanpur has initiated a centre of excellence in collabo-
ration with King George’s Medical University, Lucknow. Several micro, small, and
medium-scale enterprises (MSMEs) are now working to indigenise various medical
implants and devices that have been developed over the last several years.
A number of challenges, however, restrict more intense translational research
when taking laboratory-scale research to market. These challenges are presented in
Chap. 5 of this monograph. Many of these challenges are significantly addressed
in North America, Europe, and Australia. These facilitated significant translational
research in these continents, as discussed in Chap. 4 of this monograph.

3.11 A Path Ahead

The last three decades have shown that there is tremendous zeal and zest in the
community of biomaterials scientists to develop a new generation of biomaterials,
medical devices and implants, while providing newer insights into the science of
biocompatibility. I hope that key changes, that are suggested in this monograph,
will usher in an era of new and significant achievements, building upon the knowl-
edge base, enthusiasm, and hard work of the scientists, clinicians, entrepreneurs,
administrators, and science and technology facilitators of India.
Chapter 4
International Status

Abstract The quantum of translational research in developed countries is generally

high, with a better research ecosystem, having hospitals attached to many research
centres. As we have seen in the previous chapter, high quality research is ongoing
in academia and national labs, in India. However, the ecosystem in India is not yet
sufficiently developed to allow a streamlined and efficient approach to product devel-
opment and translation. In many developed nations, there are well-developed regula-
tory frameworks in place, better connectivity between biomedical manufacturers and
private companies, more corporate funding for research, and well-developed contract
research organisations. This chapter is intended to highlight the translational research
activities, which are key examples of successful research ecosystems. The examples
shown in the geographical map are no way meant to be an exhaustive list, but repre-
sent the work of major multi-institutional research centres around the globe. An
overview of the work of major research groups is summarised in Appendix C.

Disclaimer: The presentation of material and details in maps used in this chapter does not imply
the expression of any opinion whatsoever on the part of the Publisher or Author concerning the
legal status of any country, area or territory or of its authorities, or concerning the delimitation of its
borders. The depiction and use of boundaries, geographic names and related data shown on maps
and included in lists, tables, documents, and databases in this chapter are not warranted to be error
free nor do they necessarily imply official endorsement or acceptance by the Publisher or Author.

© Springer Nature Singapore Pte Ltd. 2020 89

B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0_4
90 4 International Status
4.1 Global Landscape of Biomaterials Research Consortia 91

4.1 Global Landscape of Biomaterials Research Consortia

4.1.1 Prometheus Group, at Katholieke Universiteit Leuven,

Belgium

The Prometheus Group of Katholieke Universiteit Leuven, Belgium, is a translational

platform in the field of regenerative medicine.

This is one of the finest examples of a group of clinician scientists and

bioengineers working within the ecosystem of a university hospital.

The group aims to bring tissue-engineered bone grafts from the laboratory to clin-
ical practice, by including scaling up, reproducibility, quantification, quality control,
surgical training, and economic feasibility as a part of the translational programmes.
The group’s areas of focus are fundamental science, translation of scientific find-
ings into manufacturing processes, clinical translation, and development of enabling
technologies, such as computer modelling, imaging, bioreactors, and sensing. In the
first phase, clinically relevant in vitro and in vivo screening tools for the quantita-
tive evaluation of potential bone growth-stimulating compounds (cells, signalling
molecules, materials/coatings, and drugs) are being developed. In the second phase,
these tools will be used to produce and to validate bone tissue engineering concepts.

4.1.2 McGowan Institute for Regenerative Medicine,

University of Pittsburgh, USA

The McGowan Institute is a multidisciplinary network of over 250 faculty members

whose primary academic appointments are in 32 different academic departments
of the University of Pittsburgh. The institute has multiple programmes, which are
aligned in four pillars, namely, tissue engineering, cell-based therapies, medical
devices and artificial organs, and clinical translation. There is a strong commit-
ment to ensuring that the technologies developed by McGowan-affiliated faculty are
commercially/clinically available.

To date, there are 31 start-up companies that are the result of technologies
developed by McGowan-affiliated faculty.

The key areas, that are being explored, include biomaterials science, and organ
engineering—either via 3D printing, or decellularised organs.
92 4 International Status

4.1.3 ‘Cúram - Centre for Research in Medical Devices’,

NUIG Galway, Ireland

The Cúram centre is a national centre, which hosts collaborations across 61 academic
leads, 500 researchers, 8 clinicians, and 6 universities. The clinicians are the key
opinion leaders and have led medical device trials. Cúram collaborates with 28
industry partners, 10 multinational corporations and 18 small-to-medium scale enter-
prises. The centre has 406 academic collaborations globally. The centre’s vision is
to develop affordable, innovative, and transformative device-based solutions to treat
global chronic diseases (see Fig. 4.1). The clinical areas of interest at the Cúram
Centre are respiratory, neural, cardiovascular, musculoskeletal, renal and urology,
and soft tissue. These areas have been selected based on the presence of academic
expertise in the area, relevant industries in Ireland and key opinion leaders in the
area.

The Cúram Centre is based on the premise that industry is central to drive the
translation of research into the next generation of medical devices and implants.

Fig. 4.1 Overview of research areas of the Cúram Centre

4.1 Global Landscape of Biomaterials Research Consortia 93

4.1.4 Wyss Institute at Harvard University, USA

Harvard University’s Wyss Institute is a signature example of a coexisting community

of scientists, clinicians, entrepreneurs, and business executives.

The institute is focused towards promoting biomedical products through stages

up to commercialisation, based on a model for innovation, collaboration, and
technology translation.

The Wyss Institute focuses on developing new bioinspired materials and devices
for applications in healthcare among other areas. The Wyss Institute currently has
18 core faculty members and 15 associate faculty members from Harvard and its
partner institutions, who are leaders in the field of biologically inspired engineering.
Technical scientists and engineers from the advanced technology team bring
industrial experience in product development and team management to the Wyss
Institute. The team helps to build and lead integrated technology development teams
focused on high-value applications. The ‘machine shop’ hosts full-time engineers and
houses state-of-the-art manufacturing equipment that enables fast prototyping and
construction of devices. The institute’s business development team as well as experi-
enced entrepreneurs-in-residence (EIRs) facilitate the translation of the technologies
from the laboratory to commercialisation. The team also assists with intellectual
property, technology licensing, and/or start-up company opportunities, and develops
collaborations and strategic partnerships with industry, clinicians, and entrepreneurs
(see Fig. 4.2). Strong collaborations with industry partners enable the understanding
of markets and user needs to match the breadth of applications, envisioned by institute
researchers.

4.1.5 Centre for Translational Bone, Joint, and Soft Tissue

Research, TU Dresden, Germany

The Centre for Translational Bone, Joint, and Soft Tissue Research was established in
2010 to facilitate collaborations among researchers from University Hospital Dresden
and Medical Faculty Carl Gustav Carus of Technische Universität Dresden, Germany.
This centre has a focus to strengthen the experimental research of orthopaedics,
trauma, and reconstructive surgery, and oral and maxillofacial surgery. Around 40
scientists, PhD students, and technicians are working in this centre. The researchers
of this centre work closely with industry and international researchers in translational
research, e.g., 3D bioprinting of tissues in collaboration with Gesim GmbH. At the
centre, the research on 3D bioprinting is focusing on extrusion-based 3D printing (3D
94 4 International Status

Fig. 4.2 Translational ecosystem within Harvard University’s Wyss Institute

plotting) and a 3D bioprinting approach, using micro-algae for medical and biotech-
nological applications. The researchers are also working on therapeutic drug/protein
delivery biomimetic bone matrices and biomaterials for articular cartilage defect
healing.

Bioprinting for space exploratory missions using strontium-substituted calcium

phosphate bone cements is currently being pursued.

4.1.6 Istituto di Scienza e Tecnologia dei Materiali Ceramici

(ISTEC), Faenza, Italy

In the field of regenerative medicine, there are several ongoing programmes at

ISTEC, Italy. A number of researchers at ISTEC are working on the development of
biomimetic materials (3D structures) from bioceramics and hybrid composites (see
Fig. 4.3). The 3D structures are recognised and recruited in the human body by the
natural metabolic processes. Further, they instruct cells to trigger and sustain tissue
regeneration. The biomaterials are developed by novel nature-inspired fabrication
approaches to generate innovative materials capable of smart performance, such as
inherent tissue-inductive and antimicrobial properties with unprecedented mechan-
ical performance. The research on new functionalities, triggering remote activation
4.1 Global Landscape of Biomaterials Research Consortia 95

Biomaterials for Regenerative Medicine

Hybrid Customized
3D printing of Biomimetic
biomimetic nano- Biopolymeric porous ceramic
composites for pastes and bone
and hybrid scaffolds for
multifunctional multilayer cements for
cranial and vertebral
tissue scaffolds
maxillofacial regeneration
regeneration bone regeneration

Hierarchically
organized bone Bioceramic Ceramic and hybrid Smart polymeric
scaffolds scaffolds Biomimetic magnetic implants blends and cross-
obtained by obtained by 3D matrices based on Fe(II-III)- linking agents with
unconventional printing substituted multiple functions
fabrication technologies hydroxyapatite
processes

Biomaterials for Nanomedicine Biomaterials for Skin-Care

Biocompatible
and bio- Bio-hybrid Bioactive multi-
inspired physical filters for doped apatite with
functionalized novel sunscreen multifunctional
micro and lotions with ability
nanoparticles enhanced safety

Fig. 4.3 Research areas of Istituto di Scienza e Tecnologia dei Materiali Ceramici (ISTEC), Italy

and/or enabling in vivo guiding, is a current topic of high interest. This approach,
which involves the recruitment of endogenous biologic factors, paves the way towards
personalised medicine.
Hybrid biomimetic nanocomposites are being developed for multifunctional tissue
regeneration. These are obtained by bioinspired mineralisation of natural polymers
with mineral biomimetic nanophases. The scaffold can be obtained with graded
mineralisation and porosity, to mimic the complex tissue structure of osteochondral
and periodontal regions.

Recently, 3D printing of micro-extrudable ceramic-based, biopolymeric, and

hybrid inks are adopted to develop 3D engineered (stroma-like) organomorphic
scaffolds mimicking the complex architecture of specific bony regions, soft
tissues, and organs.

At ISTEC, customised porous ceramic scaffolds for cranial and maxillofacial bone
regeneration were developed. These were obtained by direct foaming of calcium
phosphate suspensions with rheology optimised to yield final constructs with inter-
connected macroporosity and maximised mechanical strength. Bioactive pastes and
bone cements have also been developed as injectable formulations based on ion-
doped calcium phosphates and natural polymers, targeted to bone regeneration in
96 4 International Status

spinal surgery, orthopaedics and neurosurgery. Hierarchically organised bone scaf-

folds were also fabricated by unconventional processes based on controlled phase
transformation of 3D natural templates occurring at minimal energy and in supercrit-
ical conditions, to obtain bioactive nanocrystalline inorganic phases directly in the
3D consolidated state. Biomimetic ceramic and bio-hybrid matrices were developed
as 3D models of the bone marrow niche for predictive analysis of anticancer therapies
and for testing in situ therapies, employing controlled drug release mechanisms.

4.1.7 3B’s Research Group, University of Minho, Braga,

Portugal

The 3B’s Research Group (3B’s) in the University of Minho, Portugal, is one of the
leading research groups in the world in the field of tissue engineering and regenera-
tive medicine (TERM). The group, founded and directed over the last two decades by
Rui L. Reis, has made long-term, landmark contributions to development of bioma-
terials, biodegradable, natural origin polymers, biomimetics, and stem cell-based
regenerative engineering. The aim of 3B’s is to develop new advanced therapies for
the regeneration of human tissues, and the team comprises an international team of
more than 200 researchers.

Since its foundation, the 3B’s group is recognised for the development of
novel biomaterials (hydrogels, scaffolds, membranes, nano/micro-particles,
smart/functional surfaces) from natural polymers, including marine origin
polymers, for applications in drug delivery and tissue engineering of bone,
cartilage, skin, intervertebral disc, tendon, meniscus, and neurological tissues.

3B’s has founded four different spin-offs companies. The research infrastruc-
ture facilities are specifically designed to execute state-of-the-art tissue engineering-
related research, such as new materials processing, stem cells isolation and
differentiation, and in vitro and in vivo biocompatibility testing.

4.1.8 National Institute of Standards & Technology (NIST),

Gaithersburg, MD, USA

The Alliance for Regenerative Medicine conducted a survey of pharma companies

and found that ‘product consistency and lack of standards is possibly the single
greatest challenge being faced in the field’ of regenerative medicine. Similarly, the
Regenerative Medicine Foundation conducted a stakeholder survey which concluded
4.1 Global Landscape of Biomaterials Research Consortia 97

that the lack of reference materials to benchmark measurements and validation

criteria for critical assays is the most significant hurdle being faced by the industry.
Several standard guides exist that address scaffolds from a generalised perspective.
However, due to the intense interest in fibre-based constructs, there is a need for a
guide that focuses specifically on fibres. The guide will provide a compendium
of techniques for characterising fibre-based constructs and guidance on selecting
appropriate tests based on the application.
Fibre-based constructs include constructs made by electrospinning, forcespinning,
meltspinning, pneumatospinning, extrusion, drawing, and other related processes. A
workshop was held to discuss the guide and to serve as a launching point for the
working group, which currently consists of 33 stakeholders, with the majority being
from industry. A second working group has been formed to develop a standard test
method for measuring cell viability in a scaffold. Tissue-engineered medical products
often consist of cells suspended in a 3D scaffold, and the product’s mechanism of
action may rely on the cells being viable to regenerate tissue. However, the scaffold
hinders cell viability measurements in a variety of ways. Thus, a working group has
been formed to develop a model scaffold-cell-assay system for assessing cell viability
in scaffolds. An interlaboratory study will be used to assess the reproducibility of
the method in different laboratories. Reproducible measurement systems are the key
during biomanufacturing when thousands of units need to be assessed for consistency.
These results will provide a strategy for validating measurements of cell viability in
scaffolds and will support the development of the standard guide.

To address clinically unmet needs, the researchers in the Biomaterials Group

at NIST are leading the development of a new documentary standard guide for
characterising fibre-based constructs for tissue-engineered medical products.

4.1.9 Wake Forest Institute for Regenerative Medicine,

Winston-Salem, North Carolina, USA

The Wake Forest Institute for Regenerative Medicine (WFIRM), USA, is recog-
nised as an international leader in translating scientific discovery into clinical thera-
pies, with many world firsts, including the development and implantation of the first
engineered organ in a patient. More than 450 scientists collaborate on regenerative
medicine research at this institute, the largest in the world. The major achievements
of institute scientists include engineering replacement tissues and organs in four
categories: flat structures, tubular tissues, hollow organs, and solid organs.
WFIRM’s scientists have successfully implanted several tissues and organs such
as skin, urethras, cartilage, bladders, muscle, and vaginal organs, which have been
created in the laboratory using a variety of engineering strategies. To scale up the
98 4 International Status

manufacturing process, WFIRM turned to 3D printing and over many years, the
institute’s scientists have developed the integrated tissue and organ printing system.
They demonstrated that it is feasible to print human scale living tissue structures
that have the right size, strength, and function for use in humans. The scientists have
optimised the water-based ‘ink’ that holds the cells so that it promotes cell health and
growth. They also have printed a lattice of micro-channels throughout the structures
to allow nutrients and oxygen from the body to diffuse into the structures and keep
them alive, while they develop a system of blood vessels.
The institute’s expertise in generating micro-human organs and tissues from the
cellular level to functional tissues led to its selection to lead a $20 million ‘Body-on-
a-Chip’ programme. The goal was to build a miniaturised system of multi-human
organs to model the body’s response to chemical and biological agents and develop
potential therapies. The Body-on-a-Chip platform can accelerate the translation of
basic scientific discoveries into the clinic, in a faster and more accurate way than in
laboratory animals.

The WFIRM team was the first to create miniature tissue equivalents using
regenerative medicine techniques that replicate a high-level, long-term func-
tion, and they were able to combine up to six organs on the same device.

4.2 Multi-institutional Research Initiatives and Training

Centres

4.2.1 Henry Royce Institute, UK

The Henry Royce Institute is a national centre bringing together 800 researchers for
collaborating in the broad area of advanced materials in the United Kingdom. This
institute is founded at the University of Manchester and its research hub is spread
across the founding partners that are the Universities of Cambridge, Liverpool, Leeds,
Oxford, Imperial College London, the National Nuclear Laboratory and the Culham
Centre for Fusion Energy.
The Royce Institute has nine critical research themes, one of which is biomedical
materials. The capability landscape is shown in Fig. 4.4. The aim of the biomedical
materials area is to provide direct patient benefit and to improve medical testing and
device production. An example of an application of biomedical materials would be to
create 3D in vitro tissues that improve pharmaceutical testing and also reduce the need
for animal testing. Key research outcomes or targets include bespoke hard and soft
implants created by additive manufacturing, new multifunctional fibrous scaffolds
for tissue regeneration, new bioelectronic systems, faster biomedical device testing
facility, minimally invasive tissue repair, and smart materials for remote sensing or
monitoring (e-health).
4.2 Multi-institutional Research Initiatives and Training Centres 99

ADDITIVE
MANUFACTURE
Ti Alloy orthopaedic
screws,
Cellular therapies,
Injectable Stents

Light
In vivo Sheet
Improved
probe
Manufacture and FIBRE
BIOELECTRONICS/
Analysis TECHNOLOGY
SMART MATERIALS
Drug elu ng stents, Wound care dressing,
Neural network ↑ Throughput Tissue engineering
interfacing devices ↑ Resolu on scaffolds

CQ1 ↑ Reproducibility Imaging

imager Suite

3D TISSUES
Tissue engineered
constructs,
Improved human ssue
transplants

Fig. 4.4 Capability landscape of the Henry Royce Institute (adapted from original figure from the
Henry Royce Institute)

The focus of the Royce’s Biomedical Materials area is Fibre Technology,

Bioelectronics Medicine, Additive Manufacturing and product scaling up to
TRL 5 Level.

4.2.2 Matériaux pour la Santé (MatSan), France

MatSan is the French ‘Materials for Health’ commission. MatSan gathers together
more than 65 academic and over ten industrial centres, as well as clinicians. The
research themes include bioceramics/bioactive glasses and mineral/organic compos-
ites for bone regeneration, (bio)polymers and hydrogels, stimuli-responsive poly-
mers for (soft) tissue repair, metals and alloys for bone implant applications, cancer
treatment, medical diagnosis, additive manufacturing, coatings, injectable pastes,
biomimetism, the study of biomineralisations, and exploration of biological tissues.

Special attention is paid to the synthesis of biomaterials and their precursors,

which may be metastable, to their physical–chemical characterisation, their
processing (dense or porous scaffolds, films and coatings, injectable pastes,
100 4 International Status

additive manufacturing/3D printing, colloidal particles, etc.), and the property

evaluation (durability/ageing, biocompatibility, etc.).

On a collaborative note, MatSan regularly organises international and national

conferences, thereby increasing the visibility of the French community towards
other partners, including foreign researchers and industrial representatives. MatSan
includes four national-scale scientific societies—the French society of Metallurgy
and Materials (SF2M), the French Group of Ceramics (GFC), the French Center for
anti-corrosion (CEFRACOR) and the French “Titanium” association.

4.2.3 Materials Assembly and Design Excellence in South

Carolina (MADE in SC), Clemson University, USA

Materials Assembly and Design Excellence in South Carolina (MADE in SC) is

a new five-year venture, established in September 2017, with funding from the
National Science Foundation. The overarching vision of the programme is to create
a global materials innovation hub as a statewide effort with ten participating insti-
tutions in South Carolina. Nearly, over 65 faculty members are engaged in training
and mentoring of research scholars (40 undergraduate and 30 graduate per year) and
post doctoral researchers. Additionally, it also provides training and mentoring of
STEM high school teachers, partnerships and collaborations among team members
and external partners, and shared materials research infrastructure. The focus is on
multi- and inter-disciplinary research with three major thrust areas, which are unified
by an integrated modelling and computational core (Fig. 4.5).
Thrust 1 is on hierarchical organic and inorganic complexes of materials, primarily
for enhanced optical, electrochemical, and magnetic properties. Thrust 2 is on soft
materials, mainly polymers. The emphasis is on designing stimuli-responsive poly-
mers, that can interact and respond to the changes in their environment. For example,
pH-responsive polymers and hydrogels for wound healing is one of the focal areas.
Thrust 3 is on rational design of biomaterials. The focus areas of this thrust are
synthesis and biogenic assembly, integration of biomaterials into micro-engineered
devices and biological test beds.

A second area of interest at MADE in SC involves the design of micro-

engineered platforms to investigate the responses of cells to topology, mechan-
ical forces, and electric fields and development of 3D constructs from extruded
biomaterials.
4.2 Multi-institutional Research Initiatives and Training Centres 101

Fig. 4.5 Overview of the scientific areas of the MADE in SC initiative (Image courtesy Rajendra
K. Bordia)

4.2.4 ARC Training Centre for Innovative Bioengineering,

University of Sydney, Australia

The Australian Research Council (ARC) training centre for innovative bioengi-
neering is devoted to address the uprising need of personalised medicine for the
diverse age groups in the growing population of Australia. ARC training centre’s
goal is to bring together early career researchers, industries, and hospitals to inno-
vate new technology followed by translating those towards ‘new treatments’. The
centre is spearheaded by threefold goals, ‘advance training’, ‘develop and support
students’, and ‘help students find their place’. At present, the ARC-sponsored centre
functions in close collaboration with seven universities and five industry partners.
There are three prevalent research themes in the ARC training centre. The theme
‘technologies’, where the primary research interest is focused mainly on ‘pioneering
diagnostic therapeutic wearable and implanted technologies’ is accompanied by
the second research theme of ‘innovative biomaterials’. The development of new
advanced biomaterials, design, and fabrication is one of the basic research inter-
ests in this division. ‘Sensors and telemetry technologies’ is the third category of
the threefold research theme, where the ‘continuous’ evaluation and optimisation of
future implants are being performed. In terms of training, there are currently two
‘training themes’ available in ARC, namely TT1 and TT2.
102 4 International Status

In TT1, the centre provides hands on training in translating new technology

into an industry setting, while TT2 provides frameworks for developing routes
to market for innovative biomedical technology solutions.

4.3 Closure

In developed nations, a better research ecosystem not only enhances research output
but also allows proximity of researchers to patients undergoing clinical trials. In Asia,
we can see an opportunity to better the innovation ecosystem.
Examples of well-developed regulatory frameworks are CE and FDA approval,
which are followed in the western world. The developed nations are seen to have
better connections among academia, companies and contract research organisa-
tions (CROs). Many large programmes in Europe and North America often attract
significant funding from private companies.
Transforming India’s innovation ecosystem requires due thought and careful plan-
ning. In order to achieve a more robust and resilient research ecosystem, sustained
efforts are needed to emulate the best practices and policies of well developed ecosys-
tems, while adapting these to the Indian context. For this purpose, I present an
overview of the challenges involved, and also key recommendations for the path
ahead, in Chaps. 5 and 6, respectively. A key part of improving the research ecosystem
is improving the education system which supplies the human resources. This will
be discussed in further detail in Chap. 6. I envision that together, all stakeholders
can make concerted efforts towards ensuring that the Indian research ecosystem
attracts and retains the best talent, and harnesses its collaborative synergies towards
addressing the challenge of providing high quality affordable healthcare. Unmet
needs have historically driven many great scientific discoveries. Now is the time for
us to discover not only such discoveries, but also the full potential of a robust research
ecosystem that can become a role model for many developing countries. It is hoped
that the next two chapters will encourage greater dialogue on this subject, and that
the actionable suggestions presented will be of help in this respect.
Chapter 5
A Challenging Frontier and Status
of National Policies

Abstract It is hard enough to mimic, predict, and create the intricate and elegant
structures of living tissue or organs and harder still to make them sustainable and
affordable for the common man. Over the years, the field of biomaterials science
has blossomed with impressive strides in establishing connections with nanoscale
science, genetics, and molecular and cell biology. Along with the coming together
of multidisciplinary teams of physicists, chemists, biologists and engineers; new
opportunities for understanding, manipulating, and mimicking biological materials
and processes have opened up. With unique materials and devices, biomaterials
have emerged as a frontier science, challenging the very foundations of accepted
paradigms and pushing the boundaries of existing knowledge, especially around its
interface with human health.

© Springer Nature Singapore Pte Ltd. 2020 103

B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0_5
104 5 A Challenging Frontier and Status of National Policies

As discussed in Chap. 2, the global markets for biomaterial implants in different

segments like orthopaedic and dental implant/device segments are expected to
increase steadily in the coming decade. Yet, the march of science is fraught with
challenges. Although in the past few decades, the focus on patient-specific solutions
has risen extensively, there are worrying questions that refuse to go away: How can
scientists tap into the enormous unaddressed potential of biosystems and biomateri-
alomics? How far can clinical and societal needs be best met? What biological strate-
gies would lead to materials that build and repair themselves? How can biomaterials
be made multifunctional, dynamic, responsive and sustainable?
A few developing nations like India and China have seen a significant improve-
ment in the quality and efficacy of healthcare due to gradual acceptance of imported
implants and biomedical devices and procedures for diagnostics, treatment, and
patient care, in the last few decades. But the cost of quality healthcare has esca-
lated tremendously; how can scientists design and develop applications so that the
healthcare solutions reach the economically challenged cross-section of society?
While addressing many such unanswered questions, this chapter summarises some
of the major challenges.

5.1 Accelerating Regulatory Approval

In India, access to affordable medical devices and healthcare facilities is still a major
problem. Current challenges are collaboration among biomaterial scientists and clin-
icians, translation of research from prototype stage to functional products, costly
imported biomedical devices and viable technology and manufacturing scale up of
academic research outputs by biomedical entrepreneurs.

A strong regulatory framework is of immediate importance in India, since

Indian companies need to obtain CE or US FDA approvals to penetrate into
global markets. In India, there is a need for enforcement of standards to ensure
that product quality and patient safety remain uncompromised.

5.1.1 Current Status and Gaps in Medical Device

Certification

To improve access to safe, accessible, affordable, and appropriate medical devices,

a number of policies and related teams have been implemented since 2014. These
include the Medical Device reform task force (2014/15), Inverted Duty Correction
for spared/components (2016), Medical Device Rules (2017), preferential procure-
ment of domestically manufactured goods, GFR (2017), Medical Devices R&D
5.1 Accelerating Regulatory Approval 105

priority and market access think tank- KIHT (2017), Code for Marketing Practices
(2017), Medical Devices Promotion Council (2017), and Medi Valley (2018). Also,
the government is thinking of creating a separate Ministry of Pharmaceuticals and
Medical Devices to serve the sector in a more integrated manner.

The Medical Devices Rules (2017) stipulated the rules for manufacturing,
import and sale of medical devices, as well as for clinical trials, labelling, and
inspection.

Effective from 2018, it is expected that Medical Device Rules will bring the regu-
latory system in India to be on par with global standards. Medical devices will be
classified on the basis of risk: high-risk devices are to be regulated by the Drug
Controller General of India (DCGI) and low-to-moderate risk devices are to be regu-
lated by the appropriate state authority. The devices should conform to specific stan-
dards applicable, e.g. ISO. It is also indicated that the shelf life of the devices should
not exceed 60 months, unless satisfactory evidence is provided by the manufacturer
to justify an extension.
Regarding quality certification for medical devices in India, the Association
of Indian Medical Device Industry (AIMED), in collaboration with the Quality
Council of India (QCI) and the National Accreditation Board for Certification Bodies
(NABCB), is implementing a voluntary quality certification scheme for medical
devices, known as the Indian Certification for Medical Devices (ICMED) Scheme.
The scheme is expected to instill confidence among buyers, while diminishing the
credibility of substandard products.
In the above context, KIHT’s Non-regulatory Innovation Potential Utility and
Novelty Certificate (NIPUN) is the first ever indigenous testing and certification
programme for medtech innovations to access the Indian market. The NIPUN
scheme provides help in business plan analysis, quality compliance, testing, rapid
prototyping, and market access.

DBT-BIRAC recently initiated the National BioPharma Mission (including

Medical Devices), whereby industry-academia consultation paved way for
government funding in the health technology sector.

The South East Asia Regulatory Network (SEARN) is responsible for regulation
of medical products, including medicines, vaccines, biological, and medical devices
and diagnostics for human use in the eleven countries of the South East Asia Region.
The Central Drugs Standard Control Organization (CDSCO) is the national regu-
latory body for Indian pharmaceuticals and medical devices. To advise CDSCO on
matters related to the regulation and implementation of medical devices, the Union
Health Ministry has constituted a special committee, the Medical Devices Technical
106 5 A Challenging Frontier and Status of National Policies

Advisory Group (MDTAG) in 2019. Besides the Chairperson and the Member Secre-
tary, 22 other members constitute the committee from various departments containing
representatives from organisations, including Department of Science and Tech-
nology (DST), National Institute of Biologicals (NIB) and Indian Council of Medical
Research (ICMR) and Association of Indian Medical Device Industry (AIMED),
Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST),
IIT Delhi, Association of Diagnostics Manufacturers of India (ADMI), Bureau of
Indian Standards (BIS), Medical Technology Association of India (MTAI), Atomic
Energy Regulatory Board (AERB), Defence Research and Development Organi-
zation (DRDO), Department of Electronics and Information Technology (DEITY),
National Health Systems Resource Centre (NHSRC), Federation of Indian Cham-
bers and Commerce Industry (FICCI), Confederation of Indian Industry (CII), and
American Chamber of Commerce in India (AMCHAM).

The mandate of MDTAG is to discuss issues relating to the implementation

of Medical Devices Regulations, while aiming to strengthen the regulations
to make medical device companies accountable for quality and safety of their
products.

Further, they will take up matters with the Drugs Consultative Committee (DCC)
and Drugs Technical Advisory Board (DTAB).

5.1.2 Manufacturing-Related Regulations

It is mandatory that the manufacturers of the biomedical implants and devices follow
ISO 13485:2016, an international standard to ensure the compliance with Good
Manufacturing Practices (GMP), which governs the medical devices quality manage-
ment systems for regulatory purposes. The standard had undergone a major overhaul
in 2016. The emphasis of the regulators used to be more on design, design risk and
design validation and complaint management, with less emphasis on manufacturing.
However, a shift happened to place more emphasis on analysing the manufacturing
risks (PFMEA) and identifying the methods to prevent problems from happening
(risk management and control). The standard governs all activities of the product life
cycle, from conception to disposal.

Three key aspects of the ISO 13485:2016 standard are validation, evidence,
and contamination control.

The aim of validation is to certify that steps in the routine manufacturing process
will not go wrong. Validation requires submission of a process map, process risks,
installation qualifications for equipment, critical process parameters that influence
5.1 Accelerating Regulatory Approval 107

outcome, definition of worst-case parts with rationale, acceptance test methods,

process challenge at extremes of process limits, and process limits set as the control
limits for routine production. The particular requirements for implantable medical
devices are that the organisation must provide records of components, materials, and
conditions for the work environment used. Typically, precision machining is used
for biomedical implants.

Most implants include few critical features with tolerances of less than or equal
to 0.05 mm.

Validating machining process is optional, if 100% verification is practiced.

Notably, many companies choose to validate the machining process to reduce the
inspection burden. For cleaning and passivation, validation is mandatory. This is
an area, where the respective regulatory professionals are going through advanced
training. For proving cleanliness, one has to prove that there are no contaminants from
the manufacturing process and also from the cleaning process. Residues should be
negligible or within safe limits. Also, the manufacturing process should not adversely
affect biocompatibility.
Accelerated ageing, drop testing, and sterility testing are some of the methods used
to test packaging, so that reliable data can be provided to justify the indicated shelf
life. Regarding sterilisation, typical methods include gamma irradiation, ethylene
oxide gas, and gas plasma (H2 O2 ). The selection of a specific sterilisation protocol
depends on the type/composition of the implant. Validation of sterility assurance
level is mandatory.

5.2 Strengthening Basic Research in Biomaterials Science

The human body has limited ability to induce self-repair and regeneration. Various
tissues of the musculoskeletal, nervous, cardiovascular and urological systems
rarely achieve functional regeneration, post-injury. Multifunctional biomaterials with
tissue-specific biocompatibility are clearly needed.

One of the unique challenges therefore lies in identifying new biomaterials

beyond the limited range, currently licensed for use in humans.

In the context of the evolution of biomaterials, the first generation of bioma-

terials was used to achieve a combination of physical properties to match those
of the tissue being replaced, with minimal host response. Examples include high-
strength materials such as titanium and steel, as bone implants. While developing
second-generation biomaterials, importance was given to materials that could elicit
a desired response in a controlled physiological environment, while simultaneously
108 5 A Challenging Frontier and Status of National Policies

minimising the immune response. There has been an increasing need to develop
biomaterials with multifunctional properties that can facilitate a more natural way
for repair and regeneration of host tissues.

Third-generation biomaterials are designed to elicit specific reactions at cellular

and subcellular levels.

5.2.1 Development of Next-Generation Biomaterials

The biggest challenge lies in developing high-quality indigenous biomedical

implants, in a field that is growing faster due to technological advancement and
societal needs. Nearly 6 million people die each year as a result of injuries, a global
public health problem. And the number of people at very advanced age, globally,
is surging, projected to triple between 2017 and 2050. Implants cater to over 2
million such people every year, whose quality of life gets compromised by debili-
tating injuries. They need medical implants of excellent biocompatibility, superior
corrosion resistance, and high strength-to-weight ratio. Also, the number of revi-
sion surgeries has increased at about the same rate as that of primary surgeries,
largely due to prosthesis failures. More than 30% of the failures are directly due to
post-surgical infection (Fig. 5.1). To avoid this, on-site delivery of antibiotics during
post-surgery period is one of the clinical options. A summary of the ethical and safety
considerations of biomaterials research is provided in Appendix B.

a b c

Fig. 5.1 Infected total knee replacement second-stage operation: Initial treatment carried out with
long-term antibiotics due to medical risk assessment. Two-stage revision planned due to progressive
loosening. (a) Intra-operative X-ray clinical image, (b) Post-operative X-ray image to reveal soft
tissue, (c) Six month post-operative X-ray to show full absorption and infection-free state
5.2 Strengthening Basic Research in Biomaterials Science 109

This clinical challenge can be alternatively addressed by modifying metallic

implants to release drugs, post-implantation, without affecting their structural,
mechanical and biological attributes.

It has been anticipated that by 2030, the demand for primary THR will increase by
171% for patients with less than 65 years of age. In 2015, among all joint replacement
procedures, total knee replacement (TKR) showed the highest market contribution.
The number of TKR surgeries is expected to increase by 4 million cases by 2030,
exclusively in USA. In spite of overwhelming accomplishments, the natural joint-
like functioning of UHMWPE has not yet been achieved in many applications (viz.
hip, knee, shoulder, elbow, ankle and spine), due to performance-limiting clinically
relevant properties, especially aseptic loosening due to wear.

A better clinical outcome in many musculoskeletal surgeries demands the

development of UHMWPE-based hybrid composites, either blends with
another biocompatible polymer, or with carbonaceous reinforcements to
enhance wear resistance property.

With respect to implants, the selection of biomedical grade raw materials is impor-
tant in producing desired products. For bioceramic implants, grinding and polishing
are critical challenges for production, and appropriate machinery needs to be estab-
lished for THR implants. Furthermore, addressing the stiffness mismatch between
the implant and surrounding bone is of major concern since it can result in osteolysis,
or active resorption of the bone by osteoclasts (Fig. 5.2).

a b

Early sign of Failed implant

osteolysis due to bone loss.

Fig. 5.2 (a) Diseased hip joint, (b) Stiffness mismatch and failure of implants (post-operation
radiography images)
110 5 A Challenging Frontier and Status of National Policies

In the case of the musculoskeletal implants, the subject-specificity and bone

condition are to be critically considered, while designing the next-generation
implants.

In order to address such challenges, a new generation of acetabular liners or dental

implants are to be developed and clinically tested. Another area in orthopaedics,
where biomaterials play an important role, is the use of calcium phosphates as bone
filler in orthopaedic/dental surgery or as bone cement or for drug delivery appli-
cations. An important challenge here is the prediction and validation of sustained
drug release from nanomaterial scaffold-based delivery systems for treatment of life-
threatening diseases, including cancer. Researchers from pharmaceutical sciences
can play a major role in this, from the development of drug-eluting coronary stents,
drug- releasing orthopaedic devices to tissue engineered scaffolds for targeted drug
delivery applications.
Several Indian research groups are currently working on doped hydroxyap-
atite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP) for
orthopaedic and dental applications. Doped HA-based materials have been developed
for drug delivery and hyperthermia treatment in cancer therapy, too.

While several competing wet chemical synthesis processes using synthetic

chemicals or biogenic minerals are being investigated, it is important to develop
commercially scalable synthesis techniques to develop products—powders,
granules, and porous blocks—made of materials like hydroxyapatite for various
medical applications.

5.2.2 Biomaterials and 3D Bioprinting-Based Approaches

for Regenerative Engineering

Due to accidents or diseases, humans often undergo traumatic injuries in their lives
which lead to loss of function in many tissues and organs. However, the supply of
donor organs is limited. It becomes an arduous task to supply healthy organs to large
numbers of patients, who require transplants. A number of research groups in India
and abroad are working towards the use of functional biomaterials-based platforms,
and further combining of these platforms with stem cell-based therapies to mimic
the natural micro-environment of the body. The functionalities of such platforms
provide 3D matrices with desired porosities, elasticity, and wettability along with
topographical cues that favour cellular attachment, growth, and differentiation, as
well as proper nutrient flow for tissue regeneration. With respect to cartilage tissue
engineering, cell implantation within the articular joint poses several problems. Also,
5.2 Strengthening Basic Research in Biomaterials Science 111

optimisation of scaffolds for cartilage tissue is needed, together with a good fit of
the scaffold to the perimeter of the defect. Maintaining the desired hyaline cartilage
phenotype is also another challenge.

Although, several impressive tissue engineering approaches have been reported

in the field of regenerative engineering over the past decades, successful transfer
of these results into clinical trial evaluation still remains a challenge.

Biofabrication is an emerging field, wherein complex biologically functional

tissues are fabricated using extracellular matrix, growth factors, living cells and
biomaterials. The aim is to fabricate native-like tissue structure or organs, with
specific dimensions and high reproducibility by 3D printing. 3D bioprinting tech-
niques are the most recently developed biofabrication approaches in which pore
geometry, distribution, and interconnectivity with precise deposition of cells within
the patient specific scaffold geometry can be fabricated to improve cell signaling,
cell-cell and cell-ECM interactions, cellular viability and functionality within the
bioprinted construct. Bio-inks are the cell-laden biomaterial that can be inte-
grated into the additive manufacturing process to mimic the extracellular matrix
environment and support the living cells so that cell adhesion, proliferation, and
differentiation take place within the 3D printed construct.

To investigate the modulation of innate immune response, macrophage

polarisation pathways can be explored in tailoring the vascularisation of
scaffolds.

At several IITs, different research groups (S. Ghosh in IIT Delhi, R. Banerjee in
IIT Bombay and S. Dhara in IIT Kharagpur) are working on synthetic and natural
polymers for tissue engineering and regenerative engineering applications. In this
context, the modulation of viscoelastic property is one of the essential pre-requisites
to regulate the cell functionality for regenerative medicine. The use of microrheology
techniques, like DWS needs to be used in this context.
In evaluating the biocompatibility, the researchers mostly use conventional petri
dish culture of single cell type (osteoblasts, fibroblasts, chondrocytes, Schwann cells,
neuroblastoma, etc.), in vitro. It is important to understand cellular changes at the
gene-level, and how the cells sense cues in the cellular micro-environment on a
biomaterial platform. Biomaterials researchers use several biochemical assays for
cytocompatibility without focusing much on cell signaling pathways. The experi-
ments involving co-culture under physiologically relevant conditions are also not
widely conducted in the field of biomaterials science. While significant efforts are
underway to develop tissue engineered scaffolds for organ bioengineering appli-
cations, the immunogenicity of synthetic biomaterials, eliciting innate or adaptive
immune response, is not widely explored.
112 5 A Challenging Frontier and Status of National Policies

With respect to the neurosurgical application, peripheral nerve injuries (PNIs) are
a very common type of nerve injury, and restoration of such kind of nerve damage
remains a greater challenge in the field of regenerative engineering (Fig. 5.3). The
conventional clinical treatment has many limitations and disadvantages, such as
improper fitting and loss of native functionality, donor site morbidity, pre-existing
injury to the donor nerve, donor-host mismatch and host immune response.

For neurosurgical treatments, the development of nerve conduits of gaps larger

than 10 mm remains a challenge.

Fig. 5.3 (a) Overview of the anatomy of the central nervous system (CNS) and peripheral nervous
system (PNS). (b) Peripheral nerve injury (Source Mayo Foundation). (c) 3D bioprinting approach
for biofabrication of a nerve conduit for peripheral nerve repair (Hu et al. 2016). (d) Nerve graft
approach for peripheral nerve repair (Source Mayo Foundation)
5.2 Strengthening Basic Research in Biomaterials Science 113

Therefore, future research aims should be directed to develop an artificial

nerve conduit for the substitution of injured peripheral nerves with patient-specific
architecture, optimum mechanical properties, conductivity, and biodegradability.
In the field of urological reconstruction, defects of the human urinary bladder
and urethra result from cancer, tumour, loss of elasticity, insufficient capacity
(for bladder), and detrusor compliance. These are common and serious problems,
specifically in the elderly patients.

The repair and restoration of human urothelial tissues are challenging problems
due to the extremely weak regenerative tendency of urothelial cell lines.

Concerning the urological pathologies, bladder carcinoma (BC) generally orig-

inates in urothelium. Subsequently, the tumour invades the detrusor muscle layer,
leading to what is clinically known as muscle invasive bladder cancer (MIBC). As
per the available statistics, around 25–30% of all the bladder cancers is MIBC, which
necessitates surgical intervention to partly or completely remove the bladder tissue,
in an effort to restore the normal urological physiology. In addition, neurological
conditions and congenital bladder anomalies result in a functionally deficient urinary
system.
The typical procedure for end stage bladder disease involves replacement or
augmentation with a section of the patient’s gastrointestinal tract as an autologous
graft. Despite significant efforts to develop biomaterials for urinary bladder recon-
struction, autograft of the ileum still remains as ‘gold standard’, due to the lack of
acceptable clinical performance of synthetic products.
The primary challenge in the development of biomaterials for urological recon-
structive applications is to use two different cell lines in different hierarchical tissue
layers, since the inner surface of urological tissues contain the urothelial cell lines
and the smooth muscle tissues are present in the outer surface. Therefore, future
bioprinting strategies must fabricate bilayered scaffolds for bladder reconstruction
or a cylindrical urethra. To achieve appropriate tissue extensibility compared to
native bladder tissue, selection of fabrication approach and choice of materials are
important.

5.2.3 Multiscale Computational Analysis

The use of calcium phosphate in clinical applications was highlighted earlier in

this chapter. For (multi)-ion doped calcium phosphate bioceramics, the local chem-
ical environment surrounding the dopant in HA/TCP-lattice structure governs the
dissolution of ions, which significantly influences the biomineralisation and cell
functionality. It is important to pursue ultrastructural and computational analyses to
correlate combinatorial research involving micro-structure with functional proper-
ties and biocompatibility to allow better control over structure–property correlation
in bone-mimicking materials.
114 5 A Challenging Frontier and Status of National Policies

The recent results from several Indian research groups suggest that the modulation
of stem cell fate processes can be achieved by stimulating them with endogenous
bioelectric fields. However, several key questions remain to be answered. These
questions are related to the specific mechanisms of stem cell activation by external
electrical stimuli.

Significant lessons are to be learnt by correlating the electric field parameters

and level of tissue or substrate conductivity required to trigger differentiation
of choice, if these variants function in harmony to govern stem cell behaviour.

Through the research of IISc/IIT (BHU) researchers, piezoelectric and conducting

materials, in addition to external stimulation (mechanical and electrical), form the
basis of new, interesting and efficient strategies for bone tissue engineering and
regenerative medicine applications. Owing to the number of advantages associated
with piezoelectric biomaterials (piezoelectricity, pyroelectricity and ferroelectricity),
and biological (poling-induced mineralisation and cellular) response, it is envis-
aged that piezoelectric biomaterials could serve as orthopaedic implant materials in
the near future. IISc/IIT (BHU) researchers have developed electric/magnetic field
stimulation protocols to modulate cell functionality on several biomaterials.

The fundamental principles that drive the synergistic interactions among

substrate properties and stimulation parameters to govern cell-material inter-
actions are still unknown.

This is also an area, which can be benefitted by multi-scale computational anal-

ysis. Also, more pre-clinical studies conducted on piezobiomaterials in larger animal
models, followed by clinical trials in human subjects are needed.
The interaction between biomolecules (proteins) and the biomaterial surface needs
to be probed at a single molecular level, using computational tools, like, MD/Monte
Carlo simulation. This is the key step governing the cell-material interaction.

Despite the recent focus at the interface of biology and engineering in

academia, India lacks extensive coordinated translational research programs
on biomaterials and implants.

For this, there are several bottlenecks that need to be dealt with. A major challenge
in the field is that it is largely based on experimental findings, based on multi-
scale and multidisciplinary measurements—electron microscopy, micro-computed
tomography for 3D micro-structure analysis, cell viability and differentiation assays,
and pre-clinical and clinical outcome assessment. Less effort, however, has gone into
5.2 Strengthening Basic Research in Biomaterials Science 115

multi-scale models: molecular dynamics, micro-mechanical finite element models

and so on.

5.2.4 Data Science Driven Approach

Despite several decades of research, we still do not have proven capability to

predict how to design biomaterials that are capable of interacting specifically with
the biological system of a patient. The concept of biomaterialomics would allow
us to analyse and integrate existing computational tools with the knowledge of
biomaterial ‘genes’ and accelerate the process of biomedical device innovation. The
‘genes’ of biomaterials would include the structure and properties. In line with the
existing concepts of ‘proteomics’, ‘genomics’, and ‘materials genome’, the alterna-
tive phrases to describe the above concept can be ‘biomaterialome’, ‘biomateriome’,
or ‘biomaterials genome’.

After an extensive discussion among the thought leaders in the area of bioma-
terials science at Chengdu, China, in June 2018, the term ‘biomaterialomics’
was conceived and defined as the ‘integration of computational tools, large
databases and experimental techniques, to explore the basic material elements
and combine them to discover and design new biomaterials for medical
products.’

This concept would be based on the application of the theory and technology of
materials genomics to biomaterials.
The conventional approaches in biomaterials science or bioengineering involve the
intuitive way of tailoring process variables that often incur long development cycles
and high costs (Fig. 5.4). Against the backdrop of the ever-increasing unmet clinical
needs, it is therefore important to develop patient-customised, implantable bioma-
terials or biomedical devices in an accelerated manner to accomplish the bedside-
bench-bedside translation cycle. Building on the concepts of the Materials Genome
Initiative, it is recommended to adopt ‘biomaterialomics’. This new concept should
rely on a data-driven, integrated understanding of biocompatibility, and elements of
biomaterials development. The newer computational approaches to establish process-
structure-property (PSP) linkages, established in the field of materials science for
structural materials, can play significant roles in developing the biomaterialomics
concept.
It should be emphasised here that the biomaterialomics approach can significantly
aid in the development of new-generation bioimplants, whose predictive clinical
performance would be closely tracked by ‘digital twins’. An example is provided
in Fig. 5.5, which also presents a new concept, as how computational data science
based approaches can be merged with experimental and multiscale physical modeling
approaches in near future.
116 5 A Challenging Frontier and Status of National Policies

Quantum of data

Defining
clinical Product in
needs market
1 2 3 4 5 6 7

Lab-scale in vitro Pre- Device Clinical Product Regulatory

development testing clinical prototype trials scale up approval
study
Regulatory approval/ Clinical significance

Fig. 5.4 Typical innovation workflow in biomaterials/biomedical device development, showing

the qualitative trend in quantum of data and clinical significance at various phases

Experimental Tools Computational Tools Data Science and

High throughput prototyping of sample Multiscale physics-based Informatics Tools
libraries models for studying PSP Data management
Multiscale microstructural characterization linkages (e.g. FEA, Phase- Analytics (e.g. Machine
Multiresolution mechanical characterization field, MD Simulation) Learning,
Quantitative analysis of cytocompatibility, Biomechanical performance Deep Learning)
hemocompatibility and bactericidal property simulation Fusion Science – Bayesian
Pre-clinical study to assess whole organism framework
response e-Collaboration
Clinical trials to assess human response

Fig. 5.5 Summary of the major elements used to build a biomaterialomics framework

To substantiate further, Fig. 5.6 presents the concept of the machine learning (ML)
algorithm, which can be adapted to accelerate the discovery of new biomaterials. The
quantum of high-quality data required in the ML approach unfortunately requires
significant experimental efforts, including many control experiments.

The Biomaterialomics approach will bring together concepts and ideas from
artificial intelligence (AI), machine learning, deep learning, etc., and will
combine with the results of the computational approaches (e.g. FEA-based
biomechanical analysis or MD simulation results) employed in the field of
biomaterials science.
5.3 Building Translational Research for Human Healthcare 117

Fig. 5.6 Overview of the machine learning approach, which can be employed in the field of
biomaterials science

5.3 Building Translational Research for Human Healthcare

Translational research converts ‘bench’ basic research discoveries into products that
can be used at the ‘bedside’ of a patient in a hospital clinic, as part of healthcare
treatment and prevention. Translational research involves researchers, clinicians,
start-ups, industries and policy makers.

The domain of translational research aims to improve the accessibility of

healthcare by accelerating scientific discoveries related to biomedical implants
and biomaterials from the institutional laboratories to clinical trials and then,
the transfer of the technology to start-ups and industries.

Here, the institute network in the Indian context can comprise of academia,
start-up companies, constituent laboratories of Council of Scientific & Industrial
Research (CSIR), Department of Science and Technology (DST) and Department of
Biotechnology (DBT), DRDO/DAE laboratories and regulatory consultants.

The very first stage of this translational research is the identification of the
unmet clinical need and the human disease model.

Once the problem is recognised, it is taken up by the institute networks, as

mentioned above. The project teams in the institute network, which includes faculty
members, project researchers, graduate students and consultants or entrepreneurs,
118 5 A Challenging Frontier and Status of National Policies

work on it to build a prototype. At this stage, the prototype is not ready for
implantation in humans, because of the need of testing in controlled laboratory
settings.
Government agencies and regulatory bodies such as ISO and the FDA (Food
and Drug Administration) provide procedures, protocols, guidelines, and standards
that need to be used for biocompatibility evaluation of newly developed materials.
ISO recommends standards depending on the nature and duration of the contact of
a biomaterial with an osseous system. The guideline, ISO 10993-Part 1, provides
methodology for choosing the proper biological evaluation tests. It also includes
vital information about positive and negative control materials, extraction conditions,
choice of cell lines and cell media, as well as important aspects of the text procedures,
including tests on extracts, and tests by direct and indirect contact. Part 2 explains
animal welfare requirements, and Part 3 presents the guidelines for specific test
procedures or other testing-related issues. The FDA follows ISO guidelines in some
areas, but the test procedures and requirements slightly vary between the two.

All non-clinical laboratory studies, including in vitro and in vivo studies on

biomedical materials and implants, should comply with the Good Laboratory
Practice (GLP) regulations.

Understanding of the regulatory compliance and documentation of the research in

the exploratory phase as per the industry requirements, generally assists in licensing
the technology to established companies more easily. The commercialisation of
medical devices involves appealing, not just to individual consumers but to a compli-
cated landscape of stakeholders, from doctors and patients to regulators and insurers,
all of whom have a say in whether a new technology is adopted. At the Sree Chitra
Tirunal Institute of Medical Science and Technology, Thiruvananthapuram, a cardiac
surgeon has led a large team of researchers in developing artificial heart valves a few
decades ago, which were further commercialised in the Indian market by the TTK
Healthcare group. Since then, some attempts are being made for commercialisation
of products, but not to a significant extent.
For the translation of biomedical research, innovative technologies need to be
taken from academic institutes to the market and then to hospitals and clinics for
affordable healthcare. For this, the technology first needs to be developed and eval-
uated by academia in collaboration with clinicians. Then, Indian patent and patents
under Patent Cooperation Treaty (PCT), can be filed at host institutes and this patented
technology would be transferred to the start-ups or micro, small, and mediumscale
enterprises (MSME). The technology, when matured to a higher Technology Readi-
ness Level (TRL), can be licensed to the industries (Fig. 5.7). With the help of
industries and policy institutes, it is possible to market the products to hospitals and
clinics.
5.3 Building Translational Research for Human Healthcare 119

Innovative Research at
Intellectual Property
Academia and National
Filing at Host Institute
Labs

Startup or MSME (Micro, Small and

Medium Scale Enterprises)
Interactive-
Assess product or process
intensive
scalablity
input on Techno-
commercial viability
Established Industry to reach market

Fig. 5.7 Translation ecosystem model, showing the pathways for technology transfer from the
innovation hub

To bring biomedical technologies to market, the team of academia, clinicians,

MSMEs and Industry, has to play their individual role in a very coordinated
manner, to bring the product to market.

New products undergo several considerations for market entry; including product
scalability, breadth of application area and cost effectiveness. Typically, after the
first prototype is developed and tested, a few size variants of the product undergo
more extensive testing. Some products, like the total knee joint replacement (TKR)
system or dental implants require an armamentarium of components, tools and
devices. Sometimes instruments for facilitation of accurate positioning of implants
during surgery are also required. The translational research team therefore needs to
accelerate the design, make, test, characterise and iterate cycle (the entire product
development process), and couple this to advances in machine learning.

We need an ‘Internet of biomaterials’ to advance translational research from

laboratory to the market faster.

5.4 Nourishing Industry Collaborations, Incubators,

and Start-Ups

In the healthcare system, the challenge is to create an ecosystem that brings inno-
vations into education, society, hospitals, services, and governance, and one that is
directed towards transforming the lives of people, the poor, and rural sectors in partic-
ular. It is not sufficient to develop a technology or product, but it should be commer-
cially viable and deployed for treatment/diagnosis of the relevant population across
120 5 A Challenging Frontier and Status of National Policies

the country, in a stipulated timeframe. Technology deployment and commercialisa-

tion is an area that needs to be strengthened. Each translational research institute
should have a Technology Deployment and Commercialization Cell for deploying
the technology on the ground. It is envisaged that different research groups can work
together, along with the private sectors and stakeholders, for pursuing the identified
projects and for ensuring that not only the technology is developed, but that it is
transferred to the respective commercialisation partner, so that it can reach the target
segment of society.

In the context of implant-based treatment, high cost or limited affordability

by common people has been a major concern in many developing nations,
including India.

More so, as more than 85% of the fragmented market is dominated by imported
implants. Currently, around 1 million patients need prostheses and implants every
year, with India importing Rs 7000 crores worth of them per year. Indigenously
developed implants are likely to reduce the total treatment cost, and are thus a step
towards providing affordable healthcare.
Commercially, a robust understanding of design elements as well as commer-
cial requirements aids researchers in overcoming the challenges of bringing a new
biomaterial to the market.
Currently, industry often does not recruit sufficiently skilled personnel for devel-
oping biomedical devices for local needs. A great number of talented graduates are
employed by the medical device groups—TCS, WIPRO, Cognizant and Infosys—
for servicing their clients in the USA or Europe. An excessive emphasis on low cost
also leads to the inability of industry to pay enough to attract and to retain the right
talent. It is hardly a surprise that the domestic orthopaedic industry, has very few
PhD or postgraduate engineers, despite having an annual turnover of Rs 1500 crores.
As evolution of a technology occurs, ideally, it will attract more resources for clin-
ical testing, manufacturing, and commercialisation. There is a fine balance between
accruing adequate clinical data and getting the product into the market at the earliest.
In this case, it is essential to follow internationally accepted norms. Based on these,
one can decide on the threshold number of trial surgeries, adverse event frequency
considerations and follow-up time of patients. Alongside, market evolution occurs,
sometimes leading to new application areas and new treatment paradigms. These, in
turn, affect product development.

Another challenge is market pushback. This can result in lowering the product’s
cost, better packaging, increased projection of the presence in the market and
marketing in other countries.
5.4 Nourishing Industry Collaborations, Incubators, and Start-Ups 121

Given these changes, there is a need for industry experts to be involved at the time
of commercialisation.
In joining translational research consortia, there are challenges faced by MSMEs.
Firstly, the response time is slow, and many MSMEs do not want to take the risk
of penetrating the market alone. They prefer established industry and larger players
and facilitators like KIHT to be involved in helping them reach the market and in
assisting them with business plans. Also, in some cases, the biomedical area is not
the only area of focus, and they lack experience in commercialising products in this
area, particularly in the Indian context.

To achieve significant progress, industry should be aware that the process of

idea translation involves the crossing of three ‘valleys of death’, where the
idea, prototype and product have to undergo various challenges and risks.

From idea, to functional prototype and then to the market—there are gaps known
as ‘valleys of death’. Crossing them depends on the product type, process scalability,
economics, commercial competitiveness and many other factors (Fig. 5.8). It is inter-
esting to notice that while a deep valley can be expected at the translational stage,
such a valley is shallow but wider at the commercial stage.
Some of the emerging challenges faced by the Indian biomaterials community
include inadequate linkages among academia, research and industry, ageing of the
institutional framework, weak innovation ecosystem to convert ideas into the research
programs/useful products and processes. Poor coupling among several key aspects
needs to be addressed. They are technology, trade, and social development needs,
low base of full-time equivalent scientists per million population and science and

Innovation Translation Commercialization

Lab-scale development,
Pre-clinical testing

Process scale up,

Regulatory approval and
GLP-compliant testing, GMP-regulated manufacturing
Clinical trials
National Labs,
Academia and Regulatory Agency,
Hospitals,
National Labs Industry
MSMEs

Fig. 5.8 Schematic illustration of the ‘valleys of death’ involved in the translational research on
biomaterials and implants
122 5 A Challenging Frontier and Status of National Policies

technology manpower base. A balance between basic research and well-directed

and focused research has to be maintained. India should have allocated manpower
to enhance the interfacing among clinicians, industry and academia for translation
of healthcare products and for fostering these linkages and facilitating technology
transfers. Such staff would help to drive the translational projects and to assist in
procuring funding for projects. Also, more start-ups supported by venture capital
would be able to introduce new products at competitive prices and to create new job
opportunities in the Indian context. The sequence of chronological growth stages for
a start-up or an incubatee is shown in Fig. 5.9.

While a start-up may have technologically smart founders, and it is relatively

easy to take the invention from idea to validation stage, more difficulties would
be faced as one progreses towards the scale up stage.

•Idea formulation
•Idea validation
Idea •Prototype
Validation •Minimum viable product

•Early revenue
•Self funding
Seed •Funds from family and friends
Funding •Angel Investment

•Early traction
•Loyal customer base
Growth •Rounds of Venture Capitalist funding
Stage

•Repeatable user acquisition process

•New Growth Channels
Scale up •Rounds of Venture Capitalist funding
Stage •Exit, initial public offering, Merger and Acquisition

Fig. 5.9 The various chronological stages of start-up growth (Source National Report on
Government of India’s States’ startup ranking 2018—www.startupindia.gov.in)
5.5 Addressing the Gaps in Medical Education and the Clinical Research Ecosystem 123

5.5 Addressing the Gaps in Medical Education

and the Clinical Research Ecosystem
5.5.1 Education and Training

To accelerate indigenous implant development, the involvement of clinician scientists

should be emphasised. Pre-clinically studied biocompatible implants or devices need
to undergo clinical trials in human patients. Apart from the human ethics committee
approval, clinical studies require strict regulatory approval and funding to support
them. Once a device is proven to provide clinically appropriate patient outcomes,
the technology for device manufacturing can be transferred to biomedical device
companies. The involvement of clinicians at the ideation stage and the clinical trial
stage is therefore extremely significant.

The translational ecosystem in India significantly lacks the involvement of

clinician researchers and this is a challenge of the first order.

In India, intermittent efforts were invested to streamline and to support the medical
education system. The guidelines or recommendations of the various expert commit-
tees were included in the report on Medical Education and Support Manpower
(1975), Indian Council for Social Science Research – Indian Council for Medical
Research (ICSSR–ICMR) (1981), National Health Policy (1983), the Medical Educa-
tion Review Committee (1983), National Policy on Education (1986), the Expert
Committee on Health Manpower Planning, Production and Management (1987) and
more recently, Niti Aayog (2015).

The current medical curriculum places little emphasis on research or

bioengineering-focused projects, both at the undergraduate and postgraduate
levels.

Currently, Phase I of the medical curriculum includes preclinical subjects

of anatomy, human physiology and biochemistry (15 months). Phase II covers
pathology, microbiology, pharmacology, forensic medicine and community medicine
(18 months). Phase III covers medicine and surgery, including orthopaedics, obstet-
rics and gynaecology, paediatrics and eye and ENT medicine. Clinical postings begin
in Phase II, and Phase III includes a community medical posting. After passing the
MBBS, candidates are granted provisional registration for one year, during which
they undergo a compulsory rotating internship, which includes hospital training and
community health work.
Also, science-based subjects, like cell and molecular biology, including
microscopy-based analysis, biostatistics and fundamentals of biomedical engineering
must be taught in the undergraduate medical curriculum.
124 5 A Challenging Frontier and Status of National Policies

An immediate aim should be to build a vibrant education and research ecosystem

in existing AIIMS and other national medical institutions. To achieve this, a bioengi-
neering immersion programme (internship programme) should be offered to under-
graduate medicine students and clinical immersion program should be offered to the
graduate students in bioengineering.

An MD/PhD program needs to be introduced for clinicians and also important

would be an external registration PhD program for biodesign innovators in
academic institutions.

5.5.2 Clinical Research Ecosystem Development

The existing ecosystem is lacking in opportunities for clinicians to pursue research

work, and medical colleges are regularly promoting faculty without a track record
of mentoring researchers or doing research. Promotions require that faculty should
have at least one or a few publications, but the Medical Council of India (MCI)
does not specify the level of authorship required. The medical system is significantly
affected by the time that is given to government practice versus private practice.
Often, clinicians are not very well paid at government institutions, the facilities are
not adequate and the patient load is very high.
In such a situation, it is understandable as to why the motivation for clinicians
to spend time on research is low, and this is a challenge for addressing unmet clin-
ical needs through research innovation in medical institutions. Also, the number of
research collaborations and the number of multicentric clinical trials are on the lower
side in India.

For many clinical studies involving new implants, the recruited patients often
do not adhere to the follow-up required, and therefore the clinician researchers
are unable to monitor the progress of the clinical trial outcome.

Other factors which are affecting the ability to do good quality research are the
poor quality of writing of case files and hospital records. Good quality medical
records are required for research, particularly for retrospective research. Also, many
medical colleges do not employ medical statisticians. Other bottlenecks include lack
of animal facilities in many newer medical colleges and lack of funding for research.
The National Medical Commission Bill was introduced by the Minister of Health
and Family Welfare on 22 July 2019. The bill seeks to repeal the Indian Medical
Council Act, 1956, and provide for ‘a medical education system which ensures
availability of adequate and high-quality medical professionals, adoption of the latest
5.5 Addressing the Gaps in Medical Education and the Clinical Research Ecosystem 125

medical research by medical professionals, periodic assessment of medical institu-

tions, and an effective grievance redressal mechanism’. With political will to provide
health for all, it is hoped that the current status of medical education will be revamped,
so that the clinicians are better prepared for the twenty-first century.

5.6 Harnessing the Benefits of Biomaterials for the Country

The federal government funded multi-institutional research programmes, involving

clinicians and entrepreneurs, are to be pursued with an endpoint objective of manu-
facturing cost-effective patient-specific implants and devices for targeted biomedical
applications. Such programmes should involve careful assessment of technology
and manufacturing readiness levels (TRL and MRL). New national laboratories
and research institutes should be dedicated to address the clinically relevant prob-
lems in human diseases. To develop biomedical device prototypes, multi-institutional
research programmes must involve clinical immersion and translational feasibility.
Examples of national institutes involved in multi-institutional research programmes
are Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST),
Thiruvananthapuram, and the Translational Health Science and Technology Institute
(THSTI), Faridabad.

In the university campus, the research ecosystem must include medical

hospitals for meaningful collaboration with active clinicians.

Such an ecosystem would facilitate human resource development via more inter-
disciplinary academic programmes with a strong curriculum, involving engineering
design, manufacturing, biomaterials, biology, and data sciences.
Worldwide, the idea of patient-specific implants for musculoskeletal reconstruc-
tion is rapidly gaining acceptance among surgeons. The patient-specificity should
also carefully consider the bone condition of the subject, in case of implants for
musculoskeletal applications. This also changes the way in which surgeons plan and
execute their surgeries. However, this paradigm has not been introduced in clinics in
India to a large extent, yet.
The need for indigenous cost-effective novel dental implants with better biome-
chanical stability to secure the increasing oral health rehabilitation requirements, is
expected to increase in the next 10 years, as the country is shifting towards having a
higher proportion of elderly population. Abutment loosening is of great concern
currently in dentistry, which often necessitates additional post-operative surg-
eries (see Fig. 5.10). This demands thoughtful design of abutment–screw interface
geometry along with a rugged interlocking design to connect the components.
126 5 A Challenging Frontier and Status of National Policies

Fig. 5.10 Clinical challenges in human patients due to edentulism which requires partial/full dental
restoration using implants

Patient-specific implants have shown better performance over their generic

counterparts worldwide in clinics due to the precise adaptation to the region
of surgery, reduced procedural times, better aesthetics and most importantly
greater integration with the injury site.

It is proposed to start a national consortium, to accelerate the translation of

innovative research on biomaterials science and biomedical engineering towards
commercialisation of clinically validated solutions.

The national mission is to be envisioned and promulgated with leading

researchers from IISc/IITs/NITs/National laboratories/industry to facilitate
end-to-end total integration of manufacturing lifecycle of biomedical implants.

The mission of such a consortium would be to enable acceleration of indigenous

innovation with respect to high-performance biomaterials, manufacturing/testing,
materials processing technologies and biomedical devices through cross-disciplinary
translational mission-mode efforts among academia, national laboratories and
industries, with intensive-interactive inputs from clinicians and policy institutes.
The Government of India has shown commitment to support several technolog-
ical missions. There are nine technology missions of the Office of the Principal
Scientific Adviser to the Government of India. These missions are to be imple-
mented by the Prime Minister’s Science, Technology and Innovation Advisory
5.6 Harnessing the Benefits of Biomaterials for the Country 127

Council (PM-STIAC) Missions, in the areas of Natural Language Translation, Elec-

tric Vehicles, Artificial Intelligence, National Biodiversity Mission, Quantum Fron-
tier, BioScience for Human Health, Waste to Wealth, Deep Ocean Exploration and
Accelerating Growth of New India’s Innovations (AGNIi). AGNIi provides a plat-
form for innovators to scale up their market ready products by creating pathways for
licensing, technology transfer and market access. This can provide an opportunity
for commercialisation of indigenous biomedical implants and devices.
A challenge that is expected with respect to the uptake of indigenous implants is
the mindset that indigenous implants are not reliable. Even if the indigenous implants
have comparable technical specifications to the imported ones, one can expect this
mindset to be widespread.

The already-perceived notion in patients, that indigenous implants are not

reliable, is to be addressed by the key opinion leaders from the medical
community.

5.7 Closure

To sum up, it is essential to bring together engineers, scientists (biologists, partic-

ularly), clinicians, and industry for the development of biomaterials and implants.
Many of the challenges, emphasised in this chapter (see Fig. 5.11), demand the estab-
lishment of more medtech zones with vibrant translational ecosystems in different
strategic locations in India, to take the laboratory-scale innovations to market. In the
next chapter, I will discuss a detailed road-map of my recommendations.

Accelerating Building translational Addressing gaps in medical

Regulatory research for human education and the clinical
Approval health research ecosystem

Challenges in the Biomaterials and Bioengineering Ecosystem

Nourishing industry Harnessing the benefits

Strengthening
collaborations and of biomaterials for the
basic research
start-ups country

Fig. 5.11 Summary of challenges in the biomaterials and bioengineering ecosystem

Chapter 6
Recommendations

Implement national regulatory framework to

streamline accelerated regulatory approval processes

Strengthen basic research in biomaterials sciences for

accelerated innovation of next generation biomaterials

Build up clinical, context-driven, translational research

toward treatment of human diseases

Nourish industry collaborations and capabilities,

grow and sustain incubators and start-ups

Revamp medical education and clinical research

ecosystem, to train and collaborate with clinicians

Introduce and implement national policies and action

plans to harness benefits of biomaterials for the public

Abstract The sixfold recommendations presented here can accelerate the develop-
ment of indigenous high-quality biomedical materials and implants and contribute to
making the treatment of millions of patients in India affordable. On its 73rd year of
independence, India is surging ahead. Right at the heart of global geopolitics, it is one
of the world’s best-performing human resource capitals, an emerging economy, and
a software giant. Nevertheless, what about the scientific wealth of the nation? For any
country that aspires to achieve faster, more sustainable and inclusive growth, science
and technology need to emerge as key drivers of socio-economic development—
especially so that it can cater to the healthcare needs of 1.3 billion citizens. For that,
the nation needs to exploit unique innovation opportunities for its large and talented
pool of scientists, engineers, clinicians, innovators, and start-up entrepreneurs, for
achieving the dream of a ‘healthy’ India. Although the biomaterials community of
India is increasingly visible for its scientific outputs and research publications, we
© Springer Nature Singapore Pte Ltd. 2020 129
B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0_6
130 6 Recommendations

are still struggling to execute translational research, to bridge the gap between basic
and clinical research and to take laboratory scale research to the patient’s bedside. In
terms of translational activities in healthcare sector, significant efforts are invested for
the biomedical diagnostic and extracorporeal devices, with much less visible efforts
on biomaterials, implants, and tissue-engineered scaffolds.
For affordable healthcare diagnostics, the nanotechnology-based skill set, micro-
fabrication capabilities, and related engineering capabilities, are particularly explored
in the Indian context. Against the above perspective, it is expected that the recom-
mendations laid down in this chapter will usher a new era in the field of biomaterials
science, leading to significant translational research on implants. Many of the recom-
mendations will be equally applicable in many of the developing nations around the
world. It is emphasised that the translational research on implants demands stringent
adherence to strict regulatory protocol. Summaries of relevant conferences, work-
shops and road-mapping meetings that contributed to the recommendations presented
here are given in Appendices D and E, respectively.

6.1 The Translational Gap

The sustained growth of biomaterials sciences and biomedical engineering would

certainly require intense translational research, to enable commercialisation of new
implants and devices for the benefit of human healthcare. Thus, it is important to
inculcate a culture of innovation in our academic universities and medical institutions,
with the active support of all science and technology departments of the Government
of India, state governments, and the corporate sector—to fill the existing translational
gap. Various research groups across the country have to work towards coordinated,
innovation-led efforts essential for scientific innovations to impact society, within
reasonable timelines.

6.1.1 Science at the Local

Dramatic advances have taken place in India in the fields of biomaterials, tissue
engineering, drug delivery systems, cellular engineering, and biomedical devices in
recent years. Technological innovations in diverse spheres of science are driving
growth: from biodegradable implants, internal fixation devices, patient-specific
musculoskeletal implants to real-time sensor embedded implants. It is imperative that
indigenous design, development, and manufacturing capabilities should synchronise
well with translation of research knowledge into clinical practice.
6.1 The Translational Gap 131

6.1.2 Regulatory Impasse

A key bottleneck in the medical devices industry is the country’s skewed regulatory
paradigm. Let us ask why Indian-manufactured medical devices still suffer from the
perception worldwide that they are low-cost and poor quality?

The absence of well-formulated and effective regulatory mechanisms is

responsible for not bringing Indian endeavours its due for performance or
innovation.

While an indigenous industry has been present since the 1970s, the first attempt at
regulation came about in 2006—that too, by an inappropriate notification that clubbed
medical devices with drugs. The mismatch resulted in medical devices coming under
the drugs regulatory body, CDSCO, with glaring loopholes that ignored the fact
that devices are different from drugs and that pharmaceutical professionals cannot
effectively regulate the medical devices industry.
In the last one decade, innumerable representations from industry to correct this
wrong have been ignored. It is, therefore, not surprising that the large majority of
Indian clinicians and health professionals continue to place their faith in ‘imported’
devices. As a result, imports continue to dominate, accounting for 75–95% of the
Indian medical device market.

A new and effective regulatory framework for biomaterials and implants is the
need of the hour.

In order to move in the right direction, the government is planning to set

up a Medical Devices Authority (MDA) for the entire spectrum in the medical
devices sector, including implants. The MDA will be separate from the Central Drugs
Control Standard Organization (CDSCO), and will not have any role in pricing,
which will be overseen by the National Pharmaceutical Pricing Authority (NPPA).
The body would comprise representatives from industry, policy makers, and active
medical practitioners.
132 6 Recommendations

6.1.3 Steering Science and Technology

The recommendations made in this chapter are expected to align with the Government
of India’s new strategic initiative, the National Science, Technology & Innovation
Foundation (NSTIF). This body was established to steer the management of science
and technology in the country, including science education, scientific innovation,
coordination, monitoring, and guiding implementations in various sectors. In inter-
disciplinary research programmes, young researchers from a host of disconnected
disciplines—engineering to pharmaceutical sciences—have an opportunity, along
with the responsibility to take on the mantle of leadership.

6.2 Priority Recommendations for Fostering Innovation

and Growth of Biomedical Materials and Implants

For ambitious nation-building, six key recommendations are long overdue. Policy is
at the heart of the journey towards change. I propose a road map to pinpoint directions
necessary to navigate the terrain ahead.

6.2.1 Implement National Regulatory Framework

to Streamline Accelerated Regulatory Approval
Processes

The following recommendations are suggested to be strongly considered by the

Medical Devices Technical Advisory Group (MDTAG), constituted by Ministry of
Health & Family Welfare, Government of India, to advise Central Drugs Standard
Control Organization (CDSCO) in July, 2019. It is felt that MDTAG should have more
representatives from academia (active bioengineering researchers) and industry. Key
recommendations are outlined in Fig. 6.1.
First Three Years (3)

1. Develop and enforce a medical device-specific national regulatory framework,

to take into account globally validated standards provided by the International
Medical Device Regulators Forum (https://www.imdrf.org/index.asp). Such a
framework must recognise that implants and medical devices typically feature
a wide variety of technologies, involving the material sciences, engineering,
electronics, and other disciplines.
 Implement National regulatory framework to streamline accelerated regulatory
approval processes

Formulate and implement National regulatory framework and

policies for biomedical implants and biomaterials
Reformulate protocols related to Randomized Controlled Trials
Accelerated regulatory approval for indigenous implants
Establish national registries on legislation of implants
Regulation of company, start-ups and incubators

9
6.2 Priority Recommendations for Fostering Innovation …

1 2 3 4 5 6 7 8 10 Years

National regulatory organisation

Post-market surveillance system
Transition time for regulatory organisation and industry

Fig. 6.1 Summary of important recommendations to develop a national regulatory framework

133
134 6 Recommendations

It is inappropriate to club medical devices and drugs into the same

regulatory mechanisms and processes.

2. Develop a strong knowledge base on regulatory matters, with accessible regu-

latory officials who can advise on regulatory requirements during the product
development stage. It is important to train students at the PhD level on regula-
tory requirements. Regulatory agencies should have a sense of duty to engage in
dialogue regarding how regulations should emphasise their interests in protecting
patients, while facilitating promising biomedical technologies.
3. Formulate an accelerated pathway for regulatory approval involving experts that
can be approached to discuss the regulatory requirements at any point in the
research and development process, in particular for clinical trials. It is recom-
mended that agencies should be formed to help facilitate and organise clinical
trials, in line with regulatory requirements. Also, it is recommended to simplify
procedures to seek patient consent prior to clinical trials and ethical approvals
for animal studies.
4. Reformulate the rules and regulations associated with randomised controlled
trials (RCT), which are currently very restrictive, in consultation with medical
institutions. This will significantly facilitate the clinical translational research on
biomaterials and implants, in additon to maintaining an online database.
5. Build facilities and capabilities for effective regulation of medical devices
through the creation of a regulatory organisation comprising of qualified
professionals in the appropriate disciplines.
6. Establish national registries enabling legislation on medical devices, under
national regulatory framework. Policies should regulate the use of medical
devices to improve healthcare outcomes and the availability of high-quality
medical devices.
7. Registration of company and product should be made mandatory, based on regu-
latory clearance from the national regulatory agency, similar to that applicable
to international products being marketed after clearance from USA-based FDA
or European CE.

First Five Years (5)

1. It is imperative that India has a well-established national regulatory organisation
for biomaterials, implants, and biomedical devices by 2025. This organisation
should act independently as a nodal centre to enforce quality and appropriate
regulation on all the indigenous development and the use of imported implants
or biomedical devices in India.
2. Account for and announce a transition time for both the regulatory organisation
and industry. After completion of the announced transition time, ensure rigorous
and absolute implementation of regulatory requirements to uproot all devices of
inappropriate quality and organisations producing such devices from the market
place.
6.2 Priority Recommendations for Fostering Innovation … 135

3. Develop and enforce post-market surveillance systems (PMSS), to monitor

product safety after the products are implanted or deployed.

6.2.2 Strengthen Basic Research in Biomaterials Sciences

for Accelerated Innovation of Next-Generation
Biomaterials

It is widely perceived that better understanding of the ‘science’ aspect of biomaterials

development would lead to better implants and scaffolds for biomedical applications.
Key recommendations are outlined in Fig. 6.2.
First Three Years (3)

1. Computational data science-based approaches, like machine learning algorithms,

should be employed to accelerate the development of ‘ideal’ bone-mimicking
material, which remained a dream for generations of biomaterials scientists. In
such an approach, fine scale structural data of various (multi)-ion-doped CaP
bioceramics as test data and the structural analysis of natural bone as training
data can be used.

It is recommended to effectively adapt artificial intelligence (AI)

approaches and/or machine learning (ML) algorithms for better
predictability of clinical performance of biomaterials/implants.

2. Taking forward significant interest in 3D and 4D Bioprinting in the next few

years, an exciting recommendation would be to formulate and implement
‘Space Bioengineering’ as a flagship national programme, in line with ISRO’s
human spaceflight programme. Such a programme would enable biofabrication
of programmable self-assembly of 3D tissue and organs constructs in micro-
gravity culture conditions. This requires rational design and manufacturing of
3D bioprinters with significant on-ground testing and evaluation of spacewor-
thiness. The scientist can plan to conduct on-ground experiments to use 3D
bioprinting to develop scaffolds with spatio-temporal control of molecular and
physical signalling for the newly regenerated tissues to mature, to whole organs
for transplantation.

Once successful, this will place India as the only fifth nation to launch such
an ambitious space bioengineering program.

3. Synthetic biopolymers and natural soft biomaterials are by far the most widely
investigated in India and globally. However, structure–property correlation of soft
 136

Strategies to strengthen basic research for accelerated innovation of next

generation biomaterials

AI/ML approaches for accelerated biomaterials development

Structure-property correlation of biomaterials (high resolution multiscale measurements)
3D Bioprinting in microgravity for human space flight program
Co-culture and lab-on-chip approach for cytocompatibility evaluation
Cell signalling pathway in cytocompatibility assessment AI: Artificial Intelligence
3D Bioprinting of cartilage ML: Machine learning
Computational modeling of hierarchical interactions of biomaterials with living systems

1 2 3 4 5 6 7 8 9 10 Years

Pre-clinical/clinical translational research on biomedical Strategic Innovation centres on Biomaterials and

devices, based on biophysical stimulation Biomedical Implants
Quantitative exploration & curation of biomaterial 3D tissue manufacture and biomechanics evaluation
informatics suite

Fig. 6.2 Summary of the major recommendations to strengthen basic research in biomaterials science
6 Recommendations
6.2 Priority Recommendations for Fostering Innovation … 137

materials remain largely unexplored. It is recommended to explore the funda-

mental understanding of macromolecular structure/viscoelastic property correla-
tion of polymeric biomaterials using a diffusive wave spectroscopy (DWS)-based
micro-rheology approach, together with small angle X-ray scattering (SAXS).
Such combinatorial analysis allows one to probe into the origin of the viscoelastic
property variation in terms of structural changes due to the complex interactions
among macromolecules.
4. The structure–property correlation of many of the implantable bioceramics is not
well established. It is recommended to use a synchrotron facility, i.e., extended X-
ray absorption spectroscopy (EXAFS), to record high resolution data for compo-
sitionally tailored CaP-based bioceramics, one of the widely investigated inor-
ganic biomaterials. This, together with computational techniques, like molecular
dynamics simulation, density functional theory (DFT), can be used to precisely
determine the dopant distribution in energetically stable crystal structures of
doped CaP biomaterials.
5. Regarding cytocompatibility evaluation, the first recommendation would be to
co-culture endothelial cells with target tissue-specific cells, as such an approach
facilitates better maturation of engineered tissues by enhanced capillary forma-
tion in extended timescale. The second recommendation would be to adopt the
lab-on-chip approach, wherein in vitro experiments are carried out in designed
biomicrofluidic devices under physiologically relevant shear.
6. It is also recommended that researchers develop an in-depth understanding of the
cell signalling pathways involved in cell functionality changes for implantable
biomaterials. For advanced biomaterials-based nanotechnologies, cellular and
tissue therapeutics should be focused on the fine tuning of cellular behaviour.
Also, there should be development in advanced delivery systems for drugs,
proteins, peptide-based products, and gene therapeutics. This requires extensive
collaboration with biologists.
7. With reference to 3D printing, it is recommended to formulate a universal binder
to print a wide spectrum of implantable biomaterials, as well as to develop
insightful understanding of the binder-material interactions, preferably using
synchrotron studies.

Currently, most of the commercial 3D printers can be used to print standard

materials using the company’s patented binder.

This severely restricts research on 3D printing of patient-specific implants using

new biomaterials and material-specific binder.
8. With respect to cartilage tissue engineering, a biomaterial, acting as a cell
carrier for cartilage repair, should serve as a temporary biodegradable scaffold
that permits synthesis of extracellular matrix from delivered cells, while leading
to a close fit attachment to the perimeter of the cartilage defect. Super macro-
porous (0.1–100 µm) polymeric gels can offer great potential as scaffolds for
138 6 Recommendations

cartilage tissue. An in situ gelling system can help to overcome the problem of
having a good fit of the scaffold to the perimeter of the cartilage defect (less inva-
sive delivery form). Chondrocytes need to be maintained in the rounded hyaline
form (with suitable growth factors).
9. With respect to optimisation of a material and therapy for bone tissue engi-
neering, laser/electric field stimulation can guide mesenchymal cells towards
osteogenesis, contributing to bone growth. Synergistic interaction among the
electric/magnetic field stimulation and biomaterial substrate properties can guide
stem cell differentiation through different lineages. The outcome of such research
programmes will have significant relevance for the emerging field of Bioelec-
tronic Medicine. Another approach could be to examine the efficiency of highly
intense laser sources in order to establish a dynamic poling of electroconductive
composites, and subsequently study osteogenesis on such laser-treated surfaces.

First Five Years (5)

1. Similar to cell culture experiments, the antibacterial properties of biomaterials are
mostly evaluated using a single pathogenic strain type (S. aureus, S. epidermidis,
E. coli, etc.). The competition involved in interactions among prokaryotes and
eukaryotes are much less explored in the biomaterials community and cannot be
assessed by studying their respective interactions with biomaterials, in isolation.
The recommendation would be to explore this aspect, prior to pre-clinical study.
2. In the context of electric field stimulation of cells on biomaterials, it is recom-
mended to adopt quantitative modelling approaches, using molecular dynamics
(MD) and first principle calculations. Deeper knowledge in this area would
help to develop biophysical stimulation devices for regenerative engineering
applications.
3. The bench-to-bed translation of the concept of ‘electrical field stimulation of
stem cell niche’ in the context of tissue engineering and regenerative medicine is
another aspect that needs further investigation. Although a multitude of in vitro
studies are being reported in literature, translational research would require
more pre-clinical studies, with microelectronic miniaturised modules to deliver
electrical stimulation, followed by thoughtful clinical trials.
4. It is recommended to establish a mathematically rigorous cross-disciplinary
framework that will allow a systematic quantitative exploration and curation
of critical biomaterials informatics to objectively drive the innovation efforts
within a suitable uncertainty quantification framework. Additionally, one needs
to consider multiple physics-based approaches and potential coupling between
them in extracting this core knowledge (e.g., multifunctional properties needed
for biomedical applications). This will enable a rigorous foundational framework
that allows objective extraction and fusion of the incomplete and uncertain mate-
rials knowledge, to address the central impediment in streamlining and enhancing
the efficacy of current biomaterials innovation efforts.
6.2 Priority Recommendations for Fostering Innovation … 139

First Ten Years (10)

1. What is needed in the next one decade is to develop strategic innovation
centres to support the faster development of biomedical devices, which are
to be guided by an extensive network of research groups across bioengi-
neering/materials science/mechanical engineering/biological sciences/chemical
sciences/computational data sciences in academic universities, medical insti-
tutions, and national laboratories. These centres should facilitate long-term
strategic research programmes involving basic scientists, doctoral students, and
post-doctoral staff, regulatory consultants, for designing and prototyping of
biomaterials-based medical devices. Another recommendation would to estab-
lish biomedical device testing facilities in those strategic innovation centres, as
mentioned above. Currently, good materials testing and characterisation facilities
are available in major academic institutions.

High-throughput manufacturing and accelerated biocompatibility testing

should be the focus of these futuristic strategic innovation centres.

2. More multidisciplinary research efforts in the area of 3D (Bio) printing are to be

invested, involving analysis of complex anatomical features, clinical imaging (CT
or MRI scans) algorithm and printer development. Specific attention is to be paid
to optimisation of bioink rheology printing parameters, gelation kinetics, struc-
tural and mechanical stability, and biodegradation of soft polymeric hydrogels.
Printing of a variety of materials should be possible with high spatial control and
resolution, through multiple printing heads (co-axial extrusion) using different
techniques such as heated, non-heated, pressure-assisted, and extrusion combined
with a laser unit for direct polymerisation. Further applications to be pursued are
drug development and toxicity analysis, scaffold-based tissue engineering, auto-
mated tissue-based in vitro assays for clinical diagnostics, and modular tissue
assembly.
3. It is recommended to build a 3D tissue manufacture and biomechanics evaluation
suite. The suite should allow high-throughput culture of a variety of tissue and
acellular products, such as heart valve tissue, blood vessels, ligament/tendon
bone, and cartilage. It should also allow testing of acellular biomaterials, such as
hydrogels, polymers, elastomers (rubbers), ceramics, metals, composites, etc.

6.2.3 Build Up Clinical, Context-Driven, Translational

Research Toward Treatment of Human Diseases

The major recommendations to build a stronger and more effective translational

research ecosystem are summarised in Fig. 6.3.
 140

Fig. 6.3 Recommendations for enhancing translational research ecosystem on biomaterials and implants
6 Recommendations
6.2 Priority Recommendations for Fostering Innovation … 141

First Three Years (3)

1. It is recommended to launch strategic research programmes on the most prevalent
human diseases. The national societies like Society for Biomaterials and Artificial
Organs (SBAOI) or Biomedical Engineering Society of India (BMESI) or Society
for Tissue Engineering and Regenerative Medicine India (STERMI) together
with National Academy of Medical Sciences (NAMS) are suggested to conduct
critical analysis of clinical cases registered across hospitals/clinics to arrive at
the ranking of the most prevalent human diseases. The funding agencies can call
for proposals on a priority basis to address the unmet clinical challenges.
2. In the context of biocompatibility testing, the researchers mostly report the cyto-
compatibility results, analysed using a host of complementary molecular biology
assays. It is equally important to assess the genotoxicity of the nanobiomate-
rials in a size- and dose-dependent manner, using comet assay, single-cell gel
electrophoresis or micronucleus (flow cytometry) techniques. The quantitative
analysis, together with the mechanism of DNA fragmentation, has large signifi-
cance for epigenetic changes. This obviates the necessity of evaluating genotoxic,
epigenetic, and carcinogenic effects, to improve the clinical acceptability of the
material.
3. It is recommended that the researchers invest future efforts to explore the
host response modulation of immunomodulatory scaffolds (acellular or decellu-
larised), using the concept of regenerative immunology (phenotypic plasticity of
immune cells, or by targeted co-delivery of immune cells with the organ-specific
functional cells).

Immuno-modulation should emerge as a therapeutic discipline which

can cater to the needs of transplantation, transfusion medicine, tissue
engineering, regenerative medicine, and implantation.

4. Another important recommendation is that vascularisation phenomena require

significant attention of the researchers pursuing tissue engineering and regener-
ative medicine.
5. In the context of 3D bioprinting, it is recommended to focus first on develop-
ment of in vitro disease models, which could be used by Indian pharmaceutical
companies for in vitro drug screening.
6. Establish more GLP-compliant research facilities, such as those at CSIR-IITR
and SCTIMST, at strategic innovation centres. It is recommended to follow
the International Organization of Standardization (ISO) protocols for evaluating
biocompatibility of biomaterials or devices using animal and human cell cultures.
7. Another equally important recommendation is to establish GMP-compliant
manufacturing facilities, in strategic innovation centres for translating research
outcomes to marketable implants/devices. Specific standards for safety, Quality
Assurance (QA)/ Quality Control (QC), and ethical norms need to be enforced
in all these facilities.
142 6 Recommendations

8. Knowledge transfer and training of a well-trained human workforce with multi-

disciplinary capability for creating an innovation ecosystem. The workforce
for tomorrow must be exposed to the diverse multidisciplinary knowledge of
medicine, biology, chemistry, materials science, engineering/manufacturing, etc.
This would allow them to collaborate across the silos, where researchers often
confine themselves to traditional knowledge domains.

First Five Years (5)

1. The scaling of the existing translational programmes with more effective
interfacing among clinicians, engineers, and biologists is recommended. The
emphasis should be on developing cost-effective healthcare solutions of high
quality. One example of a recently opened centre is the ‘Centre for Engineering
in Medicine’ at IIT Kanpur, which will offer Masters and PhD level courses.
2. Establish large animal facility to cater to significant pre-clinical biocompatibility
study of the biomaterials. Currently, Indian Veterinary Research Institute (IVRI),
with which is headquarter at Izatnagar, UP, has five campuses at different loca-
tions in the country, namely Pune, Kolkata, Palampur, Mukteswar, and Bengaluru.
Many of these institutes have large animal facilities primarily to cater to investi-
gate prevalent animal diseases for better healthcare of the animals as well as for
drug/vaccine development.

India should have more specialised institutes for pre-clinical testing of

implants in large animals under the broad umbrella of IVRI.

3. In the field of whole functional organ tissue engineering, it is recommended

to pursue research on cartilage, bone, bladder, trachea, heart valve, heart, lung,
nerve, skin and kidney, besides whole tissue reconstruction. Of note, technolo-
gies for connective and skeletal tissue like critical bone defects, wound care
management, and vascular grafts are already maturing in India.
4. It is advised to develop biomaterial and biomedical research programmes, which
can be funded by the ministry of health or the ministry of science and technology
of regional states in India. After these state-level centres demonstrate satisfactory
progress, those units may be enabled to evolve into full-fledged national research
institutes.

First Ten Years (10)

1. A long-term recommendation would be to establish a vibrant translational
research ecosystem, comprising of a group of institutions of eminence as
members of a consortium, which transfer technologies at TRL 4–5 level to an
industrial partner (start-ups, MSME, or larger industrial partner). This should
essentially be followed to establish SCTIMST/THSTI–like translational research
institutes in the area of biomaterials and implants. It is important to establish
6.2 Priority Recommendations for Fostering Innovation … 143

newer translational research institutes that should have R & D facilities that can
be utilised for large animal studies on biomedical implants and devices.

The new translational institutes should facilitate multi-centric clinical trials

on pre-clinically proven implants and biomaterials.

2. The majority of indigenous biomedical devices/implants should have a ‘Make-

in-India’ label by 2030.

6.2.4 Nourish Industry Collaborations and Capabilities,

Grow and Sustain Incubators and Start-Ups

One of the important lacunae in the entire ecosystem is the lack of strong presence
of indigenous industry to complete the cycle of ‘science-to-product’ innovation. To
this end, the major recommendations are outlined in Fig. 6.4, and more details are
given below.
First Three Years (3)
1. Establish strategic policy centres to conduct market research on biomaterials and
implants. The dynamic changes in implant market should be carefully studied,
and the market research results should be accessible to industries, MSMEs, and
start-ups.
2. Strengthen and expand KIHT/AMTZ–like ecosystems across different strategic
locations in India to create strategic innovation centres to facilitate transfer of
clinically validated technologies from academia/national laboratories to estab-
lished industry. Such centres should develop the capability for commercial-
scale production of biomedical-grade materials such as hydroxyapatite
powders/blocks/granules, Ti6Al4V/stainless steel/CoCrMo blanks, UHMWPE
blocks, and biodegradable polymers (PLA, PLGA, etc.).

The unavailability of biomedical grade powders or solid blanks for

proof-of-concept studies often restricts research in academia and national
laboratories.

3. KIHT/AMTZ group of institutions should maintain a national registry of medtech

innovations from across the country. This should be made available to companies,
which can then analyse the commercialisation potential of the innovations and
take the promising ones to market.
4. The healthcare sector should have significant investment from the government
for manufacturing of biomedical materials/implants, and for an appropriate regu-
latory framework for the sector; it thereby should minimise the import of substan-
dard or even recalled devices. Competitive cost-structure analysis of newly
 144

Nourish industry collaborations and capabilities, grow and sustain incubators

and start-ups

Establish strategic policy centres for market research

National registry of medtech innovations
Pilot scale production of biomedical grade
HA/Ti6Al4V/CoCrMo/UHMWPE/PCL/PDMS, etc.
Mandatory involvement of MSME/company in large translational
research programs and institutes
Valuation of IP as intangible asset for startup valuation
Mandatory management training of entrepreneurs

1 2 3 4 5 6 7 8 9 10 Years

Strengthen innovation ecosystem in startups, MSMEs, industry

Implement industry 4.0 in biomedical manufacturing sector
Enable MSMEs to form viable contract manufacturing
Establish research parks at selected NITs/IoEs

Fig. 6.4 Key recommendations to nurture and nourish industry collaborations

6 Recommendations
6.2 Priority Recommendations for Fostering Innovation … 145

indigenous implants and materials with respect to similar products currently

sold worldwide is warranted.
5. Promote industry-focused clinical excellence as a driver of translational research
and involve industry, right from TRL-1 stage, while conceiving translational
research programmes at strategic innovation centres. This demands commensu-
rate funding mechanisms that strongly emphasise collaborative research with at
least one mandatory industry partner with tangible incentives, to ensure impact
beyond publications.

The institution–industry teams should carry out due diligence to estab-

lish the technologies’ assets and liabilities and evaluate their commercial
potential.

6. Mandatory management training for biomedical entrepreneurs, so that they learn

about strategy, branding, product positioning, assessing risk factors, development
of business and commercialisation plans and marketing, sales and distribution
strategies of biomedical implants and devices.
7. Industry experts to participate as adjunct faculty in professional education (e.g.,
PhD programme in Biomedical Engineering) to help build a knowledge base
on market opportunities and needs and also commercialisation of products and
technologies.
8. Create incentives to attract indigenous entrepreneurs, recognise incubators as
for-profit companies, and enhance the number of start-ups (both private and
public institutional). Engage with the next generation of researchers to develop
an entrepreneurial spirit and awareness, which is very important for developing
the next generation of start-up founders.
9. An IP training certification of all innovators before receiving funding exposes
them to IP-related litigation procedures and also protocols with freedom to
operate analysis. Valuation of IP is an intangible asset for start-up valuation.

First Five Years (5)

1. Establish and strengthen the innovation ecosystem in start-ups/MSMEs/industry.
Promote more standard contract agreements between industry and academia to
accelerate engagement with single or multiple universities. It is recommended to
introduce an optional tenure of biomedical researchers in industry for 6 months
every 2–3 years in their career. Researchers from academia/national laboratories
should be allowed to act as part-time consultants for industry R&D programmes.
Without innovation, they may not be able to generate patents, and as a result
they might fail to compete with international big players. Incubators must have
specific skills to assess the commercial potential of technologies, and incubatees
should be mentored by a pool of mentors for innovation and translation.
2. Enable Indian MSMEs to form viable contract manufacturers with market pene-
trating strategies by selling products to established companies, such as Meril
146 6 Recommendations

Healthcare, Stryker, Smith and Nephew, and Zimmer. For example, the top global
orthopaedic manufacturer companies are consuming 1.5–2 million femoral heads
a year. Also, the dental market in India presents a good opportunity, since there
are not even a handful of local manufacturers yet.
3. Improve the country’s knowledge of the manufacturing process and its effects,
through courses on automation, information from sensors, data exchange (Fourth
Industrial Revolution of digitisation, i.e., Industry 4.0) and on minimising
environmental impact.
4. Establish research parks at selected NITs and institutes of eminence to foster incu-
bation of start-ups; build large research hubs with state-of-the-art facilities in the
area of advanced manufacturing (e.g., biomedical prototyping, etc.). Recently, the
Indian government, under the Startup India initiative for Higher Education Insti-
tutions (SIHEI), sanctioned the establishment of the research parks at IIT Delhi,
IIT Kanpur, IIT Hyderabad, IIT Kharagpur, IIT Bombay, and IISc Bangalore,
with a total sanctioned cost of 575 crores.

6.2.5 Revamp Medical Education and the Clinical Research

Ecosystem, to Train and Collaborate with Clinicians

Another equally important bottleneck in the clinical translational research ecosystem

is getting significant involvement of clinicians. Some major recommendations to
revamp education, training, and research in medical institutions are summarised in
Fig. 6.5. Many of the important points are discussed below.
First Three Years (3)
1. Develop and implement a robust innovation ecosystem in medical and dental
institutions, so that clinical research should be seen as the key way of ensuring
that the unmet healthcare needs are addressed. Medical institutions should have
an ‘Intellectual Property and Technology Licensing Cell’ to facilitate protection
of medtech IP, and to enable technology licensing.

It is recommended that final year MBBS/BDS or MD/MS/MDS students

are involved in research projects, involving clinical studies or trials of
biomaterials/implants/scaffolds in human subjects or pre-clinical studies
in large animal models.

2. Start funded masters programmes at medical colleges or non-clinical institutions,

where students can be awarded an M. Sc. or M. Tech. degree, if they do good
quality research for two years after their MBBS or BDS/MDS.
3. Design courses on research methodology, as part of the medical curriculum in
India. Faculty from good research organisations can start online courses (NPTEL
programme) that can be made available in India for guiding others. They can teach
 Revamp medical education and innovation ecosystem in medical institutes

Revamp undergraduate MBBS/BDS curriculum to include

biomedical engineering-related compulsory taught courses IIT: Indian Institute of Technology
Foster research ecosystem in Medical/Dental colleges IISc: Indian Institute of Science
Introduce “Bioengineers-in-clinics” and ‘clinicians-in-residence’ IoE: Institute of Eminence
program nationwide AIIMS: All India Institute of Medical Sciences
PGIMER: Post Graduate Institute of Medical Education & Research,
“Introduction to Biology” and “Biomaterials Science and Tissue Chandigarh
Engineering” as taught courses in academia CMC: Christian Medical College, Vellore
Common academic and research programs for basic scientists, SGPGI: Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow
engineers and clinicians
Clinical investigator fellowships for clinician scientists
6.2 Priority Recommendations for Fostering Innovation …

1 2 3 4 5 6 7 8 9 10 Years

Hospitals in academic campuses of the established IITs/IISc/IoEs

Medical Technology Parks at AIIMS/PGIMER/CMC/SGPGI etc.

Fig. 6.5 Important recommendations to revamp medical education and innovation ecosystem in medical institution
147
148 6 Recommendations

case studies and ensure that Indian research gets adequately presented in these
courses. Periodic certification based on continual learning is suggested to ensure
that the quality of students’ learning is continually monitored.
4. All of the major medical institutes, particularly AIIMS, PGIMER, SGPGI, CMC,
etc., should have one academic programme in the broad area of ‘Biomed-
ical Engineering’. Such a programme should facilitate the internship of engi-
neering undergraduates from IITs/NITs and also foster the research ecosystem
for medical undergraduates (MBBS) or masters (MD/MS) or advanced post-
graduate (DM/MCh) researchers to pursue projects on biomaterials/implants,
bioelectronics, etc.
5. Formulate and popularise nationally, specific internship programmes such as
‘bioengineering immersion programmes’ for MBBS students at an early stage
in their career, ‘clinician-in-residence’ programmes to train clinician-scientists,
‘clinical immersion’ programmes for undergraduate engineering students, and
‘bioengineers-in-clinics’ for PhD students from academia.
6. Biomaterial science is to be taught as a core compulsory subject in academic
institutions for undergraduate students in the discipline of materials science and
engineering. In most IITs, an introductory course on ‘Biology’ is taught for
undergraduate students across all the disciplines.
Importantly, IIT Kharagpur has announced that it will start an MBBS programme
from 2020.

The establishment of hospitals within academic campuses is certainly a

step forward towards a stronger translational clinical research ecosystem.

7. It is also suggested to introduce a major/minor system in the MBBS curriculum,

for related fields, such as major in pharmacy/biotechnology/biomedical science
and minor in biomaterials science. This will inspire next-generation researchers
to address cross-disciplinary research problems in healthcare.
8. Common academic and research programmes for basic scientists, engineers, and
clinicians will allow to create a research ecosystem, where clinicians, scien-
tists, and design engineers work in cross-functional collaboration. The clinical
community should be engaged through programmes, including MD-PhDs and
post-doctoral fellowship opportunities.
9. Provide clinical co-investigator fellowships or consultancy schemes for prac-
ticing clinicians, which enable them to dedicate part of their time for research
activities. Full-time research involvement of clinicians will positively influence
the translational research impact. It is also recommended to introduce more
adjunct faculty positions in medical colleges, which can be held by non-medical
faculty to enhance cross-disciplinary collaborative research work. This will allow
closer interactions with non-medical faculty and researchers.
6.2 Priority Recommendations for Fostering Innovation … 149

First Five Years (5)

1. Among all the IITs, or institutes of eminence, IIT Kharagpur has started a medical
science and technology master’s programme for MBBS students. A medical
hospital is currently being constructed at IIT Kharagpur, and the same has been
planned at IIT Kanpur. Also, several biomedical researchers at IIT Delhi collab-
orate with clinicians at AIIMS. Two recommendations are (a) establish more
such hospitals in the vicinity of other institutes to facilitate clinical translational
research, including rural areas where the topic of research is relevant to this setting
and (b) appoint clinician-scientists in dedicated clinical research laboratories in
all these hospitals.
2. Establish medical technology parks in reputed medical institutes to host Indian
biomedical implant companies. These parks will also enable to initiate inter-
disciplinary research to address clinically relevant problems (involvement of
clinicians, entrepreneurs, and basic scientists is necessary).

An ‘ecosystem’ needs to be developed at centres of excellence at various

medical institutes like AIIMS, PGIMER, Chandigarh; CMC Vellore;
SGPGI Lucknow; on advanced training for clinicians, e.g., use of robotics,
biomedical instrumentation, implant testing etc.

3. The MBBS curriculum should be revamped to introduce ‘hands on’ training,

biomedical engineering concepts, and research methodologies. Both the numbers
of research-capable doctors and their skill sets are expected to improve, if these
changes are implemented.

6.2.6 Introduce and Implement National Policies and Action

Plans to Harness Benefits of Biomaterials for the Public

All the recommendations proposed above have to align with the national policies
under the broad framework. A number of vision-related strategies are summarised
in Fig. 6.6, and those are briefly discussed below.
First Three Years (3)
1. An important recommendation would be to launch a new mission, ‘Bioim-
plants’ to accelerate innovation of biomedical implants for healthcare, which
can be mentored and supported by Prime Minister’s Science, Technology, and
Innovation-Advisory Council (PM-STIAC). The purpose of this national mission
would be to implement several of the recommendations suggested in this mono-
graph. The specific committee to be constituted under this mission would be
representatives from a number of related federal ministries of the Government of
India (Ministry of Science and Technology, Ministry of Skill Development and
 150

Introduce and implement national policies and action plans to harness benefits
of biomaterials for the public

Launch National mission ‘BioImplants’

New translational research institutes to accelerate science-to-product innovation
Online database of translational biomedical research ecosystem
Regulatory endorsement and global recognition of indigenous implants
Innovation and Roadmapping workshops

1 2 3 4 5 6 7 8 9 10 Years

Implement Healthcare related recommendations of Niti Aayog

Create strategic innovation hubs with comprehensive manufacturing,
testing and computational facility
Establish regional centers of excellence for translational research

Fig. 6.6 Major recommendations to introduce new national policies

6 Recommendations
6.2 Priority Recommendations for Fostering Innovation … 151

Union Ministry of
Health and Family Welfare
Science and Technology
Heavy Industries and Public Enterprises
Commerce and Industry
Micro, Small and Medium Enterprises
Skill Development and Entrepreneurship

Regulation
National Policies

Translation Commercialisation
Clinical and
Define
BioImplant Develop
Startups,
GLP-compliant GMP–regulated
Translational
Biocompatibility Testing Mission Manufacturing Facility
MSME,
Research Institutes Deploy Deliver Industry

Innovation
Research
GLP: Good Laboratory Practice Education Academia and
Start ups,Practice
GMP: Good Manufacturing
Industry, MSMEs Training National Labs

Fig. 6.7 Final recommendation to implement national policy for accelerated implant manufacturing
and deployment, enabling the mission ‘Healthy India’

Entrepreneurship; Ministry of Micro, Small, and Medium Enterprises; Ministry

of Commerce and Industry; Ministry of Heavy Industries and Public Enterprises,
and Ministry of Health and Family Welfare).

The objective of this national mission will be to formulate effectively and

regulate policies to manufacture and to deploy high quality, yet affordable
biomedical implants and devices for a large cross-section of Indians (see
the model proposed in Fig. 6.7).

The participation of all the ministries are necessary in view of the technological
nature of innovation, regulatory compliance, and large commercialisation poten-
tial in India and other countries, as well as societal implications. The above-
suggested mission can also implement subsidies for indigenous implants and
biomaterials, and interface regularly with insurers for refining insurance schemes.
One of the long-term objectives of this proposed mission would be to grow
the global reputation of Indian biomedical implants, devices, and translational
research.
2. Establish new translational research institutes and launch multiple research
programmes to accelerate science-to-product innovation, and to address unmet
national needs for musculoskeletal, dental, cardiovascular, neurosurgical, and
urological applications. All these programmes should be conceived and
constantly guided by clinicians from conception (problem definition) to vali-
dation (clinical trials) to marketable products (commercialisation).
152 6 Recommendations

The federal funding agencies should prioritise funding of the proposals with
an objective to conduct human clinical trials, while translating research
outcomes to marketable products.

3. Create a comprehensive online database on the entire biomedical ecosystem of

active research programmes with details of pre-clinical and clinical trial results,
as well as licensed biomedical implants/devices (indigenous/imported) having a
unique device identifier code and cost. The database should be regularly updated
with patient’s comments, revision surgeries and recalled products, etc. The portal
should be accessible to all the patients in India.
4. Constitute a national committee to oversee the promotion of indigenous implants
and to disseminate relevant information to the public so that their perceived
concerns can be dispelled. The committee should also work with relevant medical
societies and patient groups to ensure that the products are endorsed and promoted
through print/electronic media and at healthcare events. The medical fraternity
can review the clinical data extensively before giving their endorsement.
5. Promote a nationwide strategy of the ‘innovation stream’, where research is
fast-tracked by the ‘fail fast, learn fast’ approach—a cultural shift, which makes
it acceptable that innovations can undergo failures and one should learn from
failures and improve.
6. Innovation and road-mapping workshops—activity focusing on scientific explo-
ration of advanced biomaterials, challenges, foresighting, and development of
innovation strategies. One such platform can be National Frontiers of Science
(NATFOS), which is supported by the office of the Principal Scientific Advisor to
the Government of India, since 2018. Active researchers should put in all efforts
to popularise this socially relevant research area through outreach activities like
public lectures, internships, and workshops, including laboratory demonstrations
in engineering colleges/high schools, to stimulate young minds

First Five Years (5)

1. Implement the broad recommendations of Niti Aayog, the national policy body,
for health technology assessment as a basis for informed decision making and
priority setting, in corroboration with the World Health Organization’s systematic
reviews of the medical devices for use in priority populations.
2. Establish regional centres of excellence in different strategic locations of India
with evolving ecosystems, for better coordinated translational research, with
faster and regular interaction among a group of researchers from academia,
national laboratories, and industry/start-ups. An important mission of such
centres should be to provide necessary infrastructure to assess safety and effi-
cacy of medical devices, particularly on long-term clinical data, related to patient
follow up in post-operative timelines.
3. Create strategic innovation hubs with comprehensive manufacturing, testing and
computational facilities, which is essential for the accelerated development of
6.2 Priority Recommendations for Fostering Innovation … 153

biomedical devices from concepts to marketable products. The innovative busi-

ness model of the biomedical entrepreneurs should support such an ecosystem.
Funding agencies and policy makers should introduce commensurate schemes.
A final recommendation to implement national policy for accelerated implant
manufacturing and deployment, enabling the mission ‘Healthy India’ is depicted in
Fig. 6.7.
Chapter 7
Closure

Abstract This chapter portrays the author’s futuristic vision of a bright future of
biomaterials science and implants in India. This chapter is followed by the genesis
of his set of recommendations, laid down in the previous chapter, as well as a few
important pedagogical aspects for the young researchers.

This monograph will, hopefully, stimulate an accelerated journey of discovery,

together with manufacturing and commercialisation of biomedical devices and mate-
rials, in a mutually complementary manner. The goal is to deliver what India demands
and aspires to be: an international leader in the field of biomaterials and biomed-
ical implants and devices. Such an ambitious goal can be achieved by leading by
example, planning strategically, providing the necessary resources and streamlining
the innovation, regulatory, and commercialisation process. India must realise that

© Springer Nature Singapore Pte Ltd. 2020 155

B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0_7
156 7 Closure

high quality, yet affordable implants are needed to meet society’s needs, and those
of the booming medical tourism industry.
Health is at the very core of society’s fundamental strengths. Therefore, it is recom-
mended that clinicians, scientists, policy makers, and industries become inspired by
looking at some of the successful ecosystems around the globe to develop a scientifi-
cally and socially conscious platform in India, to foster a robust innovation ecosystem
within clearly defined and ethically regulated boundaries.
Despite the many scientific and medical subfields and subspecialities, the field is
united by common challenges and goals. These unifying factors make a collective
fraternity among professionals in the field, and should encourage collaborative efforts
in the right direction. This text speaks to the moment and beyond. It is addressed to
all consumers of science and medicine, critical as well as lay. It is a first of its kind
road-map that can assist India to take a leading role in the flight of domestic frontier
science and medicine, and regulatory policy, from the realm of the institutions to the
markets catering to the needs of society.
A new era of advanced, high-value world-class biomaterials, biomedical devices
and implants is coming. Is India ready?
Appendix
Pedagogy and the Genesis of this Book

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B. Basu, Biomaterials Science and Implants,
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Appendix A
Defining Key Elements of Biomaterials Science

The definitions in this section are reproduced from ‘Definitions of Biomaterials for
the Twenty-First Century’, a review of key, critical biomaterial terms, and definitions
endorsed by the International Union of Societies for Biomaterials Science and Engi-
neering. The author attended this meeting and deliberated in the discussion with the
global leaders in the field, leading to the finalisation of the following definitions.

Bioactivity A phenomenon by which a biomaterial elicits or modulates biological

activity.

Bioceramic Any ceramic, glass, or glass–ceramic that is used as a biomaterial.

Biocompatibility The ability of a material to perform with an appropriate host

response in a specific application.

Bioelectronic Implant Implants that could send an electrical pulse to a major nerve
to alter the commands an organ receives, and thereby control its function.

Biofabrication The production of complex living and non-living biological prod-

ucts from raw materials such as living cells, molecules, extracellular matrices, and
biomaterials.

Bioink Cell-laden biomaterial that can be integrated into additive manufacturing

processes to print 2D and 3D structures.

Biomaterial Material designed to take a form which can direct, through interactions
with living systems, the course of any therapeutic or diagnostic procedure.

Biomaterials Genome Integration of computational tools, large databases, and

experimental techniques to explore the basic material elements and combine them
to discover and design new biomaterials for medical products.

Biopolymer A polymer synthesised by living organisms.

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160 Appendix A: Defining Key Elements of Biomaterials Science

Bioprinting The use of 3D additive manufacturing technology that typically incor-

porates one or more biological components, viable cells, growth factors, and/or
bioactive materials.

Biosensor A device used to detect the presence or concentration of a biological

analyte.

Blood Compatibility/Haemocompatibility The ability of a blood-contacting

biomaterial to (1) avoid the formation of a thrombus by minimal activation of platelets
and of blood coagulation, (2) minimise activation of the complement system, and (3)
minimise haemolysis.

Cell Therapy The process of introducing new cells into a tissue in order to treat
disease.

Controlled Release Release of a solute, drug, diagnostic, or therapeutic agent from

a carrier, system, or device in a planned predictable manner.

Drug Delivery Delivery and/or release of therapeutic and/or diagnostic agents.

Drug Eluting A device which (slowly) releases a drug to prevent cell proliferation.

Extracellular Matrix The composite material (ECM) in and between cells with
both structural and regulatory function. ECM is composed of collagens, fibronectin,
elastin, fibrillins, enzymes, proteoglycans, glycosaminoglycans, and others.

Gene Therapy The transplantation of normal genes into cells in place of missing
or defective ones for the treatment of genetic disorders.

Graft Piece of viable tissue or collection of viable cells transferred from a donor
site to a recipient site for the purpose of reconstruction of the recipient site.

Growth Factors Proteins that stimulate the activity of genes required for cell
growth and cell division and may also mediate cellular migration, differentiation,
and synthetic activities.

Hydrogel A physically or chemically cross-linked polymer, swollen in water or

biological fluids.

Immunotherapy A treatment which elicits or suppresses an immune response.

Implant A medical device made from one or more biomaterials that is intentionally
placed, either totally or partially, within the body.

Inflammation The response to injury and/or contact with biomaterials, involving

a cascade of activation with blood cells and humoral factors, and both acute and
chronic inflammation. In the case of implanted devices, this may lead to resolution
with fibrous capsule formation and remodelling; with ex vivo devices, this may lead
to systemic effects.
Appendix A: Defining Key Elements of Biomaterials Science 161

Mechanotransduction The processes by which cells sense mechanical stimuli and

convert them to biochemical signals that elicit specific cellular responses.

Microfluidics The behaviour, control, and manipulation of fluids that are geomet-
rically constrained to small, typically submillimeter, scale.

Nanomaterial Material with one or more external dimensions, or an internal struc-

ture, which could exhibit novel characteristics compared to the same material
without nanoscale features.

Nanoscale Having one or more dimensions of the order of 100 nm or less.

Nanoparticle Particle with one or more dimensions at the nanoscale.

Nanotechnology The science of manipulating materials at the submicron level.

Organoid Self-organised three-dimensional tissues are typically derived from stem

cells and embedded in a matrix, and mimic key functional, structural, and biological
complexity of an organ.

Osseointegration The capability of substrate-adherent osteoblasts to produce bone.

Osteoclast Large multi-nuclear cell associated with absorption and removal of bone.

Osteoinduction Action or process of stimulating osteogenesis.

Prosthesis Device that replaces or supports a body part.

Remodelling The constant process of ECM and fibrous capsule collagen degrada-
tion and synthesis initiated and controlled by chemical, physical, mechanical, and
other properties of the biomaterial in the in vivo environment.

Regeneration Synthesis, renewal, or growth of new functional tissue which has

been lost due to injury, congenital deficiency or has failed due to ageing or disease.

Regenerative Engineering The integration of advanced materials sciences, stem

cell science, engineering, developmental biology, and clinical translation for the
regeneration of complex tissue and organ systems.

Regenerative Medicine Therapies that treat disease, congenital condition, and

injury by the regeneration of functional tissue or organ structures.

Scaffold A biomaterial structure which serves as a substrate and guide for tissue
repair and regeneration.

Self-assembly The autonomous organisation of components into patterns or struc-

tures without human intervention.

Stent A tubular support placed in a blood vessel, canal, or duct to aid healing, prevent
or relieve an obstruction or stenosis.
162 Appendix A: Defining Key Elements of Biomaterials Science

Surface Topography Delineation of the natural and artificial features of a surface

from a flat plane.

Targeting A process of drug or therapeutic agent delivery only to the desired site
of action.

Template Biomaterials-based construct of defined size, chemistry, and architecture

that controls the delivery of molecular and mechanical signals to target cells in tissue
engineering processes.

Therapeutic Agent A substance used to treat a disease or other medical condition.

Tissue Engineering The use of cells, biomaterials, and suitable molecular or phys-
ical factors, alone or in combination, to repair or replace tissue to improve clinical
outcomes.

Transplant Tissue structure, such as a complete or partial organ, that is transferred

from a site in a donor to a recipient for the purpose of reconstruction of the recipient
site.

Whole Organ Engineering The engineering of replacement organs that results in

the preservation of tissue-type-specific matrix in a 3D architecture that closely mimics
the native tissue and seeks to provide organ-specific functionality.

For e-learning resources, please see the National Programme on Technology

Enhanced Learning (NPTEL) online courses, offered by the author;
1. Introduction to Biomaterials (https://nptel.ac.in/courses/113104009/)
2. Biomaterials for Bone Tissue Engineering Applications (https://www.youtube.
com/playlist?list=PLLj8usx87A_b16gYoCJclV9ADCgnre0tq)
Appendix B
Ethical and Safety Considerations

Good laboratory practice (GLP) provides a framework of principles and stan-

dard operating procedures that establishes an ethically acceptable framework for any
in vitro/in vivo study to produce reliable and high-quality results/outcomes. These
studies should be planned, performed, monitored, reported, and archived according
to GLP. GLP therefore assures regulatory authorities that the data in a report comply
with the standard guidelines.
The ethical way to procure standard stem cell lines is from the stem cell banks
that are available worldwide. These places store the cell lines under biologically
appropriate conditions, which are further used for regenerative medicine and therapy.

Documentation for Ethical Clearance

The following are the documentations for ethical clearance that one is recommended
to comply with:
• Proof of institutional ethical and legal approvals
• Donor informed consent documents
• Confidentiality on the information of donor
• All scientific details, like culture conditions, passage number, etc.
The investigator should read the ICMR-DBT ‘Guidelines for Stem Cell Research
and Therapy’. The documentation requires stating the kind of stem cells being used
and its culture protocol in detail with information of the name of reagents being used,
media composition, recovery and expansion of stem cells from frozen stock, their
subculturing methods, and cryopreservation technique.
Every country has a different set of stem cell guidelines. The Indian Council
of Medical Research (ICMR) in India last released the revised version of ‘Ethical
Guidelines for Biomedical Research on Human subjects’ in 2017. This document
enlists requirements and conditions for carrying out ‘stem cell research and therapy’

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164 Appendix B: Ethical and Safety Considerations

(SCRT). The investigators of a laboratory should ensure that the cell lines are main-
tained and used according to the guidelines of the document, as mentioned in the
Material Transfer Agreement (MTA). While using stem cells, an investigator should
declare the level of manipulation, that a given stem cell line is expected to experience
during culture on biomaterials.

Recommended Guidelines for Biocompatibility Evaluation

Techniques and expertise from multiple disciplines, including biological and medical
sciences, need to be combined for pursuing new research programmes in an
interdisciplinary field, like biomaterials science. Clearly, there is a high need to
incorporate ethical guidelines for conducting safe research in this field. This challenge
deals with the fundamental principles and standard culture protocols for different
cell types, including stem cells, preclinical studies, and clinical trials. This section
includes the ethical guidelines for in vitro assays in a laboratory, and how to maintain a
cell culture facility within a safe physiological environment. Additionally, biological
assays that quantify cell viability, toxicity, differentiation, and cell fate processes are
discussed in detail. This section outlines the ethics, and laboratory safety rules that
are defined for conducting both in vitro and in vivo experiments with biomaterials.

No. Recommended guidelines for biocompatibility evaluation

1. Approval from the biosafety committee of the institution for setting up a cell culture
facility in a laboratory and for conducting in vitro cell culture-related experiments. In
addition, institutional stem cell committee’s approval to conduct any study using stem cells
2. The cells at their optimal growth stage need to be certified as healthy before testing the
biomaterial on them. It is recommended to use n < 5 (n = passage number)
3. For cell culture studies, the researcher should grow the cells in 3–4 times interval,
depending upon the cells’ doubling time. The MTT/LDH assays will be used to quantify
cell viability, while fluorescence microscopy/scanning electron microscopy should be used
for recording cell morphological changes. For polymeric or carbonaceous biomaterials, it
is recommended to use the LDH assay
4. For the biochemical assays, the reagents should not interfere or react with the biomaterial
substrate constituents, in order to avoid errors
5. The systematic increase in the cell numbers indicates positive compatibility of the
biomaterial substrate with the cell line, and therefore culture experiments are to be
conducted over 3–4 timepoints, depending on doubling time
6. More than one cell type should ideally be used for testing the application of the
biomaterial. For example, for bone replacement, fibroblast and osteoblasts can be used;
while for neural applications, neuroblastoma and Schwann cells can be used
7. Both positive and negative controls, along with benchmark controls, are highly
recommended for biocompatibility assessment
8. Approval from the human ethics committee of the institution for conducting
haemocompatibility studies that require usage of human tissue cells or human blood
(continued)
Appendix B: Ethical and Safety Considerations 165

(continued)
No. Recommended guidelines for biocompatibility evaluation
9. For blood compatibility assay studies, ISO guidelines need to be followed. This requires
soaking the biomaterial at 37 °C for 30 min followed by recording the blood parameters
10. Statistical software programs (SPSS, ANOVA, students’ T-test, etc.) are to be used to
estimate significance should be used while analysing the
cytocompatibility/haemocompatibility data in any research publication or scientific
document. A biostatistician can also be consulted in such cases
Appendix C
International Research Groups

A summary of the research activities in different groups around the world is presented
below. This list, however, does not contain all the key international research groups,
and many of these have carried out seminal work in the field of Biomaterials.

C.1 North America

Rajendra Bordia, Clemson University, South Carolina, USA His team inves-
tigates porous biomaterials for bone and joint implants. Stress shielding in solid
metallic load-bearing bone replacement implants (e.g. hip stems) arises from a stiff-
ness mismatch between the higher stiffness implant and the lower stiffness bone. This
is believed to contribute to implant loosening and the need for a highly undesirable
revision surgery. Bordia’s group has used elective electron beam melting, to create
engineered porous structures with controlled porosity and pore size in Ti-6Al-4V
alloy. The group was the first to investigate the fatigue properties of these materials.

David Kaplan, Tufts University, USA The lab focuses on biopolymer engineering
to understand structure-function relationships, with an emphasis on studies related
to self-assembly, biomaterials engineering, tissue engineering and regenerative
medicine. In addition, the lab has pioneered the study of silk-based biomaterials
in regenerative medicine. His past contributions have resulted in the emergence of
silk as a new option with excellent biocompatibility in the degradable polymer field,
and new tissue-specific outcomes with silk as scaffolding in gel, fibre, film or sponge
formats, with complex 3D tissue co-culture systems.

Cato Laurencin, University of Connecticut, USA The world-renowned group is

working on regenerative engineering (a field Laurencin has founded), nanotech-
nology, polymeric materials science, bioreactor technology, drug delivery systems,
morphogenesis, and stem cell technologies. The group, which was the first to publish
on nano-fibre technologies for biomedical purposes, and the first to develop clinical

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168 Appendix C: International Research Groups

polymer ceramic systems for bone regeneration, is now working on the development
of whole limb regeneration using new paradigms in regenerative engineering.

Nicholas Peppas, University of Texas at Austin, USA He has provided new

insights into biomaterials design and development, drug delivery systems and
advanced, intelligent, feedback controlled biological systems. The group is known
for its work on compatible, cross-linked polymers (hydrogels), which have been used
as controlled release devices, especially drug delivery, peptides and proteins, devel-
opment of novel biomaterials, biomedical transport phenomena, and biointerfacial
problems.

John A. Rogers, Northwestern University, USA He leads a vibrant research

group that seeks to understand and exploit interesting hybrid combinations of poly-
mers, liquid crystals, and biological tissues, to induce novel electronic and photonic
responses in these. Current research focuses on soft materials for conformal elec-
tronics, nanophotonic structures, microfluidic devices and microelectromechanical
systems, with bio-inspired and bio-integrated technologies.

Molly Shoichet, University of Toronto, Canada She leads a group in researching

biomaterials for regenerative medicine, tissue engineering and drug delivery. Her
research program focuses on strategies to promote tissue repair after traumatic spinal
cord injury, stroke and blindness and enhance both tumor targeting through innovative
strategies and drug screening via 3D cell culture with new hydrogel design strategies.

C.2 Europe

Serena Best, University of Cambridge, UK The group has developed a range

of synthetic substituted hydroxyapatite (HA) materials with physiologically rele-
vant ionic lattice substitutions, for skeletal defect-filling and as scaffolds for tissue
engineering. Her group is also working on bioactive and bioresorbable composites
for tissue engineering, including biodegradable polymers, and bioactive ceramics,
glasses and glass ceramics as fillers. One of her current research themes is to develop
collagen-GAG based scaffolds for dental restorations, heart tissue repair and the
production of platelets.

Aldo Boccaccini, Institute of Biomaterials, Erlangen, Germany His research

group is developing nanostructured biomaterials for medical implants, tissue engi-
neering of bone, cartilage and cardiac tissue and drug delivery. In bone tissue engi-
neering, Aldo’s group is focused on controlling surface topography and chemistry
of 3D tissue engineered scaffolds, to enhance growth of new bone tissues and vascu-
larisation. For cardiac tissue engineering, nanostructured polymer biomaterials are
being developed as cardiac patches.
Appendix C: International Research Groups 169

Marc Bohner, RMS Foundation, Switzerland Their research focus has been
biomaterials, in particular bone graft substitutes and calcium phosphates. This
comprises synthesis, nanostructuration and use of various calcium phosphates, the
improvement of delivery techniques for bone substitutes and application of these
materials, methods, and concepts in clinical use. The RMS Foundation is a research
and testing institute offering testing services in the fields of medical and materials
technology as well as mechanical process engineering.

Sarah Cartmell, University of Manchester, UK Her group is researching transla-

tion of novel tendon repair products, mechanotransduction in human mesenchymal
stem cell differentiation, design of a novel co-culture bioreactor for osteochon-
dral tissue-engineered plugs, use of statins for influencing osteoblast proliferation
and differentiation, electrical stimulating bioreactors for modulating stem cell fate
process and ligament tissue engineering.

Jérôme Chevalier, Institut National des Sciences Appliquées (INSA), Lyon,

France His group is known for pioneering research on low temperature degradation
of ZrO2 bioceramics and developing new ZrO2 -based biocomposites for muscu-
loskeletal applications, as well as for conducting many performance-limiting tests
(e.g. Hip simulator test).

Christophe Drouet, CIRIMAT, Toulouse, France His team extensively uses

biomimetic nanocrystalline apatites for production of highly bioactive bone scaf-
folds towards activation of existing biomaterials with low bioactivity. The high
resemblance to bone mineral allows envisioning original applications beyond bone
regeneration—increasingly appealing in view of ever-more challenging applications
in medicine, whether for bone tissue engineering or nano-medicine.

Michael Gelinsky, TU Dresden, Germany His lab is working on biomaterials

design for hard and soft tissues, scaffold-based tissue engineering and transla-
tional musculoskeletal medicine. Selected ongoing projects are material develop-
ment for 3D printing and bioprinting applications, therapeutic drug/ protein delivery
biomimetic bone matrices and biomaterials for articular cartilage defect healing.

Julian Jones, Imperial College London, UK His group is conducting research on

strong porous scaffolds for regenerative medicine, porous materials for minimally
invasive diagnosis, tough sol-gel hybrids, therapeutic nanoparticles, processing of
glasses, bioactive materials, sol-gel chemistry and cell responses to biomaterials.
Jones’ research group has done seminal works on bioglasses, including nanoparticles,
that can deliver therapeutic ions inside cells and “bouncy bioglass,” sol-gel hybrid
materials that can take cyclic loads, with mechanical properties that can be matched
to that of host tissue.

Anne Leriche, Université Polytechnique Hauts-de-France, France Concerning

bone substitute fabrication, she has a great expertise in calcium phosphate ceramic
powder synthesis by coprecipitation method and in macroporous ceramics processing
by three different methods. Current research concerns the impact of the ceramic part
170 Appendix C: International Research Groups

surface modified by laser patterning on cell colonisation. The second interesting

expertise of the lab is the microwave assisted sintering, a new and original sintering
technology allowing densifying ceramics faster than conventional heating techniques
while maintaining equivalent and sometimes higher mechanical properties. This tech-
nology has successfully been applied to CaP macroporous scaffolds with consider-
able sintering time duration reduction. Thirdly, the lab is working on the synthesis
and purification of polypeptides which exhibit osteoinductive and/or antibacterial
properties using molecular biology techniques. The synthesised polypeptides are
composed of dual protein, combining a collagen-like structure and an antibacterial
peptide of human sequence to limit the immunogenicity risks. The polypeptides are
grafted onto dense or porous ceramic parts to promote more rapid integration of the
implant and to reduce bacterial infections post-surgery.

Ivan Martin, University Hospital of Basel, Switzerland His laboratory develops

three dimensional in vitro model systems to explore fundamental facets of tissue
development. The engineered nasal cartilage grafts developed in his laboratory have
been successfully implemented in a phase I human clinical trial for nasal reconstruc-
tion after tumor resection. Another conclusive phase I clinical study using similar
grafts for the regeneration of articular cartilage in the knee after traumatic injury has
enabled to progress to the ongoing multicenter phase II human clinical trials to treat
knee cartilage injuries. The applicability of engineered and decellularised tissues
as templates for bone regeneration has been successfully tested and published by
his team in high impact factor journals. For example, his laboratory is amongst one
of the few tissue engineering laboratories that combine the principles of develop-
mental biology to develop bone and cartilage tissue simulating events of embryonic
development. Furthermore, his team has developed various bioengineering platforms
like the bioreactor systems for the direct perfusion of culture medium and cellular
suspensions through the engineered 3D constructs, and some are commercialised.

Abhay Pandit, National University of Ireland, Galway His research group has
developed functional, biocompatible building blocks for targeted, controlled, drug-
release and delivery systems. In addition, micro- and nano-structured implants and
devices designed to emulate fundamental cellular architecture have facilitated clinical
translation of cell-based devices.

Jouni Partanen, Aalto University, Finland The group conducts research in the
field of Additive Manufacturing (AM). The emphasis has been in industrial appli-
cations of AM of the technology, including the potential new business models this
digitally driven production method makes possible. The group also develops new
variations of AM and other digitally driven production methods. In the medical field,
the group has been involved in research and development to generate custom implants
and medical products from person-specific scanned medical data.

Rui Reis, University of Minho, Portugal He is leading a vibrant research group

on 3B (Biomaterials, Biodegradables and Biomimetics). Major research areas at
his group include new materials development, drug delivery, tissue engineering,
Appendix C: International Research Groups 171

regenerative medicine, nanomedicine, and stem cell isolation and differentiation.

Their goal is to develop novel biomaterials based on natural polymers for applications
in drug delivery and tissue engineering of bone, cartilage and skin.

Jukka Seppälä, Aalto University, Finland His research combines the frontline
biopolymer research with fast-developing digitisation, additive manufacturing and
biomedical sciences. His research group is one of the global leaders in the biopolymer
structure property correlation research. His research has led to groundbreaking results
in polymer-based controlled therapeutic agents release systems, extremely strong
orthopaedic fixation devices and additive manufactured scaffolds for tissue regener-
ative purposes. The key collaboration partner in the development of biomedical appli-
cations for nerve and bone regeneration has been Prof. Ashok Kumar of IIT Kanpur
and his group. This collaboration has led to breakthroughs in nerve regeneration
through 3D-printed and cryogel filled nerve conduits.

Anna Tampieri, Istituto di Scienza e Tecnologia dei Materiali Ceramici (ISTEC),

Italy She leads the Bioceramics Research Group, focusing on the synthesis of
bioinert and bioactive ceramics, like HA, TCP and non-stoichiometric apatites. In
particular, her group aims to develop porous ceramics for bone tissue replacement
and modulated drug delivery. Tampieri’s group also works on biologically inspired
CaP–based composites, such as HA/collagen.

C.3 Asia-Pacific

Dietmar W. Hutmacher, Queensland University of Technology, Australia The

group has three main areas of research: cartilage, bone graft and 3D cell cultures.
In the area of cartilage, the group’s work on the molecular characteristics of zonal
chondrocytes under dynamic cell culture conditions can lead to the development of
a novel cartilage engineering technology platform that will allow for treatment of
elderly patients and larger defects. Regarding bone graft, the group hypothesise that
a composite scaffold (already successfully utilised in low-load bearing bone defects)
can be biomechanically optimised and be combined with controlled delivery of
angiogenic (PDGF/VEGF) and osteoinductive (BMP) molecules producing biolog-
ically active engineered bone graft systems with mechanical properties suitable for
load-bearing applications.

Laura Poole-Warren, University of New South Wales, Australia She leads a

research group in biomedical engineering focussed on design and development of
novel materials for neural electrodes and other soft-tissue interfaces, and on 3D
engineered neural tissue models. A key theme of her work is on design of new
biosynthetic materials and understanding material and device interactions with cells
and tissues. Her group also studies hydrogel drug delivery, biomaterials for wound
healing, tissue engineering percutaneous access catheters and vascular grafts.
172 Appendix C: International Research Groups

Yarlagadda Prasad, Queensland University of Technology, Australia His lab

conducts research on nanopillar surfaces and surface modifications with bactericidal
effect on titanium implants, additive biomanufacturing and bending of fracture fixa-
tion plates in orthopaedic surgery. Also, his research group is investigating antiviral
and antibacterial nanostructured surfaces for hospital applications.

Seeram Ramakrishna, National University of Singapore His lab is working on

electrospinning and nanostructured materials. He demonstrated that nano-fibres are
the ideal scaffolds to provide biomimetic microenvironment for different cells in
tissue engineering application. His team is now investigating the use of their patented
nanoyarn and 3-D nanofibrous scaffold in stem-cell capture and expansion. Seeram’s
team successfully used nano-fibres with metal oxides and organic molecules to detect
and neutralise chemical warfare agents, such as, nerve gas and mustard gas, more
effectively than the current systems.
Appendix D
Conferences and Workshops

This section includes summaries of events, wherein extensive discussions took place
over the last three years. Many such discussions allow the author to gain an under-
standing of the status and challenges in the field of biomaterials and implants in India.
There are several technical details that were discussed which are not summarised
here, since they are out of the scope of this monograph.

Clinical-Focused Workshop: New Materials for Healthcare:

Idea Generation Workshop at Hotel Oberoi, Bangalore, 6 May
2018

The Indian Institute of Science (Bangalore) and Tata Steel New Materials Business
hosted a unique conclave, ‘New Materials for Healthcare’ at Hotel Oberoi, Bangalore,
on 6 May 2018. The event was endorsed by the American Ceramic Society. The
central objective of this conclave was to understand the challenges faced by the
active clinicians, which remains to be addressed with translational research involving
innovative biomaterials. The conclave brought together 12 clinicians in the fields of
orthopaedics, dentistry, neurosurgery, ear, nose and throat (ENT), and urology. There
were seven representatives from six industries, nine young faculty colleagues from
IITs and IISc, and nine young researchers. There were five focused sessions in the
conclave which were moderated by academic researchers. Each session started with
a clinician’s presentation, followed by presentations of academic researchers and
industry representatives. Each session ended with a panel discussion on the session
theme.

1. Orthopaedics

In this session, the pros and cons, mechanical properties and issues of cost, and
quality of titanium and stainless steel implants were discussed. The problem of
Ti-based screws getting stuck in the implant during fracture fixing surgeries was
© Springer Nature Singapore Pte Ltd. 2020 173
B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0
174 Appendix D: Conferences and Workshops

discussed. Potential solutions are the usage of PEEK polymeric screws and the usage
of additive manufacturing as a technique for developing patient-specific implants
and accessories. Recent advances in the use of a biodegradable polymeric scaf-
fold in orthopaedic applications for osseointegration and reunion of fractures were
discussed.
The problem of osteoarthritis, which is associated with chronic joint pain, was
discussed. The potential solution is an implant with improved wear resistance and
mechanical strength. Development of a chondrogenic scaffold and injectable carti-
lage are potential solutions to osteoarthritis. Osteomyelitis is associated with infec-
tion at the fracture site of bone which might spread to the nearby tissue. There exists a
need for an affordable solution. Biocomposite mixed with antibiotics (STIMULAN® )
is already in the Indian market, but the price is still not easily affordable.

2. Neurosurgery

During this session, the design of materials that improve interaction between neurons,
bone, and meninges was discussed. Also, prevention of the formation of scar tissue
by astrocytes is extremely important for neurological/cranial-based applications.
Three main applications were highlighted: childhood skull deformation, adult skull
deformation, and duraplasty. For the first two applications, the problems associ-
ated with titanium implants were discussed. For duraplasty, the pros and cons
of polypropylene- and collagen-based implants were discussed. For the craniec-
tomy application, titanium- and stainless steel-based alloys have been established
as the most promising implant materials. However, cost is a major limiting factor.
Biodegradable polymers are most widely used in cranial applications, as screws and
cranial plates; however, breakage during implantation is a disadvantage.

3. Urology

Malignancy in the bladder, urethra, and kidneys are major clinical applications. There
is a current need for a new material for replacing the bladder in bladder transplan-
tation. The neo-bladder should have the right mechanical properties and should be
encrustation resistant. For surgery related to the urethra, doctors require a biodegrad-
able material for stents. During kidney surgery, there is need for a haemostatic agent
which can stop blood flow temporarily without a need to clamp the blood vessels.
There is need for an affordable reusable organ retrieving bag made from a new poly-
meric material, which should stay intact during the surgical procedure. For inconti-
nence, there is need for a device which can manage the flow of urine into a urinary
bag.

4. ENT: Cochlear implants

Insertion trauma and long-term inflammatory damage to hair cells leading to loss of
residual hearing is a key application. Cochlear implants are one option for treatment
of hearing loss. Development of an affordable indigenous implant is preferred since
the cost of imported implants is high. Development of an electrode material with
improved biocompatibility is needed.
Appendix D: Conferences and Workshops 175

5. Dental

Three areas for potential innovation were discussed. Abfraction is a physico-

mechanical loss of tooth architecture that is not caused by tooth decay, located along
the gum line. This affects mostly the enamel and the dentin part of the crown. Devel-
opment of moderate and steady peptide-releasing biomaterials which will be able to
regenerate or cure the area as well as a temporary supporting material in the affected
region may be a probable solution. Affordable digital impressioning is to be devel-
oped which will allow the surgeon to reconstruct tooth structures using CAD/CAM
technology only by relying on the digital scan of the neighbouring dental architec-
ture. Caries can be described as cracks, channels, pits, grooves, and cavities in tooth
structure which can originate in the back teeth, between teeth, around dental filling or
bridgework, and/or near the gingival margin. Development of a suitable biomaterial
which will be able to form a strong and long-term bond with dentin for treatment of
caries can be a potential solution.

Biomaterialomics—Focused Workshop: ICME Approaches

to Innovation in Biomedical Implants Workshop at IISc,
Bangalore, 10–12 August 2018

The Indian Institute of Science (Bangalore) and ICME National Hub@IIT Kanpur
hosted the National workshop ‘ICME Approaches to Innovation in Biomedical
Implants’ from 11 to 12 August 2018 along with a pre-workshop tutorial on 10
August 2018 at the Materials Research Center, Indian Institute of Science, Banga-
176 Appendix D: Conferences and Workshops

lore. This event was additionally supported by the DBT Bioengineering and Biode-
sign Initiative and the DBT Centre of Excellence on Biomaterials, and was organised
as one of the activities of the DST-SERB-funded Vajra scheme to Professor Surya
R. Kalidindi from Georgia Institute of Technology and Professor Bikramjit Basu
from Indian Institute of Science (Bangalore). The workshop was endorsed by the
American Ceramic Society, the Biomedical Engineering Society and the Society of
Biomaterials and Artificial Organs.
In the pre-workshop tutorial aimed at introducing cutting-edge research topics to
young researchers (i.e. graduate students and post-doctoral students), Prof. Kalidindi
delivered a series of lectures on the foundational elements of the emergent Integrated
Computational Materials Engineering (ICME) and Materials Genome Initiative
(MGI), whose goal is to accelerate dramatically the rate at which new and improved
materials (including biomaterials) are designed, developed, and deployed in biomed-
ical applications. Additionally, a number of experts from complementary fields of
expertise of central focus to the workshop (including biomaterials, bioimplants, and
bioengineering) also presented lectures in the pre-workshop tutorials. The topics
covered in the pre-workshop included statistical quantification and low-dimensional
representation of material structure, techniques for the measurement of micro-
structures over multiple length scales, accelerated development of high-performance
materials using machine learning, formulation of process-structure-property (PSP)
linkages using machine learning tools, phase-field modelling in ICME, molecular
dynamics simulations in modelling of biomaterials, high-throughput experimental
assays for PSP linkages, quantitative biology of the cytoskeleton, immune response to
biomedical implants, and tissue engineering applications in cardiovascular surgery.
The main workshop explored the cutting-edge research opportunities and potential
benefits from the application of ICME-based approaches to the design and devel-
opment of implantable biomaterials. In the field of materials science, new protocols
are being developed for the extraction of reliable and robust PSP linkages from
all available experimental and simulation data sets. It is anticipated that the formal
application of these techniques to implantable biomaterials will lead to acceler-
ated and rational development of biomedical implants and devices. The lectures
and discussions in this workshop deliberated on topics such as clinical challenges
in the successful deployment of biomedical implants, indigenous manufacture of
bioimplants, and the multi-scale physics-based simulations for integrated materials,
product design, and development. A common thread in all the discussion was the
new opportunities afforded by the emergent tools in data science and informatics
for circumventing many of the current challenges in the biomaterials/bioengineering
fields. In particular, there was excitement that these new tools can help address the
current major gaps in our fundamental understanding of how the microstructure and
material composition influence cell functionality, bone remodelling, genotoxicity,
and osseointegration. It was broadly understood that a physics-based understanding,
capturing, and exploiting of the principles of biocompatibility in a consistent PSP
framework would allow for a rational design of bioimplants. It is expected that future
Appendix D: Conferences and Workshops 177

research at the intersection of biomaterials, bioimplants, materials science, manu-

facturing, data sciences, and informatics holds tremendous promise for arriving at
new and improved materials at dramatically reduced cost and effort.
The workshop brought together 35 speakers, which include academicians, clini-
cians, and industrialists. There were 5 representatives from 4 industries, 5 clinicians,
25 faculty colleagues from IITs, NITs, and IISc, and 25 young researchers. There
were nine sessions chaired by different experts in the field. There was also a panel
discussion with lively discussion among all of the attendees. The panelists included
leaders from academia, government, and industry.

National Status and Road-mapping Workshop: Fundamentals

of and Clinical Perspectives on Implantable Biomaterials
23–24 August 2019

A one and a half day workshop was held from 23 to 24 August 2019, at Indian Institute
of Science, Bangalore, featuring Prof. Sarah Cartmell, from the University of Manch-
ester, foreign Principal Investigator under the Scheme for Promotion of Academic and
Research Collaboration (SPARC). The event was hosted by Prof. Bikramjit Basu,
Principal Investigator of the project. The presentation sessions explored ongoing
research in the field of biomaterials science, tissue regeneration, and bioengineering,
India, and were open to students of Indian Institute of Science. Faculty presenting
were from IIT (BHU), Varanasi, NITK Surathkal, IIT Kharagpur and IIT Roorkee.
178 Appendix D: Conferences and Workshops

The workshop featured one-to-one discussions of faculty with Prof. Cartmell. Prof.
Basu discussed challenges and recommendations associated with the current research
ecosystem, in preparation for publishing a monograph for the Indian National Science
Academy on the subject. How to map the terrain ahead for improving research on
indigenous biomedical implants and the related ecosystem were deliberated on.

International Conferences and Symposia

International Symposium ‘Fundamentals of and Clinical

Perspectives on Biophysical Stimulation of Cells
on Implantable Biomaterials’—GFMAT-2 and Bio-4
at Toronto, Canada, 21–26 July 2019

In the interdisciplinary field of biomaterials, the phenomenological interaction of a

biological cell on a material substrate under normal culture conditions is broadly
known, and researchers use many approaches to tailor substrate modulus or surface
wettability in an effort to enhance cell–material interaction. In this context, a strik-
ingly different approach in the field of biomaterials science has recently been
proposed to replicate the dynamic physiological micro-environment of native tissues.
Using experiments and modelling approaches, the recent research has witnessed a
new dimension to the design of biomaterials by developing an integrated approach
towards the development of new culture platforms and to carry out thought-provoking
experiments to generate a fundamental understanding on the external field-mediated
cellular functions. To discuss recent advances, a special symposium was organised
by Bikramjit Basu. This symposium was attended by experts on biomaterial develop-
ment, biology, medicine. Effective discussions on the research collaborations were
also important subjects for future international projects. A forum such as this confer-
ence is expected to accelerate progress of the biophysical stimulation approach for
human healthcare applications.

International Conference on the Design of Biomaterials

(BIND 12) and the Young Scientist Training Workshop
(BIOMAT 12) at Indian Institute of Science, Bangalore, 9–12
December 2012

The global biomaterials market is estimated to be worth $88.4 billion USD by 2017.
A rise in musculoskeletal disorders further enlarges the scope of biomaterials in
healthcare, which impose a burden of >$250 billion USD every year on society. It is
Appendix D: Conferences and Workshops 179

interesting to note that North America has the largest biomaterials market share in
the world. However, the Indian market is slowly emerging.
In lieu with the emerging trends, a three-day international conference on design
of biomaterials (BIND 12) was organised at Indian Institute of Science, Bangalore
in December last year to (i) identify problems associated with biomaterials design
and fabrication, (ii) review the progress being made in this important area in India
vis-à-vis the rest of the world, (iii) discuss the development of novel techniques inte-
grating nanotechnology, stem cell, or regenerative medicine and tissue engineering
and (iv) to serve as a platform for young researchers to present their results before
the biomaterials community.
BIOMAT-12, a workshop preceded the conference, which was inaugurated by K.
B. R. Varma (Chairman, Materials Research Centre, IISc). The main objective of
the pre-conference workshop was to educate and train the next generation of Indian
biomaterial researchers, and to interface with the Department of Science & Tech-
nology and Defense Research and Development Organization. The workshop was
designed to cover basic concepts such as structure, properties, processing, and char-
acterisation of biomaterials, and the evaluation of blood, cell, and bacterial compat-
ibility of materials, to advanced topics such as tissue scaffolds, drug delivery, and
imaging. Lectures were supplemented with demonstrations and laboratory visits.
Overall, the workshop served as a platform to disseminate information to future
stakeholders on the subject through a series of classroom lectures and laboratory
training sessions.
The design and development of biomaterials require integration of concepts and
expertise of two widely different disciplines—materials science and engineering and
biological science. In order to ensure the continuous growth of this emerging field,
numerous initiatives have been taken at the Indian Institute of Science, Bangalore.
Also, several academic courses are being taught at the undergraduate and graduate
levels in top most universities, including the IITs. M. S. Valiathan, the brain behind
India’s first artificial heart valve emphasised on the need for developing biomed-
ical devices, and stressed that the events, like BIOMAT 12 workshop and BIND 12
conference, would act as a catalyst to stimulate young minds towards creating afford-
able healthcare in India. P. Balaram (former Director, IISc) stated the growing need
for interdisciplinary research, education, and introduction of recent interdisciplinary
programmes at the interface of engineering and biological sciences.
Different aspects of research related to the development of orthopaedic bioma-
terials, cell–material interactions, novel biopolymers, nanobiomaterials, and tissue
engineering were discussed by 33 invited speakers and was attended by close to 200
delegates from USA, Belgium, Germany, UK, France, Portugal, Nepal, and various
Indian institutes.
The advent of nanotechnology has made a significant impact on many areas
of our lives, in particular, the area of electronics with faster and smaller devices
flooding the consumer market every day. Nanotechnology promises to revolutionise
healthcare through innovations in imaging, drug delivery, and 3D tissue scaffolds. A
session on nanobiomaterials addressed challenges in making nanobiomaterials, their
applications and toxicity, a prime concern.
180 Appendix D: Conferences and Workshops

Orthopaedics, one of the foremost branches of medicine, where the use of bioma-
terials has resulted in significant clinical success, has several issues related to pros-
thesis such as plates, screws, and joints primarily made of metallic alloys that are
widely used. There is a need to improve the performance of these medical devices.
Narendra B. Dahotre (University of North Texas, USA) discussed various surface
engineering strategies to achieve appropriate surface morphology and chemistry. It is
being increasingly realised by the biomaterials community that conventional manu-
facturing and materials processing techniques are inadequate to meet the specialised
needs of biomedical application of materials. Thus, novel techniques are required
to synthesise, process, and characterise biomaterials. Extent of osseointegration is
enhanced by providing the desired pore size distribution and pore interconnectivity.
The challenges of working with stem cells and their interactions with biomaterials
were taken into account. Given their pluripotency and self-renewal capacity, stem
cells are likely to be the major cellular sources for different regenerative medical
therapies.

International Conference on Design of Biomaterials

(BIND-06) at IIT Kanpur, December 2006

One of the motivations to organise BIND-06 was to bring together the leading medical
practitioners, biologists, and materials scientists from around the globe to share
their excitements in the emerging area of biomaterials science. The conference was
thus named due to its focus on discussing the frontier areas of new bulk/coating
materials for biomedical applications. Such materials are synthetically produced
outside the human body and once found suitable, are used in human implants.
Therefore, they essentially integrate with the living organs and participate in the
functioning of living systems. Another reason is that the research on biomaterials
essentially ‘binds’ biologists/biotechnologists with engineers (mechanical, chem-
ical, metallurgy)/materials scientists and clinicians (orthopaedic surgeons, dental
surgeons, ophthalmic surgeons, and cardiac surgeons). An appropriate binding of
research ideas/expertise ensures a comprehensive understanding of the processing-
microstructure-properties (physical as well as in vitro/in vivo) of biocompatible
materials.
Among other directions, the conference focused on some topical areas, including
bioceramics, polymeric biomaterials, cell–biomaterial interaction, and tissue engi-
neering. The advances in the areas like tissue engineering, bioceramics, polymeric
biomaterials, orthopaedic biomaterials, cardiovascular biomaterials, nanobiomate-
rials, ophthalmic biomaterials, dental biomaterials, and biomaterial applications were
largely discussed in the symposium. Besides various technical sessions, a panel
discussion on ‘Biomaterials Education, Research and Industries: Future Perspec-
tives’, focused sessions to explore future possibilities of international collaboration
with foreign delegates, were also organised during BIND-06. Two separate poster
Appendix D: Conferences and Workshops 181

sessions were held for students/researchers and a total of 70 abstracts were judged by
an expert panel of five judges (each session) for three best awards in each session. In
addition, two parallel sessions (one on metals and ceramics and other on polymeric
biomaterials and drug delivery), focused on students’ oral presentation, were also
held. These sessions were also judged by a panel of three experts in each session.
More than 250 delegates, including experts from 14 countries, namely Australia,
Belgium, France, India, Japan, Malaysia, Nepal, Portugal, Singapore, Sweden,
Turkey, UK, and USA, participated in BIND-06. In particular, eight invited speakers
from USA delivered Plenary, Keynote and invited talks. The US participants were
drawn from University of Virginia, Rensselaer Polytechnic Institute, Iowa State
University, Columbia University, University of North Texas, University of Texas at
San Antonio, NASA Glenn Research Center, New York University. In addition to 8
invited speakers from USA, the conference had a total of 19 invited speakers, of which
6 were from India and the remaining was from foreign countries, other than USA.
The Indian participants were from institutions like IITs, SCTIMST, NIPER, Insti-
tute of Life Sciences, SASTRA, AIIMS, Reliance Life Sciences, Mumbai, Hindustan
Latex, etc. In addition, top officials from government funding agencies (DST, DRDO,
IUSSSTF) also participated in the conference.
Appendix E
Road-Mapping Meetings

First Meeting of Biomedical Implants Materials Mission

(BIM2 ) Mission at KIHT, 19 November 2018

The Kalam Institute of Health Technology (KIHT), Visakhapatnam, hosted a daylong

partnership meet with key stakeholders of the medical implants industry to explore
solutions to promote indigenous innovation in the critical health technologies. The
meet was held in the premises of Andhra Pradesh MedTech Zone (AMTZ) and
featured an august gathering of experts representing the biomaterial segment of
medical technology. The meet was organised as part of the initiative of KIHT to
promote healthcare innovation needs of the country, and the focus of the meet
was on biological implantable materials, their sourcing, manufacturing, and clinical
applicability in the Indian healthcare context.
Stakeholders represented by various reputed institutions like IITs, NITs, IISc, VIT,
National labs, MSME manufacturers, large-scale manufacturers like Tata Steel New
Materials Business, and policy facilitation units like KIHT and AMTZ, etc. partic-
ipated. The meet presented a forum for active discussion on biomaterial implants
innovations across the country including detailed perspectives of biological mate-
rials and the need to promote more indigenous innovation in the country which could
lead to reduction in India’s import dependency.
KIHT and AMTZ, being the forebearers of the medtech sector, took up the
mandate to facilitate the requisite academic research projects needed to support
manufacturing in a timebound frame and bring together stakeholders to create the
first ever platform for end-to-end biomaterials product realisation. Speaking on the
occasion, Dr. Jitendar Sharma, Managing Director AMTZ, called for closer coop-
eration among academic and industry in the biomaterials sector to address India’s
concerns on import dependency in implantable materials.

© Springer Nature Singapore Pte Ltd. 2020 183

B. Basu, Biomaterials Science and Implants,
https://doi.org/10.1007/978-981-15-6918-0
184 Appendix E: Road-Mapping Meetings

Second Meeting of Biomedical Implants Materials Mission

(BIM2 ) at KIHT, 22 December 2018

The Kalam Institute of Health Technology (KIHT), Visakhapatnam, hosted a daylong

annual review meeting of the Translational Centre of Excellence on Biomaterials for
Orthopaedic and Dental Applications and also a second meeting of the Biomed-
ical Implants and Materials Mission (BIM2 ). This meeting reviewed and promoted
indigenous inventions in the health technology centre across the country. This event
was financially supported by the Department of Biotechnology, Government of India
and the Ceramic and Glass Industry Foundation, American Ceramic Society. The
objective of this meeting was to discuss healthcare innovations in orthopaedic and
dental applications, in particular their related research, manufacturing and clinical
applicability in the Indian healthcare context. This meeting emphasised the detailed
intense knowledge on designs, applicability, compatibility with living systems,
non-contamination attribute, antimicrobial sterilisation needs, etc.
Stakeholders from various reputed institutions like IITs, NITs, IISc, VIT, National
labs, MSME manufacturers, large-scale manufacturers like Tata Steel New Materials
Business, policy facilitation units like KIHT and Andhra Pradesh MedTech Zone
(AMTZ), etc. participated in the meeting. Representatives from Faberz Technology
Pvt. Ltd, Modern Bioceramics Pvt. Ltd and DUCOM Instruments Pvt. Ltd partici-
pated. Mentoring Committee members present were Prof. Abhay Pandit, University
of Ireland, Galway, Mr. Ravi Sarangapani, Smith & Nephew, India, Prof. Surya
Appendix E: Road-Mapping Meetings 185

Kalidindi, Georgia Institute of Technology, Prof. Rajendra Bordia, Clemson Univer-

sity, Prof. H. S. Maiti, Indian Institute of Technology, Kharagpur and Dr. Jitendar
Sharma, Kalam Institute of Health Technology.
This meeting started with opening remarks and a welcome address by Dr. Jitendar
Sharma, Executive Director, MD, AMTZ. KIHT. Further, speaking on the occasion
was Prof. Bikramjit Basu, Professor of the Materials Research Centre, Indian Institute
of Science and Principal Investigator of the Translational Centre of Excellence. Prof.
Basu is currently leading the Academic Consortium of the BIM2 mission. He is also a
Global Ambassador of the American Ceramic Society. Several Centre of Excellence
Mentoring Committee Members and Co-investigators presented their research and
experience in the field of biomedical materials research.

Third Meeting of the Biomedical Implants Materials Mission

(BIM2 ) Mission at IISc Bangalore, 26 February 2019

Representatives from TATA Steel New Materials Business, Kalam Institute of Health
Technology, Intellectual Property and Technology Licensing Cell of IISc and Prof.
Bikramjit Basu attended this meeting, where it was agreed that the key factors for
biomedical products under BIM2 are affordability in the Indian market, indigenous
products and technologies, positive research outcomes, translatable technologies and
acceptance by clinicians. The vision, mission, and objectives were further refined,
as well as funding aspects, the model for the Consortium, running of projects and
legal aspects.
186 Appendix E: Road-Mapping Meetings

Brainstorming Meeting at IIT Delhi and INSA. New Delhi,

26–27 August 2019

The author held a brainstorming meeting to discuss recommendations for this mono-
graph with Prof. Neetu Singh, IIT Delhi, Prof. Shalini Gupta, IIT Delhi, Prof. A. B.
Pandit and Prof. Naresh Bhatnagar, IIT Delhi, on 26–27 August 2019.

Centre of Excellence Meetings: Translational Centre

on Biomaterials for Orthopaedic and Dental applications

Centre of Excellence Review Meeting at IISc, Bangalore, 11

August 2018

Representatives from IISc Bangalore, SCTIMST Thiruvananthapuram, DUCOM,

ANTS Ceramics, KIHT, King George Medical University Lucknow, Georgia Insti-
tute of Technology, VNIT Nagpur, Datta Meghe Institute of Medical Sciences and
TATA Steel New Materials Business attended. Prof. Basu emphasised the importance
of developing a strong cohesive collaboration with KIHT and agreed to provide a
list of innovations to KIHT with assessment of areas for collaboration. Prof. Basu
commented on the market research for the femoral head and that the manufac-
turing cost for the product for the market is Rs 20 crores. Mr. Kingshuk Poddar
suggested that the manufacturing panel of KIHT can assist with this product. Mr.
Poddar commented that the involvement of industry while developing the proto-
type varies—whether it takes on a mentoring role and whether it has a stake during
prototype development. He advised that industry should be involved from Day 1. He
added that there are issues on both sides to be worked out, and that industry should
be involved in meetings with academics so that both sides can come to a common
ground. Dr. Zahir Quaziuddin said that once certification is given for a product, there
should be no problem of acceptance by doctors.

Centre of Excellence Meeting at IISc, Bangalore, 25 July 2017

Representatives from Smith and Nephew met with Prof. Bikramjit Basu and
researchers from IISc. Prof. Basu emphasised the need for creating a bridge between
the work of academic researchers and commercial companies to solve the unmet
needs in the medical field. Dr. Murphy, VP, New Product Development, Smith
and Nephew, proposed to extend their cooperation in the case of solving medical
challenges. Mr. Ravi Sarangapani, Director, New Product Development, Smith and
Nephew mentioned that the biggest paradigm shift in this field of medical research
Appendix E: Road-Mapping Meetings 187

would be the development of regenerative cartilage and that would allow surpassing
of most challenges faced by the use of implants.

Centre of Excellence Second Review Meeting at IISc,

Bangalore, 20 December 2016

In this meeting, there were representatives from SCTIMST Thiruvananthapuram,

CGCRI Kolkata, IISc Bangalore, MSRDC Bangalore, IIEST Shibpur, and CIPET
Chennai. Ms. Mala Srivastava from Nextvel Consulting LLP spoke on the regu-
latory policy status for Medical Devices in the backdrop of the US-FDA and that
of Europe. It was suggested to follow universally accepted ‘Standard Protocols’ to
achieve greater reliability and reproducibility of data. Credible correlation of data
generated from different laboratories and institutes is essential. All projects under
COE need to be executed in a GLP/GMP compliant manner. The need to under-
stand the regulatory issues and requirements along the pathway of translation was
emphasised.

Centre of Excellence Meeting on Biomaterials at IIEST,

Kolkata, 18 December 2015

In this meeting, several aspects of the COE were refined, such as details of the
Mentoring Committee, review meetings, and monitoring of projects. Prof. Bikramjit
Basu, Prof. Abhay Pandit, Prof. Brian Derby, and IIEST researchers were present. It
was decided that a special session on entrepreneurship will be organised alongside the
review meetings. Also, MoU, Confidentiality, IP transfer among partner organisations
are to be established. It was suggested to have an exchange of manpower among the
participating institutes to facilitate training of young researchers.
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