Front. Mater. Sci.

China 2010, 4(1): 29–33

DOI 10.1007/s11706-010-0009-0

REVIEW ARTICLE

Electrospun nanofibers: Work for medicine?

Susan LIAO (✉), Casey K. CHAN, S. RAMAKRISHNA

Healthcare and Energy Materials Laboratory, Department of Mechanical Engineering, Faculty of Engineering,
National University of Singapore, Singapore 117576, Singapore

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Abstract Attempts have been made to fabricate nanofi- wide range of specialized cell types. However, stem
brous scaffolds to mimic the chemical composition and cells in and by themselves will not be sufficient for most
structural properties of the extracellular matrix (ECM) for therapies. Unconditioned stem cells with non-specific
tissue/organ replacement. Nanofiber scaffolds with various targeting have two disadvantages, namely, a large number
patterns have been successfully produced from synthetic of cells for initial implant may be required, and the result
and natural polymers through a relatively simple technique maybe unpredictable. The clinical potential of stem cell
of electrospinning. The resulting patterns can mimic some based therapies will be fully realized by providing
of the diverse tissue-specific orientation and three-dimen- support for these cells following implantation into the
sional (3D) fibrous structures. Studies on cell-nanofiber patient [1]. The support is not only to facilitate stem cell
interactions, including studies on stem cells, have revealed proliferation but also to provide a functional environment
the importance of nanotopography on cell adhesion, to improve stem cell quality. The ideal support for the stem
proliferation and differentiation. Furthermore, clinical cell should be a natural extracellular matrix (ECM)-like
application of electrospun nanofibers including wound niche with a variety of controllable cues, just as intended
healing, tissue regeneration, drug delivery and stem cell by nature.
therapy are highly feasible due to the ease and flexibility of
fabrication of making nanofiber with this cost-effective
method using electrospinning. In this review, we have 2 Biomimetic nanomaterials by
highlighted the current state of the art and provided future electrospinning
perspectives on electrospun nanofiber in medical applica-
tions. Structurally, natural ECM consists of a variety of protein
fibrils and fibers interwoven within a hydrated network of
Keywords biomimetic materials, nanofiber, electrospin- glycosaminoglycan chains. The nanoscale structure of the
ning, stem cell, medicine ECM is a natural assembly of intricate nanofibers for cell
support and presents an instructive background to guide
cell behavior [2–4]. Typically, cells respond to environ-
1 Introduction mental features of all scales from the macro down to the
molecular scale. The functional cues presented by the
Recent research on stem cells and regenerative medicine ECM can be chemical in nature, such as the presence of
offers huge opportunities for developing new therapeutic adhesive proteins, or purely physical, such as topography
approaches to treat life-threatening diseases associated from nanometer to micrometer scales of the ECM, or by
with aging and accidents such as Parkinson’s disease, the transfer of mechanical and electrical stimuli from the
diabetes, cardiovascular disease, cancer, and critical size external environment [5]. Cells will lay down a new matrix
defects of human tissues. The stem cell has been and secrete small biomolecules to maintain a dynamic
recognized as a promising alternative to somatic cells in “give and take” relationship between the ECM and cells.
the application of cell therapy owing to its self-renewal The ECM may provide a protective environment for the
potential through cell division and differentiation into a living cells under a harsh transportation environment. For
example, tissue-engineered grafts were successfully
implanted after air transportation for 20 to 46 h without
Received November 20, 2009; accepted December 8, 2009 temperature and oxygenation control [6]. In wound healing
E-mail: [email protected] and embryogenesis, the ECM is formed by a direct
30 Front. Mater. Sci. China 2010, 4(1): 29–33

hierarchical assembly process through interaction with the interactions at both the cellular [8] and tissue/organ level.
regenerating cells. It would therefore be advantageous to It encompasses the collective behaviors of interacting
create a scaffold that will mimic some of the structural nanoscale components, where scale and complexity lead
properties, such as the nanotopography of natural ECM to ‘entirely new properties’. The question then is how
[7,8]. these materials should be organized into ensembles that
The idea of designing biomimetic nanomaterials that can direct assembly of systems of nanoscale components that
actively direct the behavior of cells to facilitate the would be capable of assuming cell-ECM organization [8].
regeneration of tissues and organs has been widely Nanomaterials, produced mostly by synthetic bottom-up
explored in recent years [9]. Much of the early effort in methods, are discontinuous objects, and this leads to
nanoscience and nanotechnology has focused on the difficulties with their alignment, assembly, and processing
synthesis and characterization of individual or homoge- into applications. Electrospinning technology enables
neous arrays of nanoscale elements. It is desirable, based production of long and continuous nanofibers from
on an understanding of synthetic biology, to fabricate a polymer solutions in high electric fields, and was utilized
scaffold with a combination of nanoscale elements that to fabricate fabric products in the early 1930s [10]. The
has a complexity that would allow for effective nanofibers can be routinely prepared from a variety of

Fig. 1 Electrospun nanofibers with various morphologies and assembled patterns (adapted from our results and Ref. [14])
 Susan LIAO et al. Electrospun nanofibers: Work for medicine? 31

natural and synthetic polymers, as well as composites acid) (PLGA)/collagen nanofibers, after being coated
containing inorganic solids such as nano-hydroxyapatite, with E-selectin, can capture the 67.41% HSCs within 30
the major component of bone tissue. The nanofibers can min at room temperature. Over 50% percent of the MSC
also be conveniently functionalized by encapsulation or population adhered to the electrospun collagen nanofibers
attachment of bioactive species such as proteins, enzymes, after 30 min at room temperature. The capture efficiency
DNA and growth factors to control proliferation and was increased to over 70% when the collagen nanofibers
differentiation of cells seeded on the scaffolds [11,12]. were pre-coated with monoclonal antibodies which
Townsend-Nicholson et al. demonstrated the feasibility of recognize CD29 or CD49a that would bind to stem cells
using coaxial spinning technology for biological and [18]. Increasing HSC numbers ex vivo would be of great
biomedical applications including the deposition of living benefit for transplantation purposes or genetic modifica-
cells as composite threads for forming active biological tion, as expanding the HSCs in vivo or in vitro remains to
scaffolds [13]. Cell viability throughout the process be the bottleneck in clinical applications of HSCs, and
remained high, with approximately (67.61.9)% cells particularly in cord blood transplantation [19]. Recent
surviving the electrospinning process as compared to studies also suggest that covalently immobilized adhesion
(70.65.0)% for control cells. Moreover, the electrospin- peptides and fibronectin on substrates, especially on
ning process has unique potential for cost-effective electrospun fibers, can significantly influence the proli-
control of fiber placement and integrated manufactur- feration characteristics of cultured HSCs [20–23]. A
ing of two- and three-dimensional nanofiber assemblies, nanofibrous structure of synthetic polyamide matrix
as shown in Fig. 1 [14]. The nanofiber assemblies (Ultra-WebTM) has been used to culture embryonic stem
typically have very high open porosity in combination with cells (ESCs) to maintain their “stemness” properties [24].
large surface areas [15]. Other characteristics, including The ESC/nanofiber cultures have significantly larger
ease of processing and tailorable mechanical properties, colonies of undifferentiated cells and enhanced prolifera-
size, and shape of the fibers [7], make electrospinning tion compared with controls cultured on glass coverslips
suitable for industrial applications in addition to laboratory and similar polymer films, suggesting that the physical
use. cues from the unique geometry of nanofibrous surfaces
regulate cellular activities. MSCs from the bone marrow
maintained in poly(ε-caprolactone) (PCL) nanofibrous
3 Stem cells on electrospun scaffolds scaffolds differentiate along adipogenic, chondrogenic, or
osteogenic lineages [25,26]. These electrospun polymers
Our recent data showed that hematopoietic stem cells produce an interconnected porous matrix capable of
(HSCs) [16] as well as mesenchymal stem cells (MSCs) encouraging significant cell proliferation and cell-cell
[17] can rapidly and effectively attach to functionalized interactions in both MSCs and mouse ESCs [27]. Xin et
electrospun nanofibers. Blended poly(lactic-co-glycolic al. confirmed that PLGA nanofibers can accommodate the

Table 1 Electrospun nanofibers in current (C) clinical procedures

No. Name Applications Owner Remarks
C1 Nanofiber Bandages Clinical trials for leishmaniasis in
(nanobandage) Univ. of Akron, chemistry (Prof.
Columbia, South America. Highly
Daniel Smith and Prof. Darrell Phase II clinical trials.
absorbent bandages would slowly
Reneker)
release drugs (nitric oxide) to a wound.
C2 Nanomesh STAR Inc., a startup at the State Uni-
Anti-adhesion: surgical adhesions–
versity of New York, Stony Phase II clinical trials.
scar tissue
Brook (Prof. Benjamin Chu)

Table 2 Electrospun nanofibers in potential (P) clinical procedures

No. Name Applications Remarks
P1 Nanofiber tube Long term SMCs-nanofiber tube construct has been reached by
Vascular graft/nerve graft with growth co-culture up to 3-mons. Aligned nanofiber has been found to
factors guide neuron growth effectively based on in vitro and in vitro
studies.
P2 Nanofiber mesh Full thickness skin repair with cells Unique cell-nanofiber interaction at wet-dry environment.
P3 Nanofiber/hydrogel Cartilage repair/other soft tissue repair Pattern cells within the scaffold.
P4 Nanofiber based composite Bone repair or osteochondral graft With similar composition and hierarchical structure to native bone.
P5 Nanofiber mesh Cell sorting/supporting system, cell sheet HSC/ESC/MSC on functionalized nanofiber.
carrier
P6 Core-shell Nanofiber Drug delivery system Controllable drug release.
32 Front. Mater. Sci. China 2010, 4(1): 29–33

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