REGENERATIVE ENDODONTICS

Victor Pinheiro Feitosa, DDS,

MSc, PhD, Dental Pulp
Mara Natiere Gonçalves Mota,
DDS, Lorena Vasconcelos Vieira, Autotransplantation: A New
DDS, MSc, Diego Martins de
Paula, DDS, MSc, PhD, Modality of Endodontic
Lívia Lisboa Ribeiro Gomes, DDS,
Luzia Kelly Rios Solheiro, DDS,
Manoel Asciton de Aguiar Neto,
Regenerative Therapy—
DDS, Diego Armando Leite
Carvalho, DDS, and
Follow-Up of 3 Clinical Cases
Francisbe ^nia Alves Silvestre

ABSTRACT
SIGNIFICANCE
The aim of this study was to develop a novel method of endodontic therapy, which we refer to
This study paves the way for as dental pulp autotransplantation. Three patients (2 males and 1 female) were selected for
clinical endodontic endodontic treatment of a uniradicular premolar and extraction of a third molar (without
regenerative therapy by means odontosection). Electric assessment of pulp vitality and computed tomographic imaging were
of pulp autotransplantation undertaken followed by endodontic access and instrumentation using triantibiotic solution for
from an extracted third molar irrigation in the host tooth. A few minutes before the transplant procedure, the third molar was
to a further tooth requiring root extracted, the tooth was sectioned with a diamond blade in a low-speed handpiece, and the
canal treatment in the same pulp was carefully removed. After premolar instrumentation, the harvested and preserved
patient. pulp tissue was reinserted into the root canal followed by direct pulp capping performed using
Biodentine (Septodont, Saint-Maur-des-Fosse
s, France), a liner of resin-modified glass
ionomer cement and composite resin restoration. The teeth were followed up for at least
12 months after the procedures and were analyzed using computed tomographic imaging,
electric pulp vitality testing, and Doppler ultrasound examination. At the 3- and 6-month
follow-ups, positive pulp vitality and regression of periapical lesions were verified. After 9–
12 months, all teeth were revascularized as determined by Doppler imaging, and the tooth
vitality was reestablished with no signs of endodontic/periodontal radiolucency or
complications. Within the limitations of the study, considering that it was a case series with
only 3 patients, we described a highly innovative procedure of pulp autotransplantation, which
appears to be feasible, highlighting the potential for clinical application of pulp regeneration
using this new modality of endodontic therapy. (J Endod 2021;47:1402–1408.)

KEY WORDS
Pulp; regeneration; transplant

Restorative dentistry and endodontics are trending toward a regenerative approach for the pulp/dentin
complex, particularly after the recent advances on mesenchymal stem cell–based tissue engineering
technologies1. Indeed, several animal models have been developed comprising different strategies to
From the Paulo Picanço School of

, Brazil induce pulp regeneration and reconstruction in full length2,3. In order to aid the regeneration process,
Dentistry, Fortaleza, Ceara
growth factors, cytokines, and several microenvironments were introduced2,4,5. However, little of these
Address requests for reprints to Prof
technologies actually reached the clinical case series.
Victor Pinheiro Feitosa, Research Division,
Paulo Picanço School of Dentistry, 900 For the clinical scenario, pulp revascularization of immature teeth affords a threshold for the survey
Joaquim Sa
Street, Fortaleza, Ceara

, of novel regenerative insights6. Recently, a clinical trial7 compared induced bleeding with platelet-rich
Brazil 60135-218. fibrin and platelet-rich plasma for open apex necrotic teeth. Moreover, other clinical case series8,9 have
E-mail address: victorpfeitosa@hotmail. shown the use of platelet-rich fibrin to achieve pulp regeneration with reasonable outcomes.
com
0099-2399/$ - see front matter
Nevertheless, animal studies10 revealed a lack of generation of proper sound pulp tissue by means of
platelet concentrates, which rather form bonelike tissue in the root canal. A further strategy to attain
Copyright © 2021 American Association
of Endodontists.
successful pulp regeneration in the clinical outlook is the transplant of dental pulp stem cells (DPSCs)
https://doi.org/10.1016/ harvested from teeth requiring root canal treatment diagnosed with irreversible pulpitis11. Such cells were
j.joen.2021.06.014 expanded in vitro before transplantation to the host teeth. More recently12, seeded minced pulp

1402 Feitosa et al. JOE  Volume 47, Number 9, September 2021

mesenchymal stem cells achieved fast extraction without odontosection and without rotary files (WaveOne Gold; Dentsply Sirona,
replication and odontogenic differentiation with the presence of a carious cavity. York, PA) with irrigation using triantibiotic
noteworthy potential for clinical application. Initial panoramic radiography (Fig. 1A– solution (ciprofloxacin, minocycline, and
The transplantation of the entire pulp C) and computed tomographic imaging of the metronidazole)13,14. Before the rotary files, 1
might yield the optimal “scaffold” for the tooth requiring root canal treatment were #10 manual K-file (Dentsply Sirona) was used
differentiation of DPSCs in their natural performed. All teeth were diagnosed with pulp to perform the patency. No apical bleeding
environment. Furthermore, most nerves and necrosis depicting periapical radiolucency. was performed because the clinical protocol
blood vessels are formed, thereby facilitating Third molar extraction was undertaken without was not similar to revascularization15.
the revascularization and connective process odontosectioning and with minimal injury to the The residue of irrigating solution was
of transplanted pulp. Altogether, this modality tooth after local anesthesia using 1.8 mL 2% thoroughly washed with sterile saline solution.
of the pulp regeneration technique could be lidocaine (1:100,000 epinephrine) with the EDTA at 17% concentration for 5 minutes was
obtained in clinical procedures without the nerve block technique. The extracted teeth used for the dentin conditioning protocol16.
need for in vitro DPSC laboratorial expansion. were briefly stored in sterilized saline solution, This solution was twice rinsed with sterilized
Dental pulp autotransplantation of pulp and the site was sutured. The premolars saline solution, and the root canal was slightly
harvested from a third molar requiring requiring root canal treatment were dried with an absorbent paper cone.
extraction to a host tooth needing root canal anesthetized as mentioned previously and Meanwhile, the extracted third molar was
treatment may aggregate a clinically feasible isolated with a rubber dam, and pulp chamber initially cut with a small diamond saw in a low-
procedure with striking potential for true pulp access was executed with diamond burs in a speed handpiece (Fig. 2A) running water
regeneration, avoiding body rejection and high-speed handpiece under running water washing with sterilized saline solution. This first
inflammation. However, to the best of our after caries or defective restoration removal. cut penetrated only 1–2 mm around the entire
knowledge, dental pulp autotransplantation Canal instrumentation was undertaken using mesial and distal surfaces and 3–4 mm on the
has not been investigated thus far.
Therefore, this case series aimed to
describe the clinical procedures for dental pulp
autotransplantation and to conduct a clinical
follow-up for at least 9 months of 3 patients
treated with this modality of regenerative
endodontic treatment. Despite being a
promising technique, there are still some
points to be improved, such as the time in
which the pulp remains with its vital cells to
reconnect after extractions. The issue to be
considered is that the pulps need to be
removed only from vital teeth that have not
suffered any type of trauma before, during, or
after the extractions for the sake of a better
autotransplantation prognosis.

MATERIALS AND METHODS

Three patients with a need for root canal
treatment in a single-rooted premolar and third
molar extraction were recruited from the Dental
Clinics of Paulo Picanço School of Dentistry,
Fortaleza, Ceara
, Brazil. The protocol and
project were evaluated and approved by the
institutional ethics committee (protocol
3585776). All patients discussed the treatment
options and signed informed consent forms
that explained the aim of the study and the
potential complications; they conformed with
the clinical/radiographic follow-up periods of 1,
3, 6, 9, and 12 months. The inclusion criteria
were patients 18–40 years old with no sex
predilection and irreversible pulpitis or pulp
necrosis signs with spontaneous pain or
periapical radiolucency in single-rooted tooth,
thereby requiring root canal treatment, with a
periodontal pocket depth ,3 mm. The
presence of tooth discoloration was not an FIGURE 1 – (A–C ) Panoramic radiographs of the initial visit of 3 patients. The black circles indicate the tooth requiring
exclusion criterion. Furthermore, the patients root canal treatment (receptor tooth), whereas the asterisks indicate the third molars planned for extraction (pulp donator
needed to possess a third molar prone to tooth). (A ) Patient 1, (B ) patient 2, and (C ) patient 3.

JOE  Volume 47, Number 9, September 2021 Dental Pulp Autotransplantation 1403
 etching technique with 37% phosphoric acid
gel (Condac 37; FGM, Joinville, Brazil) only at
the enamel borders for 15 seconds, which was
rinsed with distilled water for 30 seconds. Both
dentin and enamel were air-dried for 30
seconds before the active application of primer
for 20 seconds with a slight air blast to
evaporate solvent and active application of
adhesive for 20 seconds. Bonding agent light
curing was performed for 40 seconds with the
Valo LED unit. Resin composite restoration
was incrementally built with 2-mm-thick
increments (Opallis, FGM) individually light
cured for 20 seconds. After the occlusal
check/adjustments, the patient went home
with pharmacologic receipt of 600-mg
ibuprofen pills to be taken every 8 hours for
3 days. No antibiotics were prescribed for any
patient. Receptor teeth underwent computed
tomographic imaging at this first clinical visit
(Fig. 3A1–3C1). Patients were scheduled for
follow-up return visits every 3 months after the
autotransplantation clinical procedure. At each
return visit, they were evaluated by computed
tomographic imaging (at 6 and 12 months) or
periapical radiography (at 3 and 9 months),
electric pulp vitality testing (Pulp Tester Digital;
Odous de Deus, Belo Horizonte, Brazil),
occlusal check/adjustments of restorations,
and Doppler ultrasonic imaging (only at the 1-
year follow-up). Patients were warned that in
case of unsuccessful autotransplantation, the
transplanted pulp would be removed, and
traditional endodontic treatment would be
performed by filling the canal with gutta-percha
and endodontic sealer.

RESULTS
The 3 patients reported no symptoms within
the first 3 months after the procedures. At the
FIGURE 2 – The method for minimally invasive pulp removal and insertion toward pulp transplantation. (A ) The initial 3-month follow-up, all patients reported slight
mesiodistal cut of the donator tooth with a small diamond disc in a low-speed handpiece to create a notch around the twinges at the periapical region of the receptor
entire surface of the tooth, which is the triggering zone to break the tooth into 2 parts. The notch was forced with a tooth, which started after 40 days and
syndesmotome, and the tooth was fractured to expose the pulp. (B ) The fractured tooth after careful removal of the pulp occurred during the initial 2–3 months after the
with small tweezers. (C ) The careful insertion of the harvested pulp with the aid of a gutta-percha cone inside the procedure. No response to electric pulp vitality
previously cleaned and instrumented root canal at the receptor tooth. testing was detected at the 3-month follow-up.
The patients depicted a reduction of periapical
radiolucency as highlighted in computed
occlusal surface of the molar in order to create calcium silicate cement, which was tomographic imaging at the 6-month follow-up
a notch without touching the pulp tissue. The manipulated according to the manufacturer’s (Fig. 3A2–3C2) of the teeth submitted to the
notch was pressed with a sharp straight instructions. After 10 minutes to allow autotransplantation procedure. Moreover, the
syndesmotome to section the teeth into 2 complete setting of Biodentine, resin-modified electric pulp vitality tests resulted in a positive
halves, allowing careful pulp removal with small glass ionomer cement (Riva Light-Cure; SDI, vitality response with similar amperage to
tweezers (Fig. 2B). Pulp tissue (from donator Bayswater, Australia) was applied as a liner those of intact teeth from the same patient.
tooth) was inserted into the root canal of the and light cured for 20 seconds with an LED After 1 year from autotransplantation,
receptor tooth with the aid of disinfected gutta- Valo unit (1200 mW/cm2; Ultradent, South complete regression of periapical lesions was
percha cones (Fig. 2C) to avoid damaging the Jordan, UT) to avoid a negative reaction verified for patients 1 (Fig. 3A3) and 2
tissue. between Biodentine and adhesive (Fig. 3B3), whereas the radiolucency in patient
Direct pulp capping was performed in restoration17. The 2-step self-etch adhesive 3 was almost entirely diminished (Fig. 3C3).
the receptor tooth using Biodentine Clearfil SE Bond (Kuraray Medical, Kurashiki, Positive pulp vitality was confirmed, and
(Septodont, Saint-Maur-des-Foss
es, France) Japan) was applied using a selective enamel revascularization was further proved by

1404 Feitosa et al. JOE  Volume 47, Number 9, September 2021

FIGURE 3 – Computed tomographic images of teeth receiving pulp autotransplantation. A1–A3 are related to the first patient’s lower second premolar, which (A1 ) depicted periapical
radiolucency initially, (A2 ) was notably reduced at the 6-month follow-up, and (A3 ) disappeared after 1 year of the treatment. (B1–B3 ) The same trend occurred in patient 2 as well as
in patient 3, with (C1–C3 ) a striking reduction of periapical lesions over time, although the 1-year period was not enough to demonstrate total absence of periapical radiolucency. At the
1-year follow-up, all teeth showed positive pulpal vitality in the electric test.

Doppler imaging (Fig. 4) at the periapical region simulation of a clinical scenario18. Even and previously built vascularization. Indeed,
of each tooth subjected to the pulp allogeneic tooth transplantation of the entire these factors may enhance the success of pulp
autotransplantation procedure. No signs of tooth from the daughter to the mother was regeneration treatments and the strategy12,
endodontic/periodontal complications were successfully demonstrated with the support of which used minced pulp as a source of
observed for all patients at the 1-year follow- 3-dimensional printing in order to achieve an mesenchymal stem cells in order to provide
up. The 3 cases are still being monitored. optimal clinical outcome19. These clinical odontogenic differentiation with high potential
procedures triggered the concept and idea of for protein and alkaline phosphatase
the present report by means of using the tissue expression. Furthermore, in vivo clinical
DISCUSSION from an extracted third molar to replace a regeneration of pulp tissue would be faster
Entire tooth autotransplantation of the third defective tissue in a further area of the oral than using only scaffolds, mesenchymal stem
molar is a well-known and established environment. cells, and growth factors once all structures
procedure for the replacement of defective Several advantages are included when are already formed.
molars requiring extraction in modern clinical performing pulp tissue autotransplantation, For a successful clinical procedure of
dentistry. More recently, 3-dimensional such as a lack of transplant rejection, the same pulp autotransplantation, the extraction of a
printing technology aided such a procedure by DNA and RNA in all cells, completely mature third molar needs to occur with minimal
allowing the training of operators and the connective tissue, a formed neuronal network, damage to the tooth, and tooth sectioning

JOE  Volume 47, Number 9, September 2021 Dental Pulp Autotransplantation 1405
FIGURE 4 – Doppler ultrasonic assessment of periapical revascularization in teeth subjected to pulp autotransplantation. (A1 and A2 ) Patient 1 and (C1 and C2 ) patient 3
demonstrated high blood flux. The blood flux of (B1 and B2 ) patient 2 was slightly lower than other patients (1 and 2) but was detected and positive in both arterial and venous
directions.

cannot be used, excluding the possibility of irrigant, thereby diminishing the possibility of platelet-rich fibrin9. Nevertheless, these
using teeth that are not well positioned. Herein, tooth staining. Another traditional procedure treatments require laboratory processes to
the third molars extracted (asterisks in Fig. 1) commonly performed is the final irrigation with obtain platelet concentrates or stem cell
were likely to be extracted with minimal injury 17% EDTA16 before tissue transplantation. By expansion/replication20. Herein, no laboratory
because they were vertically inclined. Besides, opening dentinal tubules and conditioning intervention is demanded for pulp
the tooth must be stored for the shortest superficial dentin, several growth factors are autotransplantation, which represents a
period in sterilized saline solution once released such as brain-derived neurotrophic significant benefit in comparison with previous
complete disinfection before pulp removal and and growth/differentiation factor 158. clinical strategies. In other words, pulp
transplantation is mandatory20. The section of Particularly, these neuronal growth factors autotransplantation as highlighted in the
the extracted tooth is undertaken only after participated in the regeneration process of present report is entirely performed in a
root canal instrumentation in the receptor transplanted pulp in order to obtain vitality clinical dental office without the need for
tooth, and the entire process demands a regain25. further experiments outside the office.
sterilized handpiece, diamond disc, and gloves Concerning the few clinical studies In the clinical steps of the present case
(Fig. 2A). Pulp removal is also removed with about actual pulp regeneration, the majority series, pulp capping after autotransplantation
sterilized tweezers (Fig. 2B) and inserted dealt with teeth diagnosed with irreversible was performed with the gold standard calcium
sterilized gutta-percha cones (Fig. 2C). pulpitis8,9,11. With initial conditions depicting silicate cement (Biodentine), which attains the
Altogether, such care might promote minimal the absence of periapical radiolucency, the optimal pulpal response yielding the release of
contamination during the process, thereby optimal vascularization and lack of odontogenic growth factors, alkaline
increasing the likelihood for bacterial-free inflammatory mediators in bone may facilitate phosphatase release, and dentin bridge
endodontic regeneration. the revascularization and reinnervation of formation9,25. Afterward, resin-modified glass
In this regard, root canal instrumentation transplanted tissue/cells. Conversely, in the ionomer cement was applied, and the gold
and irrigation were performed using rotary files present clinical cases, all 3 patients presented standard26 2-step self-etch adhesive Clearfil
and triantibiotic solution21, respectively. periapical radiolucency at the initial condition SE Bond was used with the selective enamel
Although a recent report22 suggests (Fig. 3A1–3C1), which may possess lower etching technique27 in order to afford optimal
clindamycin is less cytotoxic and promotes blood irrigation and likely bacterial sealing of the transplanted pulp and cavity
higher angiogenic potential than minocycline, contamination. These factors diminish the margins. In fact, these procedures for pulp
the present case series employed the traditional feasibility of the treatment. However, capping might play an important role on the
solution used for revascularization procedures. successful outcomes were attained in a clinical long-term outcome of the
Another drug feasible to replace minocycline relatively short period, also achieving a autotransplanted pulps.
would be doxycycline23, which is approved by reduction of periapical lesions (Fig. 3). To confirm apical revascularization, the
the US Food and Drug Administration and does Autologous mixtures were proposed 3 patients underwent Doppler ultrasonic
not induce tooth staining due to oxidation over for transplantation to the root canal for the evaluation (Fig. 4A1–C2), which confirmed
time24. However, doxycycline was rarely sake of endodontic regeneration, such as blood perfusion with a characteristic pulse
investigated in pulp regeneration studies, and minced pulp12, extracted/expanded image (Fig. 4A1–4A3), thereby proving
the triantibiotic solution was used only as DPSCs11, platelet-rich fibrin8, and leukocyte revascularization. This report is the threshold

1406 Feitosa et al. JOE  Volume 47, Number 9, September 2021

for the autotransplantation of pulp and likely and sizes of root canals. Future studies ACKNOWLEDGMENTS
the application of allogeneic pulp should focus on the possible assessment of
The authors thank Dr David Araujo for the
transplantation within relatives. The main pulp transplantation among people from
Doppler ultrasonic surveys.
limitations of the present treatment protocol different families and a feasible test to confirm
Supported by the Brazilian Ministry of
rely on patients without the presence of third the gene compatibility for such a novel sort of
Education (Coordenaç~ao de Aperfeiçoamento
molars prone to pulp donation or in cases with transplantation procedure. Because the
de Pessoal do Nível Superior grant
teeth possessing an abscess or purulence or present report is a series of clinical cases,
23038.006958/2014-96, Principal Investigator
even when the third molars require there is a limitation concerning the small
Victor Pinheiro Feitosa).
odontosection. Indeed, the clinical procedure sample size. Therefore, further studies should
The authors deny any conflicts of
should be improved, surveying the most focus on a higher number of patients in a
interest related to this study.
suitable irrigation protocols and antibiotics, randomized clinical trial setup because it is a
the optimal root canal instrumentation, and promising procedure when you have the
the digitalization of the process in order to conditions suitable to perform
ease the fitting of pulps into different shapes autotransplantation.

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