Curr Oral Health Rep (2016) 3:293–301
DOI 10.1007/s40496-016-0109-8
ORODENTAL REGENERATIVE MEDICINE (M BARTOLD, SECTION EDITOR)
Current Developments in Regenerative Endodontics
Sahng G. Kim 1 & Bill Kahler 2 & Louis M. Lin 3
Published online: 1 September 2016
# Springer International Publishing AG 2016
Abstract This review outlines the biological basis and
clinical protocols used currently in regenerative endodontic
procedures and discusses future directions in pulp regene-
ration appraches. Since the discovery of dental stem cells
capable of differentiating into odontoblast-like cells and
revascularization/regenerative endodontic therapy with the
potential of promoting thickening of the canal walls and con-
tinued root development of immature permanent teeth with
necrotic pulps, the study of pulp tissue engineering or pulp
tissue regeneration has taken a giant step forward in biological
and clinical endodontics. The biological concept of regenera-
tive endodontics involves the triad of stem cells, scaffold, and
signaling molecules. In preclinical studies, researchers are
looking for mesenchymal stem cells not only capable of
differentiating into odontoblast-like cells but also highly
angiogenic/vasculogenic and neurogenic for complete pulp re-
generation. Tremendous efforts are also dedicated to search for
three-dimensional biomimetic scaffolds to enhance stem cell
migration, adhesion, proliferation, and differentiation as well
This article is part of the Topical Collection on Orodental Regenerative
Medicine
* Louis M. Lin
lml7@nyu.edu
Sahng G. Kim
sgk2114@cumc.columbia.edu
Bill Kahler
w.kahler@uq.edu.au
1
Division of Endodontics, College of Dental Medicine, Columbia
University, New York, NY 10032, USA
2
School of Dentistry, University of Queensland, Brisbane, Australia
3
Department of Endodontics, College of Dentistry, New York
University, 345 East 24th Street, New York, NY 10010, USA
as tissue structure support. In clinical trials, besides immature
permanent teeth with necrotic pulp, regenerative endodontic
therapy has been employed to treat mature permanent teeth
with necrotic pulps, teeth with persistent apical periodontitis
after primary root canal therapy, and traumatized teeth asso-
ciated horizontal root fractures, root resorption, and avulsion.
Keywords Dental stem cells . Immature teeth . Necrotic
pulps . Pulp tissue regeneration . Regenerative endodontics .
Revascularization
Introduction
What Is Regenerative Endodontics?
Regenerative endodontics is the scientific study of the biolo-
gical process of regenerating or engineering human dental tis-
sues within and around the root canals to restore normal func-
tion. The ultimate goal of regenerative endodontic treatment is
to retain natural dentition through healing apical periodontitis
and restoring the functional integrity of the pulp-dentin com-
plex. From a clinical perspective, regenerative endodontic pro-
cedures may provide a tooth with a longer life span by curing
and preventing apical periodontitis. From a biological perspec-
tive, these procedures may allow a tooth to regain the essential
physiological functions such as immune defense and tissue
homeostasis. Since the American Dental Association adopted
Bpulpal regeneration^ as a treatment modality in 2011 [1],
regenerative endodontics has gained increasing attention in
providing a biologically based treatment and promoting root
maturation in immature necrotic teeth. Furthermore, the
findings from preclinical studies using tissue-engineering stra-
tegies have suggested that the regenerative endodontic proce-
dures also can be performed in mature teeth [2–4].
294
Nygaard-Östby conducted the pioneering work in the field
of regenerative endodontics in 1961 [5]. This study demon-
strated that fibrous connective tissue and mineralized tissue
formed in the root canals of mature teeth after mechanical root
canal debridement and formaldehyde medication for necrotic
teeth evoked bleeding into the root canals followed by filling
the canals with gutta percha and Kloroperka NO paste short of
root apices [5]. In a study by Rule and Winter in 1966,
polyantibiotic pastes consisting of neomycin sulfate, poly-
myxin B sulfate, bacitracin, and nystatin were first used as
intracanal medicaments to disinfect the root canals and pro-
mote continued root formation in immature necrotic teeth [6].
Iwaya and colleagues in 2001 described regenerative end-
odontic treatment of an immature necrotic premolar with dens
evaginatus [7]. They reported successful treatment outcomes
including the resolution of clinical signs and symptoms,
healing of apical periodontitis, continued root development,
and return of tooth vitality. Banchs and Trope in 2004 dem-
onstrated a similarly successful clinical case using a more
controlled clinical protocol, which established guidelines used
by many studies of current regenerative endodontic proce-
dures [8].
Biological Concept of Regenerative Endodontics
According to a concept of tissue engineering proposed by
Langer and Vacanti in 1993, three essential elements —cells,
matrices, and tissue-inducing substances—are required to en-
gineer or regenerate a tissue [9]. They are presently called the
triad of tissue engineering—stem cells, scaffolds, and signal-
ing molecules, which also function as the biological concept
of regenerative endodontics. A patent blood supply is also
crucial for the continuity of the regenerative processes.
Stem Cells
Among the triad of tissue engineering, stem cells are consid-
ered the centerpiece of tissue regeneration. Stem cells with the
characteristics of self-renewal and differentiation into multiple
cell lineages can participate in the regenerative process by
being part of regenerated tissues and/or releasing trophic fac-
tors to modulate the cellular activities in the surrounding tis-
sues [10–14]. Dental pulp stem cells [11], stem cells of apical
papilla (SCAP) [15, 16], stem cells from human exfoliated
deciduous teeth [17], and stem/progenitor cells from inflamed
human dental pulp [18] are thought to be the main cell sources
for pulp and dentin regeneration. The periapical stem/
progenitor cells are mobilized into the root canal space by
induced bleeding or appropriate biological chemotactic fac-
tors before they differentiate into the specific cell lineages
and construct the tissues in the root canals. Exogenous stem
cells isolated from various sources such as dental pulp, bone
Curr Oral Health Rep (2016) 3:293–301
marrow, and adipose tissue have been used in preclinical an-
imal models not only to regenerate the pulp-dentin complex
but also to study the fate of transplanted cells by in vivo cell
lineage tracing [3, 4, 19].
Scaffolds
Scaffolds are three-dimensional physical structures, which
provide structural and biological supports for cellular activi-
ties such as attachment, proliferation, differentiation, and ap-
optosis and allow for exchange of gases, nutrients, and meta-
bolic products during the regenerative process [20]. The scaf-
fold materials should have biocompatibility and biodegrad-
ability that allow controlled release of biological cues [20,
21]. Ideally, they should have material properties that mimic
the target tissues and chemical properties that promote the cell
adhesion, proliferation, and differentiation [21]. Natural poly-
mers such as collagen [22], hyaluronic acid [23], and alginate
[24] or synthetic materials such as polylactic acid [25] and
poly lactic co-glycolic acid [26] have been used in preclinical
studies for pulp and dentin regeneration. When a material is
selected as a scaffold for pulp regeneration, the degradation
time of the material needs to be considered because the scaf-
fold material should maintain tissue form and function while it
is gradually replaced by newly regenerated tissues. The deg-
radation time for a scaffold material is suggested to be approx-
imately 2 to 4 months based on the healing time that allows for
pulp and dentin regeneration in animal models [2, 4].
Signaling Molecules
Signaling molecules such as growth factors and cytokines
are crucial to the biological process of tissue regeneration.
They initiate a cascade of intracellular and inter-cellular
signaling and modulate cellular behaviors including cell
migration, proliferation, differentiation, angiogenesis, and
neurogenesis [12]. Endogenous signaling molecules such
as growth factors [27, 28, 29•], noncollagenous proteins
[30], and glycosaminoglycans [31, 32] are embedded in
dentin matrix and liberated during demineralization to en-
hance the repair/regenerative processes. Exogenous sig-
naling molecules have been selected and introduced into
the root canal space to fuel and control the cellular activ-
ities of stem/progenitor cells [2–4]. These signaling mol-
ecules can be incorporated into the scaffolds and released
into the surrounding microenvironment during the scaf-
fold degradation by diffusion. Platelet-derived growth fac-
tors [33, 34], transforming growth factors [35, 36], bone
morphogenetic proteins [37, 38], vascular endothelial
growth factors [39], fibroblast growth factors [40],
insulin-like growth factor [41], nerve growth factors
[42], and stromal cell-derived factor 1 [2, 3] have been
used in preclinical and clinical studies.
Curr Oral Health Rep (2016) 3:293–301
Patent Blood Supply
It is unlikely that regeneration can occur without a patent
blood supply. The regeneration of blood vessels
(vasculogenesis/angiogenesis) occurs after the triad of tissue
engineering plays their roles. Evoked bleeding is considered
the influx of stem cells [43] and supply of growth factors,
which will initiate the differentiation of stem cells into endo-
thelial cells as a critical biological event during the early re-
generative processes [39]. In addition, dentin-matrix-derived
growth factors, such as angiogenic factors, are also released in
the canal by ethylene diamine tetraacetic acid (EDTA) treat-
ment [29•]. The regeneration of blood vessels then will allow
the continuous blood supply to the stem/progenitor cells as
well as resident cells within the root canals.
Procedures of Regenerative Endodontics
Root Canal Disinfection
Current disinfection protocols for regenerative endodontic
treatment heavily rely on chemical irrigation without mechan-
ical instrumentation. The American Association of
Endodontists (AAE) has proposed the disinfection regimen
for regenerative endodontic treatment in a recently revised
guideline [44]. According to the AAE guideline, at the first
treatment visit, the lower concentration of sodium hypochlo-
rite (1.5 %) followed by saline or 17 % EDTA is recommend-
ed as chemical irrigants based on the survival of SCAP and
level of dentin sialophosphoprotein expression from an
in vitro study by Martin and colleagues [45]. Use of high
concentrations of sodium hypochlorite and chlorhexidine is
not recommended due to their cytotoxic effects against
SCAP as evinced by Trevino and colleagues [46]. A low con-
centration of triple antibiotics (0.1–1.0 mg/ml) or calcium hy-
droxide should be placed in the root canals as an intracanal
medicament. Ruparel and colleagues showed that antibiotics
with a concentration higher than 1.0 mg/ml were cytotoxic to
SCAP, while calcium hydroxide was not detrimental to the
survival of SCAP regardless of concentrations [47]. All disin-
fection procedures will be completed during the first appoint-
ment and any required inter-appointment period.
Intracanal Bleeding
At the second appointment, 3 % mepivacaine without a vaso-
constrictor is used as an anesthetic solution in order to facili-
tate intracanal bleeding [48]. It has been demonstrated that
bleeding evoked by overinstrumenting the canals beyond the
apical foramen can deliver the mesenchymal stem cells from
periapical tissues to the root canal space in both immature and
mature teeth [43, 49]. Prior to induced bleeding, EDTA is used
295
as a single irrigant not only to wash out the intracanal medi-
cament but also to promote the release of Bfossilized^ biolog-
ical factors within dentin matrix [50, 51]. The biological mol-
ecules such as growth factors are released from EDTA-
conditioned dentin matrix [29•] and control the activities and
fates of stem cells mobilized from evoked bleeding. As an
alternative to induced bleeding, platelet-rich plasma (PRP)
or platelet-rich fibrin (PRF) can be used [52, 53]. These
platelet-rich concentrates contain a variety of growth factors
[54] and may provide the structural support as a scaffold.
Resorbable collagen matrix can be placed over the blood clot
to facilitate the placement of restorative materials [48].
Coronal Seal
Use of two distinct materials is advised as final coronal seal
according to the AAE guideline [44]. A material conducive to
hard tissue regeneration is placed in the inner layer where stem
cells can attach and differentiate into mineral-forming cells
while a material that provides structural integrity and longev-
ity is used in the outer layer. Calcium silicate-based cements
such as mineral trioxide aggregate are suitable for the inner
layer due to superior biocompatibility [55] as well as sealing
ability [55]. They can be placed over the blood clot or resorb-
able collagen matrices around the cementoenamel junction.
Recently, mineral trioxide aggregate is reported to cause sig-
nificant tooth discoloration [56, 57•], and therefore, it should
not be used in esthetic areas. Biodentine® (Septodont,
Lancaster, PA, USA) can be used as an alternative calcium
silicate-based cement. A 3–4-mm thickness of glass ionomer
or composite resin is commonly used as a permanent restora-
tion to prevent coronal leakage.
Is Regenerative Endodontics a Regenerative
or Reparative Process?
Clinically, many studies of immature teeth with necrotic pulps
in animals and humans after regenerative endodontic therapy
have showed, in addition to elimination of symptom/sign and
resolution of apical periodontitis, radiographic evidence of
thickening of the canal walls and/or continued root develop-
ment [58–61, 62•]. Therefore, it was assumed that regenera-
tive endodontic therapy was capable of regenerating the
dentin-pulp complex. The speculation was based on possible
survival of residual pulp tissue in the apical canal [7, 8] or the
apical papilla in the periapical area [15] in immature teeth with
necrotic pulp/apical periodontitis, as mesenchymal stem cells
from the dental pulp [63] and the apical papilla [15] were
shown to be capable of differentiating into odontoblast-like
cells and produce dentin-like mineralized tissue after receiving
appropriate signaling molecules, such as growth/
differentiation factors. However, the nature of tissue formed
296
in the canals of immature teeth with necrotic pulps after re-
generative endodontic therapy can only be determined by his-
tological examination. Histologically, the tissues formed in the
canals of immature teeth with necrotic pulps after regenerative
therapy in animals and humans have revealed that the newly
formed tissues are cementum-, bone-, and periodontal
ligament-like tissue and not genuine dentin and pulp tissue
[59, 64–69]. Therefore, regenerative endodontics is consid-
ered a reparative and not a regenerative process histologically
[70, 71]. Although repair is not an ideal histological wound
healing, it is not a failure of clinical endodontic treatment. In
patient-centered treatment outcome, elimination of infection
or disease and maintenance of the tissue/organ function are the
primary goal. The tissues formed in the canals of immature
teeth after regenerative endodontic therapy are the host’s own
vital tissue with an immunoinflammatory defense mechanism
to protect against foreign invaders, such as microbes.
Current Status in Clinical Regenerative Endodontics
Since an update on clinical regenerative endodontics of im-
mature permanent teeth with necrotic pulp/apical periodontitis
in 2013 [62•], no new advances in this area have been report-
ed. However, recently, regenerative endodontics has been
employed to treat mature teeth with necrotic pulps, teeth with
persistent apical periodontitis after conventional root canal
treatment, and traumatized teeth associated with horizontal
root fracture, root resorptions, and avulsion.
Immature Permanent Teeth with Necrotic Pulps
Traditionally, immature permanent teeth with necrotic pulps
are treated with calcium hydroxide apexification to induce
apical hard tissue barrier formation or with mineral trioxide
aggregate apical plug to create a barrier to prevent extrusion of
root canal filling material into the periapical tissues [72]. The
outcome of calcium hydroxide or MTA apexification treat-
ment is predictable [72]. However, thickening of the canal
walls and/or continued root development cannot occur after
apexification, thus rendering the immature teeth with already
thin and fragile canal walls more prone to cervical root frac-
ture [73]. It has also been shown that a long-term calcium
hydroxide dressing in the canal of immature permanent teeth
could weaken the thin and fragile root structure, thus
increasing likelihood of root fractures [74]. Therefore,
revascularization/regenerative endodontic therapy has be-
come a preferable treatment option over apexification for im-
mature permanent teeth with necrotic pulps [62•]. Thickening
of the canal walls and/or continued root development, al-
though not always predictable after regenerative endodontic
procedures, is considered to be the desirable outcome because
it may strengthen the root and increase the root/crown ratio
Curr Oral Health Rep (2016) 3:293–301
[62•]. Although randomized, prospective clinical trials of re-
generative endodontic therapy of immature permanent teeth
with necrotic pulps are still lacking, the best available evi-
dence seems to support that regenerative endodontic therapy
is a feasible treatment option for immature permanent teeth
with necrotic pulps [75••].
Mature Permanent Teeth with Necrotic Pulps
Mature permanent teeth with necrotic pulps are traditionally
treated with pulpectomy and root canal filling. The outcome
of primary root canal treatment varies considerably depending
on the presence or absence of apical periodontitis [76] and the
assessment criteria used [76, 77]. Although the technology
and materials used in nonsurgical root canal therapy have been
greatly improved, the outcome of nonsurgical root canal treat-
ment of mature permanent teeth with apical periodontitis has
not improved significantly for several decades [76].
Recently, regenerative endodontic therapy has been
employed to successfully treat mature permanent teeth with
necrotic pulps and apical periodontitis [78–80], based on the
rationale of elimination of clinical symptom/sign and resolu-
tion of apical periodontitis. Unlike immature teeth having
large canal space, irrigation and intracanal medication cannot
be effectively delivered into and disinfect the small canals of
mature teeth. Therefore, completely chemomechanical de-
bridement is required to remove necrotic tissue and eliminate
bacterial biofilm in the canals. The major difference between
regenerative endodontic therapy and nonsurgical root canal
treatment is that the disinfected canal in the former is filled
with the host’s own vital tissue and the canal in the latter filled
with nonvital foreign materials. Regenerative endodontic ther-
apy has the potential to be used to treat mature teeth with
necrotic pulps.
Teeth with Persistent Apical Periodontitis After Root
Canal Therapy
Traditionally, teeth with persistent apical periodontitis after
root canal therapy are managed with nonsurgical root canal
therapy. Endodontic surgery is usually indicated if nonsurgical
treatment is not feasible. In principle, treatment of secondary
and primary root canal is similar, except that more complete
root canal infection control protocol is required in secondary
root canal therapy. Recently, regenerative endodontic therapy
has also been used to manage teeth with persistent apical peri-
odontitis after root canal therapy [81–83]. The treatment was
able to eliminate clinical symptom and resolve apical peri-
odontitis. Therefore, regenerative endodontic therapy offers
another potential for retreatment of teeth with persistent apical
periodontitis after primary root canal treatment.
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Traumatized Teeth Associated with Inflammatory Root
Resorptions, Horizontal Root Fracture, and Avulsion
Traumatized teeth with inflammatory root resorptions, hori-
zontal root fracture, and complete avulsion are traditionally
managed with control of root canal infection using chemo-
mechanical debridement and root canal filling [84].
Recently, regenerative endodontic therapy has been employed
to manage traumatized teeth with horizontal root fracture, in-
flammatory root resorptions, and complete avulsion [85, 86].
Therefore, regenerative endodontic therapy has the potential
to be used to manage complex traumatic injuries and should
be explored further.
Outcomes of Clinical Regenerative Endodontics
Regression of Clinical Symptom/Sign and Resolution
of Apical Periodontitis
The regression of clinical symptoms/signs and radiographic
evidence showing resolution of apical periodontitis is consid-
ered the optimal outcome for all endodontic treatments. The
AAE [44] clinical considerations for regenerative endodontic
procedures also state this as a primary goal of treatment [44].
Resolution of periapical lesions appears to be a more predict-
able outcome after regenerative endodontic therapy of imma-
ture teeth with necrotic pulps [87–89].
Thickening of the Canal Walls and/or Continued Root
Development
Regenerative endodontic therapy has been advocated as a
Bparadigm shift^ in the treatment of immature teeth with in-
fected necrotic pulps, as there is potential for further thicken-
ing of the canal walls and/or root maturation [90]. Yet, in-
creased root canal wall thickness and/or increased root length
is only a secondary goal following regenerative endodontic
therapy [44]. Many reports show that further root maturation
and apical closure are often achieved. However, it is not a
consistent finding with variable results reported [89, 91–93].
In a quantitative analysis of changes in root length and width,
increases in root wall thickness were more reliably achieved
with regenerative endodontic therapy using triple antibiotic
paste as a medicament, whereas increases in root length was
greater when calcium hydroxide was the medicament placed
[87]. A recent systematic review reported that 97 of 101 teeth
(96 %) treated with regenerative endodontic therapy showed
some degree of further root maturation. Apical closure was
detected in 55.4 % of teeth with increased root length
(76.2 %) and increased root width (79.2 %) reported more
frequently. These outcomes were independent of clinical var-
iables such as operator and material selection or differences in
297
protocols [94]. The finding of increased root length of 79.2 %
differs from cohort studies that reported 5 % [95], 15 % [88],
and less than 20 % [89] changes in root length. It has also been
suggested that severe trauma has the potential to produce dam-
age to the Hertwig’s epithelial root sheath and/or the apical
papilla and that teeth subjected to trauma may be less likely to
achieve clinically meaningful continued root development
than treated immature teeth with pulpal necrosis caused by
caries or dens evaginatus [89].
Return of Tooth Vitality
Return of tooth vitality is considered a tertiary goal for regen-
erative endodontic therapy [44]. Many studies report a return
to vitality after regenerative endodontic therapy [62•]. A pos-
itive response to vitality testing may indicate a more organized
vital pulp tissue [44]. However, response of immature teeth
after regenerative endodontic therapy does not necessarily in-
dicate regeneration of pulp tissue in the canals. It simply im-
plies whatever tissue in the canal is innervated by sensory
nerve fibers.
Discoloration of Teeth
Discoloration of teeth following regenerative endodontic ther-
apy has been recently reviewed with minocycline included in
the triple antibiotic paste, which is considered the main cause
for discoloration [57•]. However, discoloration has also been
reported when calcium hydroxide was used as the intracanal
medicament [93]. Mineral trioxide aggregate has also been
shown to discolor teeth [96] and is the most commonly used
material placed on the induced blood clot as an intracanal
barrier in regenerative endodontic procedures [97]. The
AAE guidelines advise that patient's should be advised of
the risk of discoloration of the crown following regenerative
endodontic therapy [44].
Level of Evidence
A review of published reports on teeth treated with regenera-
tive endodontic therapy identified 51 clinical studies with 255
treated teeth [75••]. There are only two high-level cohort stud-
ies (level of evidence (LOE) 2), eight case series studies (LOE
4), and 41 case reports (LOE 5) [75••]. There must be a pub-
lication bias in the reports of regenerative outcomes, as it is
likely that successful cases are being more often submitted for
publication. Randomized, prospective large scale of clinical
trials is needed to determine outcomes for teeth treated with
regenerative endodontic therapy.
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Table 1 Some cell-based and cell-free approaches to pulp tissue regeneration in vivo

Author/year Scaffold Signaling Stem cells Finding

molecules

Cell-based approach since 2012

Ishizaka et al. 2012 [3] Collagen with SDF-1 No Dog pulp, BM, adipose Pulp-like tissue regeneration
CD31.SP cells
Iohara et al. 2013 [4] Collagen with G-CSF No Dog mobilized DPSCs Pulp-like and dentin-like tissue
regeneration
Murakami et al. 2013 [101] Collagen No Human mobilized DPSCs Pulp-like tissue regeneration
Rosa et al. 2013 [102] Peptide HY No SHEDs Odontoblast-like cells
Nakashima and Iohara 2014 [103•] N No Human mobilized DPSCs Pulp-like tissue regeneration
Cell-free or cell-homing approach since 2010
Kim et al. 2010 [98•] Collagen gel Y1 No Dental-pulp-like tissue regeneration
Zhang et al. 2015 [99] Collagen gel Y2 No Dental-pulp-like tissue regeneration
Yang et al. 2015 [100] Silk fibroin Y3 No Pulp-like tissue

DPSCs dental pulp stem cells; G-CSF granulocyte colony-stimulating factor; HY hydrogel; SDF-1 stromal cell-derived factor-1; SHED stem cells from
human exfoliated deciduous teeth; Y1 vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, nerve growth
factor, bone morphogenetic protein-7; Y2 stromal cell-derived factor-1; Y3 stromal-derived factor-1α

Future Prospects ex vivo expansion of stem cells, good manufacturing

Up to date, most studies of pulp tissue regeneration have
been focused on in vivo de novo regeneration and a few
studies on in situ regeneration. Currently, there are two
approaches to pulp tissue regeneration in regenerative
endodontics, namely, cell-free and cell-based approaches
(Table 1). Both approaches are based on the concept of
tissue engineering applying stem cells, biomimetic scaf-
fold, and bioactive growth/differentiation factors. The
cell-free or cell-homing approach involves transplantation
of biomimetic scaffold incorporated with bioactive growth
factors or chemoattractants into the canal space to recruit
endogenous stem cells [98•, 99, 100]. Clinically, revascu-
larization or regenerative endodontic procedures can be
considered a cell-free approach. The cell-based approach
requires isolation and ex vivo expansion of stem cells
seeded in the scaffold and then transplanted into the canal
space [3, 4, 25, 26, 101, 102, 103•]. Technically, cell-free
approach is simpler than cell-based approach because the
former does not have to be concerned about stem cell
source and isolation. However, in cell-free approach, the
endogenous stem cells are not pulp tissue specific and can
be from apical papilla, periodontal ligament, or bone mar-
row. The cell-based approach employs pulp tissue-specific
stem cells, such as dental pulp stem cells [63], stem cells
from exfoliated deciduous teeth [104], and stem cells
from apical papilla [15]. These stem cells have been
shown to be capable of differentiating into odontoblast-
like cells and produce dentin-like mineralized tissue [15,
63, 104]. Nevertheless, several problems are associated
with cell-based approach and have to be resolved, such
as limited availability of stem cell source, isolation and
practice facilities, contamination, stem cell bank, cost,
regulatory issues, and clinician’s ability to perform stem
cell transplantation [105, 106]. Basically, both cell-free
and cell-based approaches of pulp tissue regeneration are
still in the preclinical stage of experiments [105].
However, the future prospect of pulp tissue regeneration
appears to be an attainable goal, based on the concept of
stem cell-based pulp tissue engineering [107].
Conclusions
Regenerative endodontics presents a new era in biological and
clinical endodontics. Although this biologically based treat-
ment is still in the stage of preclinical trial, regenerative end-
odontic therapy can become a clinical reality in the near future
because of rapid advance in pulp tissue engineering/pulp tis-
sue regeneration research. Clinicians must be familiar with the
concept of regenerative endodontics in order to apply this
treatment in their routine clinical practice to achieve optimal
treatment outcome for their patients. As our knowledge in
pulp biology advances, our concept of clinical endodontic
therapy may also be evolved accordingly to improve the treat-
ment outcome.
Compliance with Ethical Standards
Conflict of Interest Sahng G. Kim, Bill Kahler, and Louis M. Lin
declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent The article does
not contain any studies with human and animal subjects performed by any
of the authors.
Curr Oral Health Rep (2016) 3:293–301
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