SPECIALTY UPDATE
ENDODONTICS

Regenerative endodontics
A way forward
Anibal Diogenes, DDS, MS, PhD; Nikita B. Ruparel, DDS, MS,
PhD; Yoav Shiloah, DDS, MBA; Kenneth M. Hargreaves,
DDS, PhD
I
mmature teeth are at risk of developing pulpal ne-
crosis due to trauma, caries, and anatomic variations
such as dens evaginatus and dens invaginatus.1-4
Dental trauma occurs with an incidence that varies
from 2.6% to 35% in patients undergoing cranioskeletal
development.5-7 Up to one-half of these traumatized
teeth may undergo pulpal necrosis, but only 8.5% will
exhibit signs and symptoms of disease.8 Dental anoma-
lies also represent a common etiology leading to pulpal
necrosis in immature permanent teeth.4 Dens evaginatus
and dens invaginatus are the most common anomalies
associated with this clinical manifestation.4 Full radicular
maturation occurs up to 3 years after the eruption of a
tooth in the oral cavity,9 and the loss of pulp vitality
during this period arrests further root development.
These teeth traditionally have been treated with apexifi-
cation procedures by using either long-term calcium
hydroxide treatment10,11 or immediate placement of a
mineral trioxide aggregate (MTA) apical plug.12
Although these treatments often result in the resolution
of signs and symptoms of disease, they provide little
to no benefit in restoring normal pulpal defenses and
nociception and, more importantly, continued root
development.13 Thus, immature teeth remain with thin
fragile dentinal walls, increasing susceptibility to frac-
tures and lower survival rates.14,15
Tooth loss in patients still undergoing cranioskeletal
development has devastating consequences that include
altered maxillary and mandibular bone development;
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ABSTRACT
Background and Overview. Immature teeth are sus-
ceptible to infections due to trauma, anatomic anomalies,
and caries. Traditional endodontic therapies for immature
teeth, such as apexification procedures, promote resolution
of the disease and prevent future infections. However, these
procedures fail to promote continued root development,
leaving teeth susceptible to fractures. Regenerative end-
odontic procedures (REPs) have evolved in the past decade,
being incorporated into endodontic practice and becoming
a viable treatment alternative for immature teeth. The au-
thors have summarized the status of regenerative end-
odontics on the basis of the available published studies and
provide insight into the different levels of clinical outcomes
expected from these procedures.
Conclusions. Substantial advances in regenerative end-
odontics are allowing a better understanding of a multitude
of factors that govern stem cell–mediated regeneration and
repair of the damaged pulp-dentin complex. REPs promote
healing of apical periodontitis, continued radiographic root
development, and, in certain cases, vitality responses.
Despite the clinical success of these procedures, they appear
to promote a guided endodontic repair process rather than
a true regeneration of physiological-like tissue.
Practical Implications. Immature teeth with pulpal
necrosis with otherwise poor prognosis can be treated with
REPs. These procedures do not preclude the possibility of
apexification procedures if attempts are unsuccessful.
Therefore, REPs may be considered first treatment options
for immature teeth with pulpal necrosis.
Key Words. Guided tissue regeneration; revasculariza-
tion; endodontic therapy; stem cells; outcome assessment;
regenerative endodontics.
JADA 2016:147(5):372-380
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 SPECIALTY UPDATE
interference with pronunciation, breathing, and masti-
cation; and a severe detrimental psychosocial effect.16,17
Because implants are contraindicated in growing young
patients because of continued craniofacial development,
tooth replacement is not possible until the age of
maturity (usually older than 18 years). As an alternative
technique, regenerative endodontic procedures (REPs)
are intended to promote tooth survival and the function
of previously thought hopeless teeth. In this review, we
will focus on discussing the historical background and
the present and future directions of these clinical
procedures.
HISTORY
The emergence of regenerative endodontics was catalyzed
in the early 2000s with the publication of 2 remarkable
case reports.18,19 However, this field has its roots in the
seminal work by Dr. Ostby in the early 1960s that aimed
to evaluate the role of the apical blood clot in the healing
of apical periodontitis and pulp repair.20,21 Regenerative
endodontics also relied on contributions from important
studies in dental trauma, which provided evidence that
the dental pulp in immature teeth often remains vital
despite substantial traumatic injuries such as intrusions
and avulsions.22-24 This remarkable regenerative potential
is highlighted in cases of replantation of avulsed imma-
ture teeth with evidence of reestablishment of vitality
responses and lack of signs and symptoms of dis-
ease.23,25,26 In these cases, clinical success relies heavily on
the reestablishment of a blood supply to the ischemic but
uninfected dental pulp tissue, followed by reinnervation
from sensory axons likely recruited from the apical re-
gion. This healing process of a previously necrotic dental
pulp in traumatic injuries is crucial for reattaining normal
pulpal function after trauma. The term revascularization
has emerged from these observations in dental trauma-
tology despite the different application and goals.4 Pulpal
revitalization is another commonly used term in the
scientific literature. However, for the sake of this review,
we simply will address these procedures collectively as
REPs. Results from numerous published reports
demonstrate that these procedures often lead to resolu-
tion of apical periodontitis and signs and symptoms of
inflammation, radiographic evidence of continued root
development and apical narrowing, and restoration of
vitality responses.4,27,28 These published cases establish
that REPs address the unmet need of promoting normal
physiological development and responses in immature
teeth with pulpal necrosis.
In most REPs, clinicians rely on creating bleeding
from the apical region that passively fills the canal space
and forms a blood clot. However, it was not until 2011
that investigators in a clinical study demonstrated that
the influx of apical blood into disinfected root canals
was accompanied by a clinically significant transfer of
mesenchymal stem cells into the root canal system.29
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This was an important demonstration in the field of
regenerative endodontics because it established that these
procedures were, in fact, stem cell–based procedures. The
realization that autogenous stem cells can be delivered
clinically into root canals without the need for ex vivo
stem cell expansion propelled researchers and clinicians
to consider principles of tissue engineering to improve
treatment protocols and to develop the next generation
of procedures.
TRANSLATIONAL STUDIES
The balance between adequate disinfection and stem cell
survival, proliferation, and differentiation represents an
important initial barrier to overcome. The resolution of
infection and the disease process remains the primary
goal of any endodontic procedure. However, it has
become obvious that the philosophy of disinfecting the
root canal by using methods typically advocated in
traditional root canal therapy had to be modified to
attain a biocompatible disinfection strategy. To maintain
the physical integrity of the already thin dentinal walls of
immature teeth, investigators have advocated chemical
debridement as the primary means of disinfection. To
this end, investigators in many translational studies have
focused efforts on establishing the biological basis for
clinical protocols that could achieve both disinfection
and optimum regenerative potential.4,27 For example,
sodium hypochlorite remains the most used disinfectant
in endodontics.30 However, its use at full concentration
of 6% denatures crucial growth factors in dentin31 and
results in residual detrimental effects greatly affecting
stem cell attachment, survival, and differentiation po-
tential.32-35 These deleterious effects largely can be avoi-
ded with the use of a 1.5% concentration of sodium
hypochlorite followed by 17% ethylenediaminetetraacetic
acid.35,36 Furthermore, results from elegant studies have
demonstrated that ethylenediaminetetraacetic acid pro-
motes the release of growth factors embedded in dentin,
including vascular endothelial growth factor and trans-
forming growth factor beta-1 among others that are
known to participate actively in regenerative processes
such as angiogenesis and stem cell proliferation, migra-
tion, and differentiation, respectively.37-39
Along these lines, it was obvious that the effects of
intracanal medicaments be tested on the survival and
maintenance of stem cells. A triple antibiotic formulation
consisting of ciprofloxacin, metronidazole, and minocy-
cline first was tested in vitro against bacteria isolated
from carious lesions and from endodontic infections
in primary teeth.40 The investigators found that no
bacteria could be recovered after treatment with 100
ABBREVIATION KEY. MTA: Mineral trioxide aggregate.
NSRCT: Nonsurgical root canal therapy. REP: Regenerative
endodontic procedure.
JADA 147(5) http://jada.ada.org May 2016 373
 SPECIALTY UPDATE
micrograms per milliliter of each antibiotic (300 mg/mL
of mixture).40 Next, investigators carried out studies to
test the efficacy of triple antibiotic paste in eradicating
bacteria from infected dentin. They found that there
were no recovered cultivable bacteria at 48 hours, and
they found evidence of significant drug penetration into
dentin.40 In REPs, the use of the triple antibiotic paste
and its modified versions, such as exclusion of minocy-
cline, known as double antibiotic paste, or the addition
of cefaclor, were introduced by initial published case
reports.19 The drugs were mixed with water, saline,
or propylene glycol until a thick creamy mixture was
formed. In these case reports, there was no attempt to
deliver a specific concentration of the drugs deliberately.
Instead, the investigators mixed the drugs until they
achieved a certain physical consistency (approximately
1 gram per milliliter) that clinicians deemed suitable. At
this concentration, however, the triple antibiotic paste
appeared to have long-lasting deleterious effects on stem
cell survival through both direct and indirect mecha-
nisms.41,42 This undesirable effect can be avoided greatly
by the use calcium hydroxide as an intracanal medica-
ment41,42 or the use of these pastes in lower concentra-
tions (less than 1 milligram/mL); these lower
concentrations retain the desirable antibacterial or anti-
biofilm effect.43-46 Therefore, there have been substantial
advances in understanding how to adapt disinfection
protocols to the new reality of stem cell–based therapies.
In addition to studies on biocompatible disinfection,
many other frontiers in regenerative endodontic research
are being investigated. These involve tissue engineering
strategies that include the evaluation of suitable scaffolds,
growth factors, and harvested stem cells to be used in
pulp-dentin regeneration.47 Many of the advances from
translational research have been evaluated in a clinical
setting, including the use of platelet-rich plasma,48,49
platelet fibrin,50 and a gelatin hydrogel51 as scaffolds in
patients. In addition, a groundbreaking clinical trial is
being conducted in Japan.52 This trial involves harvesting
stem cells from a donor site, followed by ex vivo
expansion, sorting, and maintenance of these cells in a
good manufacturing practice facility, followed by auto-
genic transplantation into a recipient tooth to promote
the regeneration of the once lost functional pulp-dentin
complex. These elegant studies highlight the status
and sophistication of REPs.
CLINICAL OUTCOMES OF REPs
Resolution of infection and the signs and symptoms of
inflammation leading to apical periodontitis and resto-
ration of lost function remains the primary goal of any
endodontic therapy. Traditional endodontic therapies
(nonregenerative procedures) achieve this goal by pro-
moting disinfection followed by a fluid-tight or bacteria-
tight seal of the root canal system and delivery of a
high-quality coronal restoration. The clinical outcome
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of endodontic therapies traditionally has been evaluated
on the basis of lack of signs and symptoms of disease,
such as pain, swelling, or sinus tracts, and radiographic
criteria of healing.10,11,53 REPs, on the other hand, rely on
comparably efficient chemical disinfection followed by
the stem cell–mediated growth of a reparative tissue that
promotes continued root development and reestablish-
ment of pulpal functions such as nociception and im-
mune competency. This paradigm shift in treatment
approach also requires a shift in assessment of clinical
outcomes.54,55 Last, the success of these procedures must
be evaluated by 3 stakeholders: patients and their legal
guardians, clinicians, and researchers.
Patient-based outcomes. The needs and desires of
patients might not always align with the preset criteria
of success laid out by clinicians and researchers. There
is an ever-increasing need to focus on outcomes that
are meaningful to patients because they are the primary
stakeholders in their own health and must participate
in treatment decisions.56 However, even in the context of
long-established therapies such as conventional nonsur-
gical root canal therapy (NSRCT), there is often a
disconnect with patient-centered outcomes. For example,
from a patient perspective, the resolution of pain may be
the most important criterion for successful NSRCT.
However, for most clinicians, success also means healing
of a periapical lesion, if present.57 Other patient-centered
outcomes may include tooth survival in the mouth and
acceptable esthetics. These patient-centered outcomes
are also relevant for REPs (Figure 1).
Investigators used standardized treatment protocols
in a study to compare REPs directly with apexification
procedures by using the long-term application of calcium
hydroxide or by using MTA as an apical plug.15 REPs and
MTA plug apexification procedures were equally effec-
tive in resolving signs and symptoms of disease (that is,
pain, swelling, or sinus tract) in 100% and 95% of all
patients, respectively, whereas apexification procedures
with the use of calcium hydroxide were significantly
less effective (77%). Investigators in another retrospective
study did not include standardization of treatment
protocols and found REPs to promote healing in 79%
of patients treated, whereas apexification procedures
promoted healing in 100% of the patients; however, this
difference was not significant.58 In a prospective study,
investigators found that both MTA apexification and
REPs promoted healing in 100% of patients.51 Further
evidence of successful outcomes can be found in case
series and retrospective patient cohort studies. Despite
significant variations in etiology, inclusion and exclusion
criteria, and clinical protocols, results from these
studies51,58 demonstrate that both procedures can resolve
the signs and symptoms of disease in approximately 90%
of patients successfully, without marked difference in
resolution of symptoms between REPs and apexification
procedures.
 SPECIALTY UPDATE

Survival of the tooth is

another important
patient-centered
outcome. An ideal treat- Scientist-Based
ment, from the patient’s Outcomes Histologic
perspective, is one that evidence
prolongs the functional of complete
life of an asymptomatic regeneration
tooth. The survival of
a permanent tooth is Clinician-Based
Outcomes • Radiographic healing
particularly important in • Radiographic root development
young patients undergo- • Positive vitality responses
ing continued cranioske-
letal development • Resolution of disease
because implants are Patient-Based (absence of swelling, drainage, and pain)
contraindicated at this Outcomes • Tooth survival and function
59
stage. Although results • Tooth esthetics
from various studies
demonstrate the func-
tional survival of mature Figure 1. Trilevel outcome assessment pyramid. Regenerative endodontic procedures must be assessed and
teeth treated with con- evaluated in a systematic manner, acknowledging that there are different levels of possible outcomes that carry
ventional NSRCT,60,61 far different meanings for patients, clinicians, and scientists. The patient-centered outcomes represent the base of
this pyramid, symbolizing the fundamental importance of achieving healing, reestablishment of function, and
less is known about the patient satisfaction.
effect of either apex-
ification or REPs on tooth
survival. REPs promoted 100% survival in a study period Clinician-based outcomes. As mentioned, clinician-
of 18 months, which was comparable with the 95% survival based outcomes involve radiographic signs of healing;
promoted by MTA apexifications, both being superior however, unique to REPs, clinicians also evaluate for
to the 77% survival achieved in calcium hydroxide– continued root development by means of radiographic
mediated apexification procedures.15 Another retrospec- examination and responses to pulp sensitivity. Initially,
tive study in which the investigators directly compared investigators in case reports and case series relied
the survival of REPs and apexification (MTA apical plug) on reporting the nonquantitative assessment of root
procedures failed to demonstrate differences between the development, often using a dichotomous dependent
treatment alternatives.58 Nonetheless, investigators have measure (that is, yes or no),74 in addition to qualitative
shown that REPs arrest the disease process and promote descriptions of radiographic findings.75 In 2009, study
retention of teeth with otherwise poor prognosis.4,27 investigators published a new methodology to quan-
Factors affecting the long-term survival of these teeth titate changes in root width and length13 and further
require further investigation by means of randomized refined and revised it in a later study.76 It allows
clinical trials to compare REPs with MTA apexification for the digital alignment of nonstandardized radio-
as the criterion standard during long follow-ups. graphs obtained at different recall visit times in pa-
There have been esthetic concerns with REPs that result tients undergoing cranioskeletal growth. It allows the
in coronal staining in certain cases.62-64 This coronal unbiased measurement of changes in root development
staining has been identified as being the result of triple detected by means of conventional 2-dimensional
antibiotic paste in which minocycline stains the dentin, periapical radiographs. With use of this methodology,
prior intracoronal bleeding, or the coronal placement of teeth treated with REPs showed a significantly greater
MTA.63,65-69 This expected staining can be minimized by percentage of increase in root length and width.
occluding the dentinal tubules with a dental adhesive if This finding later was confirmed in another retro-
either triple antibiotic paste or MTA is used.62 Alterna- spective study in which the investigators reported
tively, other bioceramic materials, such as Biodentine gains in root length (14.9%) compared with teeth
(Septodont), Bioaggregate (Pearson Dental), and Endo- treated by means of either MTA apexification (6.1%)
Sequence Bioceramic Root Repair Material putty (Brass- or calcium hydroxide apexification (0.4%).15 They
eler), are biocompatible and are osteoinductive when also reported that the REPs produced a significantly
exposed to mesenchymal stem cells70-73 while showing greater percentage of increases in root width (28.2%)
minimal to no color change.67 Thus, tooth discoloration as compared with that in teeth treated by means of either
an adverse event of REPs largely can be avoided if non- MTA apexification (0.0%) or calcium hydroxide
staining medications and restorative materials are used. apexification (1.5%).

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 SPECIALTY UPDATE

Figure 2. A. A 12-year-old boy sought care for intraoral buccal swelling and sinus tract associated with tooth no. 29. B. Clinical examination revealed
a talon cusp (dens evaginatus) on the occlusal aspect of the tooth. Clinical findings led to the diagnosis of pulpal necrosis with chronic apical abscess.
C. A preoperative radiograph revealed a large apical radiolucency traced with a gutta-percha point through a sulcular sinus tract, an immature root
with a large pulp canal space, and thin dentinal walls. The tooth was treated by means of a regenerative endodontic procedure by using a mixture of
ciprofloxacin, metronidazole, and minocycline (triple antibiotic paste) as an intracanal mixture for 40 days. Incision and drainage also was performed
at this visit. At the second visit, after removal of the intracanal medicament and evoked bleeding, a 3-millimeter piece of absorbable wound dressing
(CollaPlug, Integra LifeSciences) was placed at the level of the cementoenamel junction and restored with a 3-mm layer of mineral trioxide aggregate
and light-cured glass ionomer (Fuji II LC, GC America). At the 4-year recall visit, the patient was asymptomatic and demonstrated positive response to
electric pulp testing for tooth no. 29. Radiographic examination revealed complete apical closure, as well as clinically significant gain in root length
and width with narrowing of the pulp canal space as seen in the periapical radiograph (D) and small-volume cone-beam computed tomography in the
coronal (E) and sagittal (F) views. Photographs and radiographs courtesy of Dr. Yoav Shiloah, University of Texas Health Science Center at San Antonio,
San Antonio, TX.

Further evidence of continued root development is
available in a prospective randomized clinical trial in
which the investigators compared 2 different protocols of
REPs with MTA apexification procedures.51 In this study,
REPs promoted the gain in root length (12% increase)
and width (13% increase), whereas no changes were
detected in the MTA apexification group.51 Investigators
in other studies with similar methodologies also reported
changes in radiographic root structure but failed to
detect statistical significance, possibly because of limited
sample size or large variability of responses.58,77
Various degrees of radiographic root development
have been observed in most published studies. The factors
that modulate this varied response are largely unknown
because correlation with factors such as tooth type, eti-
ology, sex, or age has not been established.15,58 Thus,
although REPs predictably promote healing of apical
periodontitis in more than 90% of the cases,4,15,51,58,74
radiographic root development is far less predictable.
Figures 2 and 3 provide examples of varied root devel-
opment. Figure 2 presents a case that shows excellent gain
in root length and root width along with complete apical
closure, whereas Figure 3 presents a case that shows
only closure of the apex with no gain in root length or
width. Although the lack of radiographic root develop-
ment in absence of disease does not constitute a treatment
failure, future studies with appropriate sample sizes are
needed to find prognostic factors for root development.
Positive responses to pulpal sensitivity tests are
interpreted as evidence favoring the presence of a vital
pulp.78 Clinicians routinely use these tests as adjuvants in
the diagnosis of pulp status. Investigators have reported
positive sensitivity responses to either cold or electric
pulp tests in approximately 60% of all published cases.4
Nociception is an important surveillance mechanism
that protects tissues against actual or potential damage.
The reestablishment of nociception in these teeth must
be seen favorably because it suggests the presence of a
vascularized tissue with normal physiological responses.
Furthermore, primary afferent neurons in the dental
pulp are equipped to sense microbial antigens, partici-
pating in the inflammatory process evoked by invading
microorganisms.79,80 They modulate the immune reac-
tion by the release of neuropeptides with vasoactive
properties that increase immune cell recruitment and
vascularity, localizing areas of insult to microabcesses

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 SPECIALTY UPDATE

Figure 3. A 10-year-old boy had trauma of tooth no. 8 with an uncomplicated crown fracture and moderate intrusive luxation. The tooth had pulpal
necrosis and symptomatic apical periodontitis approximately 6 months after injury. A. A preoperative periapical radiograph revealed a moderately
immature root with an apical radiolucency and inflammatory root resorption. The tooth was treated with a regenerative endodontic procedure by using
a mixture of ciprofloxacin and metronidazole (double antibiotic) as an intracanal medicament for 1 month. At the second visit, after medicament
removal and evoked bleeding, the access was restored with a 3-millimeter layer of mineral trioxide aggregate placed at the cementoenamel junction
over the blood clot, followed by a base layer of glass ionomer and a composite restoration. At the 3-year recall visit, the patient was asymptomatic, and
the tooth responded to electric pulp testing with evident resolution of the apical radiolucency, arrestment of the resorptive process, and thickening of
the apical one-third with apical closure detected on a periapical radiograph (B). At the 6-year recall visit, the tooth remained asymptomatic with positive
responses to electric pulp testing and evidence of apical closure seen on the periapical radiograph (C) and small-volume cone-beam computed to-
mography in the coronal (D), axial (E), and sagittal (F) views. Radiographs and computed tomographic scans courtesy of Dr. Tyler Lovelace, University of
Texas Health Science Center at San Antonio, San Antonio, TX.

within the dental pulp.81 Also, trigeminal neurons in-
crease odontoblastic differentiation and dentinogenesis.82
Lastly, trigeminal neurons harbor an important sub-
population of mesenchymal stem cells along their axonal
projections that participate in tooth formation. The role
of the perineuronal mesenchymal stem cells in post-
development repair or regeneration remains largely
unknown. Mesenchymal stem cells delivered into root
canals in REPs may be capable of releasing potent soluble
factors that attract nearby neurons to reinnervate the
newly formed tissue, possibly participating in the
reparative process.83
Clinicians rely on the preestablished criteria of
radiographic continued root development and vitality

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 SPECIALTY UPDATE
responses to evaluate clinical outcomes further. Although
these dependent measures add valuable information that
can be used to determine whether further interventions
are needed, their meaning to patients and their guardians
is not entirely clear because their expectation is that the
tooth is pain free and functional. The clinician-centered
criteria, which often are used to evaluate REPs, are not
directly applicable to apexification procedures because
root development and vitality responses are not expected.
Scientist-based outcomes. Outcomes that are not
related directly to the clinical manifestation of the treated
tooth but that address a specific question that requires
scientific methodology in its evaluation should be cate-
gorized as scientist-based outcomes. These are equally
important outcomes because they tend to, through sci-
ence, move the field forward leading to substantial future
advances in care. Histologic evaluation of teeth that were
treated previously with REPs but later extracted because
of recurring trauma and fractures suggests that the newly
formed tissue does not resemble the lost dental pulp.84-86
This is the best example of a scientist-based outcome
because it has strong scientific merit, but it does not
necessarily interfere with consideration of the rate of
healing and continued root development seen in cases
treated with REPs.
There is considerable debate about the use of the term
regeneration because existing scientific evidence from
histologic studies suggests that the procedures allow for
repair instead.87 This is both a semantic and a biological
debate; however, it can be argued that true regeneration
as defined by the complete recapitulation of the lost
tissue with all its constituents, morphology, function, and
molecular markers typically is observed only in primitive
invertebrates such as hydras and in some amphibians
such as salamanders.88 To date, even in sophisticated
animal models, the tissues formed closely resemble the
native dental pulp, but true odontoblasts are missing;
instead, mineralizing cells called odontoblast-like cells are
formed. Thus, the definition of regeneration hinges on
the methodology used for its assessment and appears to
fall short when more advanced molecular techniques are
used. Perhaps a more conservative term to be used to
describe this procedure is guided endodontic repair
(GER). A repaired tissue that promotes the resolution of
disease and reestablishment of some or all of the original
tissue functions should be a desirable goal. The dental
pulp capacity of repair seen in direct and indirect pulp
capping procedures is absent once the pulp completely
succumbs to infection or trauma. In these cases, clini-
cians using the knowledge in regenerative endodontics
are able to guide endodontic repair, attaining the desir-
able patient- and clinician-centered outcomes. Clinicians
and scientists working in tandem striving to achieve the
scientist-based outcome of true regeneration are creating
tangible advances in endodontic care, departing from a
materials-based to a biologically based approach.
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CONCLUSIONS
Substantial advances in regenerative endodontics are
allowing for a better understanding of a multitude of
factors that govern stem cell–mediated regeneration and
repair of the damaged pulp-dentin complex. REPs are
valuable adjuvants to the treatment and retention of
immature teeth with pulp necrosis with an otherwise
poor prognosis. Despite the clinical success of these
procedures, they appear to promote a GER process
rather than a true regeneration of physiological-like tis-
sue. For greater regenerative potential to be met, in-
vestigators must perform much more research and
development. Translational research is crucial in making
these procedures more predictable while pushing the
boundaries of future procedures that are likely to involve
the direct clinical manipulation of scaffolds, growth
factors, and stem cells. n
Dr. Diogenes is an associate professor, Department of Endodontics,
University of Texas Health Science Center at San Antonio, 7703 Floyd Curl
Dr., San Antonio, TX 78229, e-mail diogenes@uthscsa.edu. Address corre-
spondence to Dr. Diogenes.
Dr. Ruparel is an assistant professor, Department of Endodontics, Uni-
versity of Texas Health Science Center at San Antonio, San Antonio, TX.
Dr. Shiloah is an adjunct professor, Department of Endodontics, Uni-
versity of Texas Health Science Center at San Antonio, San Antonio, TX.
Dr. Hargreaves is a professor and the chair, Department of Endodontics,
University of Texas Health Science Center at San Antonio, San Antonio, TX.
Disclosure. None of the authors reported any disclosures.
Endodontics is published in collaboration with the American Association
of Endodontists.
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