This document summarizes the outcomes of regenerative endodontic procedures. It finds that regenerative endodontic procedures (REPs) are generally more successful at resolving symptoms of apical periodontitis compared to apexification. REPs also typically result in greater increases in root length and thickness compared to apexification. However, the degree of additional root development from REPs can vary significantly depending on factors like the cause of pulp necrosis. Long-term survival rates of teeth treated with REPs or apexification are still unclear due to a lack of large, long-term studies. Return of pulp vitality is achieved in around half of REP cases.

1. REGENERATIVE ENDODONTIC
PROCEDURES: CLINICAL
OUTCOMES
(JOURNAL CLUB)
Dr.Tinet Mary Augustine. BDS,MDS
Pediatric Dentist
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2. ARTICLE
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3. INTRODUCTION
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4. AIM
• Use of biologic-based procedures to arrest
the disease process, preventing its recurrence
while favoring the repair or replacement of
damaged structures of the pulp-dentin
complex.
DR.TINET MARY AUGUSTINE.MDS 4

5. DIFFERENT TERMS BUT
THE SAME CONCEPT
Revascularization
(Iwaya 2001)
Guided tissue
regeneration
Regenerative endodontic
procedure
AAE 2007
Revitalization
(Torabinejad 2011,Wang
2010,ESF2016)
Maturogenesis
(Aggarwal V 2012 )
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6. THE CLINICAL PROBLEM
TREATMENT OPTION-
APEXIFICATION(CVEK 1992),IMPLANTS(HEING DG 2006), REP(SAOUD 2016)
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7. • Self revascularization concept after severe
trauma(Kling M Cvek M 1986)
• Supported by Anderson in series of study in
1995,and 1996
REVASCULARIZATION
VS
REGENERATION
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8. DENTAL TISSUE DERIVED
MESENCHYMAL STEM CELLS
Mature teeth-Cherpa V 2015, But Decrease with age-Iohara 2014
Aged MSC-RejuvinationDR.TINET MARY AUGUSTINE.MDS 8

9. ROOT DEVELOPMENT AND APICAL
DIAMETER CONTROVERSY
0.1mm Kling M ,Cvek M-1986,
0.3mm Laurey WG 2013
Chepra 2015-MSC transfer without apical widening in mature teeth
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10. ETIOLOGY OF PULP NECROSIS
IN IMMATURE TEETH
TRAUMA
Robertson, Anderson-35% 1996
Intrusion &avulsion- Anderson
1995,2006
Combination-Luridsen 2012
HERS-Saoud TM-2014
CARIES
CONGENITAL DEFECTS
Dens evaginatus or invaginatus 33%-Diogenes A2013,Levitan ME
2006
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11. COMMON FEATURES OF REGENERATIVE
ENDODONTIC PROCEDURES FOR THE
TREATMENT OF IMMATURE TEETH
WITH PULPAL NECROSIS
1. Disinfection
2. Recruitment of MSCs and establishment of a
scaffold
3. Placement of a coronal barrier and restoration
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12. DISINFECTION
Stem cell conductive enviornment- Diogenes
2014
Survival and differentiation
AAE and EES 2016-Chemical disinfection
NAOCL,EDTA,CHX
TAP,DAP,CA(OH)2
High conc.Naocl – Galler 2015
*EDTA- Avivi Arber -2011
Undiluted TAP,DAP is potent while
Full strength Ca(OH)2 or 1mg/ml TAP/DAP is
beneficial
( Ruparel2012, Althumairy 2014)
1.5% NaOCl followed by 17% EDTA and using either 1 mg/mL TAP or DAP or Ca(OH)2 is
recommended.
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13. DR.TINET MARY AUGUSTINE.MDS 13

14. RECRUITMENT OF APICAL
MESENCHYMAL STEM CELLS AND
ESTABLISHMENT OF A SCAFFOLD
Blood Clot – Nygard Ostby
1961
Blood Clot As A Scaffold-
Lovelace 2011
Other Scaffolds
PRP( Torabinejad 2011)
,PRF( Shivashankar 2012)
Injectable scaffolds
impregnated with FDG-
Nagy 2014
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15. PLACEMENT OF A CORONAL
BARRIER AND RESTORATION
SAFE ZONE BARRIER
promote the differentiation of MSCs into an
odontoblastlike phenotype and allow proliferation of
MSCs. Laurent P 2012
“Safe zone” and “biological seal”
Bioactive “coronal plug” using promineralizing
dental materials, such as MTA or Biodentin
Kontakiotis 2015
Without seal is also reported
Discolouration
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16. CLINICAL OUTCOMES
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17. PRIMARY TREATMENT GOAL-
Resolution of apical periodontitis
Promote healing of the diseased tissues,
prevention of disease relapse, and patient well-
being (patient centered outcomes)
Diogenes a 2016
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18. Retrospective study aimed to directly compare the
clinical outcomes of apexification and REP under
standardized protocols.
Apexification with the use of MTA or the long-term
use of calcium hydroxide.
Resolution of the disease process (no pain,
swelling, or sinus tracts) was found in 100% of the
REPs, 95% of the MTA apexification, and 77% of
calcium hydroxide apexification cases.
JERUPHAN T 2012 DR.TINET MARY AUGUSTINE.MDS 18

19. A retrospective study conducted without any
standardization of treatment protocols
Result found REPs to promote healing in 79% of
patients treated, whereas apexification procedures
promoted healing in 100% of the patients; this
difference was found not to be significant.
Alobaid as 2014
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20. A prospective study suggested- both MTA
apexification and REPs were found to promote
healing in 100% of all patients.
Nagy AA 2014
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21. • Further evidence of successful outcomes can be
found in case series and retrospective patient
cohort studies.
• Despite significant variations in etiology and
inclusion and exclusion criteria, these studies
demonstrate that on average both procedures
successfully resolve the signs and symptoms of
the disease in approximately 90% of patients.
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22. SECONDARY TREATMENT
GOAL-Root development
• Root development is considered a secondary
goal of REPs because it is expected to
increase resistance to fracture and tooth
survival
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23. An objective dependent measure of root
development to compare radiographic root
development between apexification procedures (n
5 40) and REPs (n 5 48).
Result reporting that teeth treated with REP
showed significantly greater percentage increase in
root length (14.9%) compared with teeth treated by
either MTA apexification (6.1%) or calcium
hydroxide apexification (0.4%).
Bose R in 2009
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24. • Findings of Bose R have been confirmed by
Jeeruphan and colleagues in 2012 using a similar
quantitative technique.
• They reported that the revascularization
protocol also produced significantly greater
percentage increases in root width (28.2%)
compared with teeth treated by either MTA
apexification (0.0%) or calcium hydroxide
apexification (1.52%).
Jeeruphan and colleagues 2012
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25. • A prospective randomized clinical trial that
compared 2 different protocols of REPs with MTA
apexification procedures .
• The result suggested that regenerative procedures
promoted an average increase of 12% in root
thickness and a 50% decrease in apical diameter
(apical closure), whereas apexification procedures
demonstrated no change during the 18-month
observation period.
Nagy AA in 2014
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26. A recent retrospective study reported that degree
of root development was highly varied and
unpredictable.
This discrepancy is likely due to the greater number
of included cases with trauma as the etiology for
pulpal necrosis, and the relatively small sample size
Alobaid as 2014
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27. • Evidence that REP promote increase in
radiographic root development in most cases,
but not all. The factors that influence this lack
of response could include
The persistence of bacterial biofilms or antigens
The nature of the etiology
Delay in treatment
The impact of disinfection agents on the
creation of a microenvironment conducive to
regeneration.
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28. • Unfortunately, far less is known regarding the
long-term survival of immature teeth treated
with either apexification or REPs.
Salehrabi R in 2004
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29. • Comparison of the survival of teeth treated with
either REPs or Apexification procedures with
calcium hydroxide or placement of an MTA apical
plug showed a survival of teeth treated with REPs
(100% of teeth survived) during the follow-up
period of the study (18 months) and was
significantly greater than that of teeth treated with
calcium hydroxide (77%), but not different from
teeth treated with an MTA apical plug (95%).
Jeeruphan t in 2012
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30. Prolonged use of calcium hydroxide can
significantly weaken teeth, increasing their
susceptibility to fracture.
Cvek M 1992 and Andreasen JO 2002 that
Factors affecting the long-term survival of
these teeth require further investigation
with studies using appropriate sample sizes
and follow-up.
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31. TERTIARY TREATMENT GOAL
Return of pulp vitality
• Diogenes A 2013 suggested 50% of all
published REPs
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32. • The presence of functional nociceptors following
REPs suggests that apically positioned free nerve
endings of primary afferents are guided into the
canal by specific neuroattractant and neuro-
repelling molecules chemical signals.
• Similar to the targeting of axons from trigeminal
sensory neurons that accumulate forming a plexus
beneath the tooth organ and dental follicle, but do
not enter the apical papilla until late bell stage and
during the eruption process.
• Fried k 2000
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33. • SCAP during tooth development express these
molecules at the earliest stages of tooth
development, and have been implicated and the
primary cell type guiding axonal navigation and
targeting into the developing tooth.
*The same stem cells of the apical papilla SCAP)
are believed to be a prominent cell type in REPs in
immature teeth.
• Diogenes A 2013,Huang GT 2008
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34. • A recent study to investigate whether
postdevelopment SCAP could direct trigeminal
neuronal targeting and innervation
demonstrated that SCAP harvested from an
erupted third molar mediated robust axonal
growth and targeting through the release of
brain-derived neurotrophic factor (BDNF)
• De Almeida 2014
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35. • A complete pulpal regeneration, including
innervation, was achieved in dogs with the
use of autologous transplantation of DPSCs
Iohara K 2011
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36. • These SCAP cells were found to express high
levels of BDNF compared with adipose and
bone marrow MSCs.
• Ishizaka 2013
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37. • Collectively, these findings support the hypothesis
that MSCs transferred into the root canal space
during REPs are likely important in the recruitment
of apical primary afferent fibers through a specific
mechanism of postnatal axonal targeting.
• The exact mechanism warrants further
investigation.
DR.TINET MARY AUGUSTINE.MDS 37

38. • Nonetheless, the presence of innervation suggests
the presence of a vital tissue that is immune-
competent due to the intimate association of
innervation with blood vessels and the immune
system.
• It also suggests the recovery of nociception that is
crucial for the detection of actual or potential
injury to the tooth organ.
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39. REPAIR OR REGENERATION
• Debate on the use of the term “regeneration” as
newly formed tissue does not resemble the lost
pulp-dentin complex.
• To date, even in sophisticated animal models,
tissues formed closely resemble the native dental
pulp but true odontoblasts are missing; instead,
mineralizing cells called “odontoblastlike cells” are
formed.
Ioharak 2011,Ishizaka R 2012DR.TINET MARY AUGUSTINE.MDS 39

40. IDEAL TERMINOLOGY
• Guided-endodontic repair (GER);
• A repaired tissue that promotes resolution of
the disease and reestablishment of some or
all the original tissue functions should be an
acceptable goal.
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41. DIFFERENT PERSPECTIVE
• From a patient-centered outcome perspective,
shortcomings in histologic regeneration do not
represent a failure.(Diogenes 2016
• from a clinician perspective, a treated tooth that is
asymptomatic, without any signs of disease and is
functional should be considered a
success.(Diogenes 2016)
• From a scientific perspective, the lack of control of
the tissues formed represents the status of the
current procedures.
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42. CONCLUSION
• Dental pulp has the capacity to repair and
successfully self-revascularize after infection
or trauma.
• Formation of a reparative tissue displaying
regaining of lost physiologic functions, such
as vascularity, nociception, and mineral
tissue deposition.
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43. • Clinical application of tissue engineering
principles with the goal of achieving
maximum disinfection while creating the
most conducive environment for stem cells to
direct the repair and regeneration of the
target tissue.
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44. • Future developments : place elaborate
scaffolds with chemotactic agents to promote
the repopulation of the root canal system to
achieve the desired histologic evidence of
“regeneration.”
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45. IMPORTANCE IN PEDIATRIC
DENTISTRY
TRAUMA
CARIES
DEVELOPMENTAL
ANOMALIES
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46. CRITICAL EVALUATION
• Explained the goals clearly.
• Gives an understanding of the various clinical
outcomes of regenerative procedure.
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47. CROSS REFERENCE
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48. Dentin
secreation and
odontoblastic
activity
P 38 gene
MAPK signalling
–cellular
differentiation
TGGbeta 1 –
odontoblastic
differentiation
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49. Early
Cell
mobilization
Late
Cell
differentiation
Scaffolds
Collagen
matrix
Microsphere
Shell
microsphere DR.TINET MARY AUGUSTINE.MDS 49

50. HISTORIC BACKGROUND
CLINICAL PROTOCOLS
MEDICAMENTS
ONE VISIT RET(MC CABE 2015,CHANIOTIS 2016)OUTCOME
SUCCESS RATE(91%)
MANAGEMENT OF FAILED RET
FOLLOW UP(LONG TERM)
CELL HOMING STUDIES.
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51. THANK YOU
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