Non-Cochrane · intervention · PM42288014

Association of Apical Maturity With Clinical and Biological Outcomes After Regenerative Endodontic Procedures: A Systematic Review and Meta-Analysis.

Zhan Shengnan, Yan Qiaoyi, Zhang Yunxia · International dental journal · 2026 · PubMed · doi:10.1016/j.identj.2026.109660

Findings

Population Permanent teeth (immature or mature) with necrotic pulps

8 findings

Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Complete apical closure rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Random-effects model (DerSimonian-Laird; primary)
Proportion 0.53 [0.36, 0.70]
GRADE not reported
4 studies · 196 participants
Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Pulp vitality recovery rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Random-effects model (DerSimonian-Laird; primary)
Proportion 0.21 [0.07, 0.49]
GRADE not reported
4 studies · 224 participants
Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Pulp vitality recovery rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Common-effect model
Proportion 0.32 [0.26, 0.39]
GRADE not reported
4 studies · 224 participants
Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Tooth survival rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Common-effect model
Unresolved: the two extractors disagree on this row.
Proportion 0.98 [0.96, 0.99]
GRADE not reported
9 studies · 453 participants
Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Tooth survival rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Random-effects model (DerSimonian-Laird; primary)
Proportion 0.98 [0.95, 0.99]
GRADE not reported
9 studies · 453 participants
Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Complete apical closure rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Common-effect model
Proportion 0.57 [0.50, 0.64]
GRADE not reported
4 studies · 196 participants
Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Clinical success rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Random-effects model (DerSimonian-Laird; primary)
Proportion 0.90 [0.83, 0.95]
GRADE not reported
10 studies · 496 participants
Regenerative endodontic procedures (blood clot, PRF, CaOH, TAP, MTA, FGF and others)None (single-arm proportions pooled across study arms)Clinical success rate
Follow-up 12 to 52 months · Clinical studies in Asia, North America, Europe and Africa · Common-effect model
Proportion 0.89 [0.86, 0.91]
GRADE not reported
10 studies · 496 participants

Included primary studies 10

Open in Studies
StudyYearAlso included byOutcomes it informs hereTrial data
Lin 2017
Regenerative Endodontics Versus Apexification in Immature Permanent Teeth with Apical Periodontitis: A Prospective Randomized Controlled…
PMID:28864219
20171 other reviewClinical success rate; Tooth survival rate; Complete apical closure ratenot extracted yet
Al-Qudah 2023
Outcome of Regenerative Endodontic Procedures in Nonvital Immature Permanent Teeth Using 2 Intracanal Medications: A Prospective…
PMID:37225036
2023this review onlyClinical success rate; Tooth survival rate; Complete apical closure rate; Pulp vitality recovery ratenot extracted yet
Arslan 2019
Regenerative Endodontic Procedures in Necrotic Mature Teeth with Periapical Radiolucencies: A Preliminary Randomized Clinical Study.
PMID:31155298
2019this review onlyClinical success rate; Tooth survival rate; Pulp vitality recovery ratenot extracted yet
Chan 2016
Longitudinal Cohort Study of Regenerative Endodontic Treatment for Immature Necrotic Permanent Teeth.
PMID:28110920
2017this review onlyClinical success rate; Tooth survival rate; Complete apical closure ratenot extracted yet
Estefan 2016
Influence of Age and Apical Diameter on the Success of Endodontic Regeneration Procedures.
PMID:27623497
2016this review onlyClinical success rate; Tooth survival ratenot extracted yet
Lu 2023
Treatment outcomes of regenerative endodontic procedures in nonvital mature permanent teeth: a retrospective study.
PMID:37875745
2023this review onlyClinical success rate; Tooth survival rate; Pulp vitality recovery ratenot extracted yet
Nagy 2014
Regenerative potential of immature permanent teeth with necrotic pulps after different regenerative protocols.
PMID:24461403
2014this review onlyClinical success rate; Tooth survival ratenot extracted yet
Sheng 2025
Outcome of regenerative endodontic procedures in delayed replanted immature permanent teeth with apical periodontitis: A retrospective…
PMID:39245892
2025this review onlyClinical success rate; Tooth survival rate; Complete apical closure ratenot extracted yet
Silujjai 2017
Treatment Outcomes of Apexification or Revascularization in Nonvital Immature Permanent Teeth: A Retrospective Study.
PMID:28132710
2017this review onlyClinical success ratenot extracted yet
Theekakul 2024
Mahidol Study 2: Treatment Outcomes and Prognostic Factors of Regenerative Endodontic Procedures in Immature Permanent Teeth.
PMID:39216625
2024this review onlyClinical success rate; Tooth survival rate; Pulp vitality recovery ratenot extracted yet

Overlap with other reviews

Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.

Review question

ElementPlanned (methods)Found (results)
PopulationImmature and mature permanent teeth with necrotic pulps undergoing REPs508 teeth in 10 studies; 8 studies immature teeth, 2 studies mature teeth; mean age 9.1 to 25.6 years
InterventionREPs: blood clot, PRF, TAP, CaOH, MTA, FGF and other regenerative materials; initial apical diameter as exposure for dose-responseREP (blood clot), REP mixed, CaOH, TAP, FGF, MTA, replantation (n=10 studies)
ComparisonConventional apexification (e.g., MTA) or comparisons among regenerative techniques; single-arm studies eligibleMTA apexification (2 studies), CaOH or TAP (2 studies), none in single-arm studies
OutcomesClinical success (primary); tooth survival, complete apical closure, pulp vitality recovery (secondary)Clinical success (496 teeth), survival (453), apical closure (196), pulp vitality recovery (224)
Study designsRCTs, prospective and retrospective cohort studies, case series of >=5 teeth4 RCTs, 3 retrospective cohorts, 1 prospective cohort, 1 longitudinal cohort, 1 case series
TimingNot specifiedFollow-up 12 to 52 months

AMSTAR 2 items

Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.

ItemExtractor AExtractor BAgree
1Research question includes PICO componentsYesYesyes
2Protocol established before the reviewcriticalNoNoyes
3Choice of study designs explainedNoNoyes
4Comprehensive literature searchcriticalPartial YesPartial Yesyes
5Study selection in duplicateYesYesyes
6Data extraction in duplicateYesYesyes
7List of excluded studies with reasonscriticalNoNoyes
8Included studies described in detailPartial YesPartial Yesyes
9Risk of bias assessed satisfactorilycriticalRCT: Yes · NRSI: Partial YesNRSI: Partial Yes · RCT: Yesno
10Funding of included studies reportedNoNoyes
11Appropriate meta-analysis methodscriticalRCT: No · NRSI: Partial YesNRSI: No · RCT: Nono
12Impact of risk of bias on the pooled resultsNoNoyes
13Risk of bias accounted for in interpretationcriticalNoNoyes
14Heterogeneity explainedYesYesyes
15Publication bias investigatedcriticalYesYesyes
16Conflicts of interest reportedYesYesyes
OverallCritically LowCritically Lowyes