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

objectivesTo systematically evaluate the outcomes of regenerative endodontic procedures (REPs) in teeth with varying degrees of root maturity and investigate how initial apical diameter influences clinical success, tooth survival, complete apical closure and pulp vitality recovery rates.

methodsElectronic databases, including PubMed, Embase, Web of Science, Scopus and the Cochrane Central Register of Controlled Trials, were systematically searched without date restrictions up to July 2025. Studies reporting REP outcomes (clinical success, tooth survival, complete apical closure and pulp vitality recovery) in immature and mature permanent teeth were deemed eligible. Eligibility criteria were structured using the population, intervention, comparison and outcome framework. Data extraction and quality assessment were independently performed by 2 reviewers using the Cochrane Risk of Bias tool 2 and the Newcastle-Ottawa scale. Meta-analysis, dose-response meta-analysis and trial sequential analysis were conducted to assess outcome stability and evidence robustness.

resultsTen studies involving 508 teeth were included in this review. The pooled clinical success rate was 90% (95% confidence interval [CI]: 83%-95%; n = 496 teeth), and the tooth survival rate was 98% (95% CI: 95%-99%; n = 453 teeth). Complete apical closure (53%, 95% CI: 36%-70%; n = 196) and pulp vitality recovery (21%, 95% CI: 7%-49%; n = 224) rates exhibited significant variability. Dose-response meta-analysis suggested that clinical success and tooth survival rates were relatively stable across apical diameters, whereas complete apical closure rates showed a possible negative association with increasing apical diameter. Trial sequential analysis suggested that the cumulative evidence for clinical success and tooth survival outcomes was relatively stable, though these findings should be interpreted in light of the heterogeneity and limited event counts across the included studies. Sensitivity analyses generally supported the robustness of the main findings.

conclusionsRegenerative endodontic procedures appear to achieve high rates of clinical success and tooth survival across varying degrees of root maturity. However, complete apical closure and pulp vitality recovery remain more variable and may be associated with initial apical maturity. Importantly, high clinical success and tooth survival rates do not necessarily indicate true pulp-dentin regeneration. These findings should be interpreted cautiously, given the heterogeneous protocols, mixed study designs and inconsistent outcome definitions of the included studies. Larger, well-designed, randomised controlled trials with standardised outcome definitions, uniform apical diameter measurement methods and longer follow-up periods are needed to refine these conclusions.