Review Article| Volume 47, ISSUE 6, P873-882, June 2021

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Regenerative Endodontic Procedures for the Treatment of Necrotic Mature Teeth with Apical Periodontitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Published:March 31, 2021DOI:



      Regenerative endodontic procedures (REPs) are intended to repair and regenerate part of the pulp-dentin complex. The aim of this study was to systematically appraise the existing evidence on the effectiveness of REPs on mature teeth with pulp necrosis and apical periodontitis.


      Electronic database and hand searches were performed on 8 databases of published and unpublished literature from inception to January 3, 2021, for the identification of randomized controlled trials (RCTs) or prospective clinical trials. The related key words included “regenerative,” “pulp revascularization,” “revitalization procedure,” and “necrotic mature teeth.” A random effects meta-analysis was conducted assessing success as the main outcome treatment. Risk of bias was assessed through the Cochrane Risk of Bias 2.0 tool, and the quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.


      Of the 337 initial hits, 4 RCTs were eligible for inclusion, whereas 3 were included in the quantitative synthesis. Overall, there was no difference in the relative risk for a successful/unsuccessful treatment outcome between REPs or conventional treatment (3 studies, relative risk = 1.03; 95% confidence interval, 0.92–1.15; P = .61; heterogeneity I2 = 0.0%, P = .53; prediction interval = 0.51–2.09). Risk of bias ranged from low to raising some concerns, whereas the quality of the evidence was graded as moderate.


      Based on moderate-quality evidence, REPs appear as a viable treatment alternative for mature necrotic teeth with periapical lesions at present. Furthermore, well-designed RCTs might also provide confirmatory evidence in this respect while also framing a backbone for standardization of the therapeutic protocol of REPs.

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