Regenerative agents versus autogenous bone graft for alveolar cleft reconstruction: a systematic review and network meta-analysis

Background: Autogenous iliac crest bone graft is the standard for alveolar cleft reconstruction, but donor-site morbidity has prompted interest in regenerative agents. This review compared and ranked these agents against autogenous bone and one another.Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for network meta-analyses, six databases were searched from January 2000 to June 2026 for controlled studies comparing a regenerative agent with autogenous bone graft. Risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials and the ROBINS-I tool; certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. A frequentist random-effects network meta-analysis used autogenous bone as the reference and P-scores to rank treatments for new bone formation, bone density, graft volume, and graft success.Results: Twenty-one studies (23 reports) were included. Platelet-rich fibrin (risk ratio [RR], 1.46; 95% confidence interval [CI], 1.07–2.01) and concentrated growth factor (RR, 1.21; 95% CI, 1.02–1.43) were superior to autograft for graft success; platelet-rich fibrin ranked first (P-score, 0.87) and exceeded recombinant human bone morphogenetic protein-2 (RR, 1.44; 95% CI, 1.04–1.99). In one trial, bone marrow aspirate concentrate increased graft volume (standardized mean difference, 2.36; 95% CI, 1.51–3.21). No agent increased new bone formation or bone density. Certainty was moderate for one comparison, low for six, and very low for nine.Conclusion: Autogenous bone remains the volumetric reference standard. The improvement in graft success with platelet-rich fibrin was supported by moderate-certainty evidence and persisted across all sensitivity analyses, including restriction to randomized evidence. The concentrated growth factor finding had low certainty, relied on one retrospective study, and did not persist when analyses were restricted to radiographic outcomes. Adequately powered randomized trials with standardized methods are needed.