Autograft Polarity on Functional Outcomes Following Experimental Peripheral Nerve Repair Surgery: A Systematic Review...

Background: Proximal-distal orientation of nerve autografts (graft polarity) is an important consideration in peripheral nerve repair, but the literature is inconsistent on whether reversing graft polarity improves regeneration. With these disparities, we aimed to systematically review the effect of forward (normal proximal-to-distal) vs. reversed graft orientation on peripheral nerve regeneration or functional outcomes. Methods: We conducted a comprehensive search of PubMed, Scopus, Cochrane Library, EMBASE, and Google Scholar (January 1978-August 2025) for studies comparing autograft polarity in nerve regeneration. Of 90 articles identified, 9 studies met inclusion criteria (comparative studies directly evaluating graft orientation). Data on nerve conduction and functional recovery outcomes were extracted, and random-effects meta-analyses (using Hedges' g standardized mean differences) were performed to compare forward vs. reversed graft orientation, with heterogeneity assessed by I² and τ². Results: The nine included studies (all in animals) assessed histological, morphometric, electrophysiological (e.g., nerve conduction velocity, action potential amplitude), behavioral and functional outcomes. Three of the nine studies reported a significant outcome difference favoring one graft orientation, whereas six studies found no significant difference. Meta-analysis of five studies reporting nerve conduction velocity found no overall difference between forward and reversed orientation (Hedges' g = -0.57, 95% confidence interval -1.52 to 0.37; p = 0.23; I² = 82.96%, τ² = 0.935). Conclusions: This meta-analysis provides the first quantitative synthesis of experimental evidence assessing the impact of nerve autograft orientation, revealing no consistent advantage of forward or reversed polarity on regeneration outcomes. Although based on limited and heterogeneous animal data, the findings clarify existing trends and highlight areas for further experimental and clinical research.