Polyethylene Glycol-Mediated Axonal Fusion Promotes Early Sensory Recovery After Digital Nerve Injury: A Randomized Clinical Trial

Abstract

Background. Peripheral nerve repair is limited by Wallerian degeneration coupled with the slow and inconsistent rates of nerve regrowth. In more proximal injuries, delayed nerve regeneration can cause debilitating muscle atrophy. Topical application of polyethylene glycol (PEG) during neurorrhaphy facilitates the fusion of severed axonal membranes, immediately restoring action potentials across the coaptation site. In preclinical animal models, PEG-fusion resulted in remarkable early functional recovery. Methods. This is the first randomized clinical trial comparing functional outcomes between PEG-fusion and standard neurorrhaphy. Participants with digital nerve transections were followed up at 2 weeks, 1 month, and 3 months postoperatively. The primary outcome was assessed using the Medical Research Council Classification (MRCC) rating for sensory recovery at each timepoint. Semmes-Weinstein monofilaments and static two-point discrimination determined MRCC ratings. Postoperative quality of life was measured using the Michigan Hand Questionnaire (MHQ). Results. Forty-eight transected digital nerves (25 control, 23 PEG) across twenty-two patients were analyzed. PEG-fused nerves demonstrated significantly higher MRCC scores at 2 weeks (OR 16.95, 95% CI: 1.79 – 160.38, p = 0.008) and 1 month (OR 13.40, 95% CI: 1.64 – 109.77, p = 0.009). Participants in the PEG cohort also had significantly higher average MHQ scores at 2 weeks (Hodge’s g 1.28, 95% CI: 0.23 – 2.30, p = 0.0163) and 1 month (Hodge’s g 1.02, 95% CI: 0.04 – 1.99, p = 0.049). No participants had adverse events related to the study drug. Conclusion. PEG-fusion promotes early sensory recovery and improved patient well-being following peripheral nerve repair of digital nerves.