Photocrosslinkable Dexamethasone-Loaded GelMA Hydrogel for Peripheral Nerve Injury: Mechanical Behaviour and Anti-Adhesion Effect

Peripheral nerve adhesion after surgical injury severely hinders functional nerve regeneration, leading to pain and neurological dysfunction. In this study, we developed a photocrosslinkable methacrylated gelatin (GelMA)-based hydrogel membrane that locally releases dexamethasone to simultaneously prevent adhesion and suppress inflammation. GelMA, synthesized by reacting gelatin with methacrylic anhydride, formed a stable crosslinked network, as confirmed by FT-IR spectroscopy and rheological analysis. Cytocompatibility assays showed that both GelMA and Dexa-GelMA hydrogels were non-cytotoxic to neuronal and fibroblast cell lines. In a Sprague-Dawley (SD) rat sciatic nerve injury model, implantation of the Dexa-GelMA hydrogel significantly reduced perineural adhesion and inflammation compared with the untreated control. Western blot analysis showed an approximately 80% reduction in ED-1 expression, indicating suppression of macrophage activation. Overall, the Dexa-GelMA hydrogel provides a biocompatible, multifunctional platform that integrates physical barrier function with anti-inflammatory drug delivery, showing strong potential for preventing postoperative nerve adhesion and modulating early inflammatory responses in a peripheral nerve injury model.