A porcine acellular nerve matrix membrane with dual neurotrophic and immunomodulatory functions accelerates peripheral nerve regeneration by coordinating Schwann cell activation and remyelination

Repairing peripheral nerve injuries remains challenging because it requires biomaterials that can simultaneously modulate the adverse immune microenvironment and provide a bionic niche with integrated physical and biochemical cues. To address this, we developed a porcine sciatic nerve-derived acellular matrix membrane (SNCM) that uniquely preserved a native-like ensemble of extracellular matrix components (e.g., laminin, fibronectin, sulfated glycosaminoglycans) and endogenous neurotrophic factors. The SNCM exhibited superior physicochemical properties, including controlled degradation, enhanced mechanical robustness, high hydration, and favorable hemocompatibility. It also demonstrated potent immunomodulatory activity by efficiently scavenging reactive oxygen and nitrogen species. In vitro, SNCM specifically promoted neuronal differentiation of PC12 cells and enhanced Schwann cell migration, proliferation, and pro-regenerative phenotype activation. In a rabbit tibial nerve injury model, SNCM application significantly reduced the incidence of severe perianastomotic adhesion and neuroma formation (with no severe adhesion cases detected in the SNCM cohort), substantially improved functional recovery (evidenced by increased muscle wet weight ratio), and facilitated structural regeneration characterized by orderly axonal regrowth, coordinated Schwann cell activity, and robust remyelination, achieving a near-complete myelinated nerve fiber regeneration rate. By synergistically integrating structural, neurotrophic, and immunomodulatory functions into a single biomimetic platform, SNCM actively orchestrates a pro-regenerative microenvironment, positioning it as a highly competitive and clinically translatable strategy for advanced nerve repair.