Coptis chinensis -derived nanovesicle-loaded biodegradable hydrogel for preventing post-laminectomy epidural fibrosis

Post-laminectomy epidural fibrosis (PLEF) is a major contributor to failed back surgery syndrome, yet current preventive strategies remain unsatisfactory. Here, we engineered an injectable, biodegradable methacrylated hyaluronic acid-phenylboronic acid (HAMA-PBA) hydrogel incorporating Coptis chinensis-derived nanovesicles (CCNVs) for localized PLEF prevention. Characterization confirmed the successful isolation of nanoscale CCNVs and their uniform three-dimensional distribution within the hydrogel matrix. In vitro, the CCNVs-loaded hydrogel significantly suppressed L929 fibroblast proliferation and migration, primarily by inhibiting the TGF-[Formula: see text]/Smad2 signaling pathway. In a rat laminectomy model, local application of the HAMA-PBA@CCNVs hydrogel markedly reduced epidural scar adhesion and fibrous tissue formation. Furthermore, systemic safety and excellent biocompatibility were confirmed across major organs. Overall, this CCNVs-loaded hydrogel provides a safe, targeted, and effective nanobiotechnology-based strategy to prevent post-surgical epidural fibrosis and improve spinal surgery outcomes.Clinical trial number: not applicable.