A laminin-mimicking hydrogel as regenerative microenvironment for the repair of peripheral nerve injury

Extracellular matrix (ECM) components incorporated into biomaterials play a critical role in establishing a conducive microenvironment for tissue regeneration. When addressing peripheral injuries, an effective bio-scaffold not only necessitates ample ECM components but also offers a stable substrate throughout the regeneration process. Here, we present a UV gelation hydrogel characterized by excellent biocompatibility and a slow degradation rate. Through the copolymerization of self-assembling peptide RADA16 and laminin signal IKVAV, we enhance the extension of nerve fibers. Furthermore, the hydrogel network, formed by cross-linking RADA16-IKVAV with gelatin methacrylate (Gel-Ma), prolongs the mechanical property and degradation of the hydrogel, thereby fostering an environment conducive to nerve regeneration. In vivo studies corroborate the implanted hydrogel significantly facilitates axonal extension in 5 mm rat sciatic nerve defects. Notably, the hydrogel implantation repairs the injury site and achieves complete reconnection of the transected nerve, thereby substantially enhancing hindlimb locomotion function. These findings underscore the efficacy of laminin-mimicking hydrogel in promoting both morphological and functional recovery of injured sciatic nerves, holding promise for treating peripheral nerve defects.