A Multifunctional Hydrogel Conduit Loaded with miR-29a@Cu-MBG-NH2 for Potential Applications in Peripheral Nerve Repair

Peripheral nerve injury frequently occurs alongside vascular injury due to the incorporation of vascular tissue within the nerve bundle. During the repair process of peripheral nerve injuries, the concurrent regeneration of capillaries within the nerve bundles is crucial for facilitating nerve regeneration. However, current studies often overlook the regeneration of blood vessels in nerve bundles when designing nerve repair scaffolds, leading to suboptimal nerve regeneration outcomes. To address this limitation, amino-modified Cu-doped mesoporous bioactive glass (Cu-MBG) was developed as a nanodelivery carrier for miR-29a to construct miR-29a@Cu-MBG nanoparticles, which exhibit dual functionality in promoting nerve regeneration and inducing vascular regeneration. Subsequently, miR-29a@Cu-MBG was incorporated into a CS/GelMA hydrogel to create an engineered multifunctional nerve conduit through the ionic cross-linking of chitosan and the optical cross-linking of GelMA, which demonstrated excellent mechanical properties and biocompatibility. In vitro cell experiments indicated that the sustained release of miR-29a@Cu-MBG from the conduit effectively delivered miR-29a into PC12 cells, leading to the upregulation of nerve regeneration-associated genes (GAP-43 and NF-200) and the outgrowth of neurite. Additionally, Cu-MBG was found to enhance the migration of HUVECs and upregulate genes related to angiogenesis (HIF-α, ANG, eNOS, and KDR), promoting the tube formation of HUVECs. These findings offer a perspective for the design of nerve conduits capable of promoting both nerve and vascular regeneration.