Multi-functional self-powered nanofiber conduit for peripheral nerve regeneration and muscle atrophy prevention.

Peripheral nerve injury (PNI) often leads to limited functional recovery in over 50% of patients, with current clinical strategies primarily relying on nerve grafts or conduits to bridge injury gaps. In the search of alternative solutions, self-powered biomaterials show significant potential in tissue engineering applications. This study designed a self-powered polycaprolactone/gelatin (PCL/gelatin) nanofiber conduit for sciatic nerve regeneration. The electrospun PCL/gelatin nanofiber conduit was characterized for its self-powering capability, mechanical strength, biocompatibility, and degradability. Functionalization of the nanofiber conduit with conductive polypyrrole (PPy) nanoparticles loaded with nonsteroidal anti-inflammatory drugs (NSAIDs) enhanced anti-inflammatory and antioxidative effects and helped prevent muscle atrophy. Furthermore, the incorporation of conductive polymers reduced polarization cancellation and enabled the controlled release of NSAIDs through exercise-induced mechanical stimulation of the nanofiber conduit. Transcriptomic analyses confirmed that the nanofiber conduit promoted peripheral nerve regeneration and inhibited apoptosis by activating insulin signaling.