Stepwise Regulation of Cellular Oxidative Stress via Conductive‐Piezoelectric Integrated Microstructured Conduits for Enhanced Nerve Regeneration

Peripheral nerve injury (PNI) poses significant challenges due to the complex structure and regenerative microenvironment of peripheral nerves, which limit self-repair capabilities. Artificial nerve conduits have been widely used for nerve repair. Here, a conductive-piezoelectric integrated microstructured conduit is designed, using poly(lactic glycolic acid) (PLGA) and poly(vinylidene fluoride) (PVDF) via electrostatic spinning to obtain an implantable, biodegradable piezoelectric nanofibrous membrane. This membrane is further enhanced with a reduced graphene oxide/methacrylated gelatin (rGO/GelMA) gel, which synergistically promotes peripheral nerve repair. In vitro assessments reveal that the microgroove surface pattern of the conduit effectively stimulated the directional migration of cells. Moreover, using a rat sciatic nerve injury model, rGO is demonstrated to significantly modulate cellular oxidative stress, thereby facilitating nerve repair. Additionally, mild electrical stimulation induced by low-intensity pulsed ultrasound (LIPUS) is found to enhance the recovery of motor function. These findings demonstrate the multifaceted benefits of the rGO/GelMA@PVGA composite conduit, which integrates physical guidance, oxidative stress inhibition, and ultrasound-activated electrical stimulation, providing an unprecedented multimodal synergistic strategy with great potential for clinical treatment of peripheral nerve injury.