A Self-Powered Biodegradable Electroactive Conduit with Sustained NGF Release for Enhanced Peripheral Nerve Regeneration via Mitochondrial Bioenergetic Activation

The clinical translation of electroactive nerve conduits is often hindered by the trade-off between electrical performance and biodegradability, as well as the rapid clearance of neurotrophic factors which limits their ability to act in concert with long-term electrical stimulation. In this study, we engineered a fully biodegradable, self-powered multifunctional conduit by integrating piezoelectric poly( l -lactic acid) (PLLA) matrix with conductive reduced graphene oxide (rGO) within a flexible poly( l -lactide- co -ε-caprolactone) (PLCL) scaffold. This unique piezoelectric-conductive hybrid enabled efficient charge generation under mechanical stress and rapid signal transmission, creating an intrinsic electroactive microenvironment without external power sources. A polydopamine coating was further employed to enable sustained NGF release, extending the bioactive window of the scaffold. In vitro cell experiments demonstrated this dual-electroactive platform synergistically enhanced Schwann cells myelination, and promoted neuronal differentiation and neurite outgrowth in PC12 cells. Mechanistically, the in situ generated electrical activity amplified NGF-induced intracellular Ca 2+ influx, leading to sustained mitochondrial activation and elevated ATP production, providing the bioenergetic foundation for enhanced regeneration. In a rat 10 mm sciatic nerve defect model, the conduit effectively accelerated functional recovery, reduced muscle atrophy, and promoted axonal regeneration and remyelination, achieving outcomes comparable to autografts. This work demonstrated that maintaining sustained copresence of self-generated electrical cues and neurotrophic support within a fully resorbable platform effectively enhances peripheral nerve regeneration.