Synergistic integration of flexible bioelectroactive nanofibrous conduits and electrical stimulation for accelerated peripheral nerve regeneration.

Repair of peripheral nerve injuries remains a major clinical challenge, motivating the development of bioelectroactive nerve guidance conduits (NGCs) capable of reconstructing the structural and electrophysiological microenvironment required for effective regeneration. Here, we report flexible bioelectroactive nerve guidance conduits (CPC-NGCs) that integrate mechanical compliance with efficient bioelectrical signal transmission, address challenges associated with the repair of peripheral nerve defects. These conduits are fabricated from chitosan, polyethylene oxide, and carbon nanotubes (CNTs) via electrospinning, forming a conductive nanofibrous network with a biomimetic fibrous architecture that supports peripheral nerve regeneration. By systematically regulating CNTs content, the hydrophilicity, conductivity, and mechanical properties of the conduits were optimized to achieve stable electrical performance and tissue adaptability. In vitro studies demonstrated that CPC-NGCs promoted PC12 cell viability, neurite extension, and neuronal differentiation. Electrical stimulation (ES) further enhanced neurite alignment and maturation-related marker expression. Moreover, the combination of CPC-NGCs and ES promoted Schwann cell elongation and maturation while modulating macrophage polarization toward a pro-regenerative M2 phenotype, thereby establishing a favorable microenvironment for nerve repair. In a 10 mm rat sciatic nerve defect model, electrically activated CPC-NGCs significantly enhanced axonal regeneration and remyelination, resulting in improved electrophysiological performance, sensory recovery, and motor functional restoration. Histological analyses further confirmed the reconstruction of structurally mature nerve tissue with reduced fibrosis. These findings demonstrate that the synergistic integration of biomimetic conductive conduits and electrical stimulation effectively promotes peripheral nerve regeneration through coordinated regulation of neuronal differentiation, Schwann cell maturation, and immune microenvironment remodeling.