Engineered PVDF/PLCL/PEDOT Dual Electroactive Nerve Conduit to Mediate Peripheral Nerve Regeneration by Modulating the Immune Microenvironment

Abstract Electroactive materials are increasingly recognized for their efficacy in promoting the repair of peripheral nerve injury. However, the mechanism by which electroactive materials promote peripheral nerve regeneration by modulating the immune microenvironment remains incompletely explored. In this study, a PVDF/PLCL/PEDOT artificial peripheral nerve conduit with dual electroactivity by integrating piezoelectric properties and electrical conductivity is constructed. The electroactive conduit exhibited excellent spontaneous electrical and conductive properties, superior suture resistance and anti‐twisting properties. Detailed in vitro cell experiments and in vivo animal experiments are conducted, revealing that the electroactive nerve conduit can effectively promote rat sciatic nerve regeneration while facilitating reconstruction of both nerve conduction function and motor function. Furthermore, the underlying mechanism in depth is investigated and found that the electroactive material can regulate the immune microenvironment by activating the PI3K/AKT‐Nrf2 signaling pathway, thereby promoting macrophage polarization toward M2 anti‐inflammatory phenotype. This subsequently facilitated Schwann cell recruitment and myelin formation through mediation of the macrophage paracrine system. Importantly, blocking immune signaling pathways diminished the effectiveness of the electroactive nerve conduit in promoting nerve repair. The work elucidated how electroactive materials modulate immune microenvironment to positively impact peripheral nerve repair, highlighting the critical role of immune modulation in peripheral nerve repair.