Conductive Hydrogels with Topographical Geometry and Mechanical Robustness for Enhanced Peripheral Nerve Regeneration

Nerve guidance conduits (NGCs) emerge as a promising solution for nerve regeneration; however, conventional NGCs fail to fulfill the requirements for peripheral nerve regeneration, which are subjected to periodical yet vigorous stretching, bending, and compression. Here, we developed a fatigue-resistant conductive hydrogel-based NGC by integrating topographical geometry, enhanced electroactivity, and superior fatigue resistance within one unit. The hydrogel, consisting of a PVA matrix with PEDOT:PSS as a conductive filler, features a topographical alignment that promotes axonal growth and achieves a fatigue threshold over 500 J/m², making it well-suited for sciatic nerve repairing. Phase segregation of PEDOT chains enhances its electrical conductivity (>500 S/m) and mitigates the interfacial impedance mismatch, allowing for high-efficiency bioelectrical signal transmission. <i>In vivo</i> studies on a rat sciatic nerve injury model corroborate the accelerated peripheral nerve regeneration through improved motor function recovery and efficient electrophysiological signal transmission. These findings establish our hydrogel-based NGCs as a promising solution for high-efficiency nerve regeneration through the synergy of topographical, mechanical, and electrical engineering.