Bioinspired Multilayered Conductive Nerve Guidance Conduit Built on Hydrogels and Knitted Silk Fiber Sleeves for Peripheral Nerve Regeneration

Repairing long-gap peripheral nerve injuries remains challenging. The main obstacles lie in the donor site morbidity and size restriction for autologous nerve transplantation as well as the lack of biomimetic structures for conventional artificial nerve conduits. Inspired by the multilayer structures of nerve conduit, we here present a composite nerve guidance conduit to mimic the hierarchical structures and bioelectrical properties of the native nerves. The conduit integrates an outer silk fibroin (SF) knitted sleeve (KS) to provide mechanical support and structural mimicry of epineurium, an inner multichannel hydrogel composed of silk fibroin (SF) and gelatin methacrylate (GelMA) for cellular adhesion and neurotrophic factor release, and polypyrrole (PPy) for electroactive regulation. The SF/GelMA/Ppy/KS composite conduit exhibited degradability, conductivity, mechanical stability, directional structure, electrical conductivity, and both in vitro and in vivo biocompatibility. The transplantation of the composite nerve conduit achieved nerve regeneration and functional recovery of the long defect sciatic nerve in rats. Integrating a biomimetic structure with multifunctional biomaterials, this work offers a promising artificial nerve conduit for long-segment nerve regeneration.