BiomimeticMultichannel 3D MXene Nanofiber Spongesfor Peripheral Nerve Regeneration

Abstract Nerve guidance conduits play a critical role in bridging nerve gaps and facilitating neural repair. Recent advances highlight that structural optimization and functional enhancement can further enhance the regenerative outcomes. Herein, inspired by the structural features of celery stalks and native nerves, we propose a biomimetic multichannel three-dimensional (3D) MXene nanofiber sponge scaffold for reconstructing large-gap peripheral nerve defects. The scaffold integrates MXene-loaded sacrificial alginate microfibers, a gas-foamed 3D porous nanofiber sponge, and a gelatin methacryloyl hydrogel encapsulating neurotrophic and angiogenic factors. The biomimetic multichannel structure was obtained by sacrificing the alginate microfibers, during which MXene nanosheets were released and deposited onto the channels. Benefiting from the conductive microchannels, the 3D sponge network, and the bioactive hydrogel, the scaffold potently induced the differentiation of rat pheochromocytoma cells and supported endothelial tube formation. Moreover, the scaffold significantly enhanced nerve regeneration and functional motor recovery in rat long-gap nerve defect models. These findings demonstrate a potential strategy for the regeneration of peripheral nerve defects.