A nerve conduit optimizing the microenvironment for neurorepair in long-segment nerve injury using silk fibroin-MXene conductive nerve guide and IGF-1/GelMA hydrogel

Long-segment peripheral nerve injury (PNI) represents a significant global health challenge, often leading to sensory and motor deficits, neuropathic pain, and secondary complications. Early reconnection of injured nerves is essential for preserving function and minimizing sequelae. In this study, we present a novel Silk Fibroin-MXene (SF-MXene) pIGF1 GelMA Hydrogel Nerve Conduit as an effective solution to optimize the bio-electrical and cellular microenvironment, thereby accelerating nerve regeneration. Unlike standalone plasmid Insulin-like Growth Factor-1 (pIGF1) releasing conduits, which disrupt growth direction and attract non-neuronal repair cells that obstruct nerve elongation, this advanced conduit enhances directional nerve growth and myelination while facilitating efficient electrical signal transmission in PNI rats. In this multifunctional NGC, pIGF1 optimizes the cellular microenvironment by promoting Schwann cell proliferation and migration, while the conductive SF-MXene NGC supports spatially ordered distribution and accelerates nerve elongation. Additionally, the conduit sustains long-term RANKL upregulation, activating NF-κB signaling to drive Schwann cell differentiation into myelinating subtypes, thereby promoting efficient and durable myelination of regenerated nerves and facilitating effective electrical signal transmission. These findings underscore the potential of the Silk-MXene + pIGF1 Nerve Conduit as a promising strategy for long-segment nerve injury repair, with strong implications for future clinical applications.