Nanofibrous Guidance Conduits with Multiple Gradient Cues for Spinal Cord Repair

Abstract Spinal cord injury (SCI) is a debilitating condition that leads to severe disabilities and imposes significant economic and social burdens. Current therapeutic strategies primarily focus on symptom management, with limited success in promoting full neurological recovery. In response to this challenge, the design of novel guidance conduits incorporating multiple gradient cues, inspired is reported by biological processes, to enhance spinal cord repair. These conduits are fabricated using electrospinning and masked coaxial electrospraying, a simple yet effective method that integrates topological, haptotactic, and chemotactic cues into a single scaffold. The synergy of these cues significantly promoted cell migration, neural stem cell differentiation into neurons, and axonal extension, resulting in substantial improvements in spinal cord regeneration and functional recovery in a rat model. Single‐nucleus RNA sequencing further demonstrated that the guidance conduit inhibited fibroblast proliferation, preserved microglial homeostasis, restored cellular proportions, and facilitated the regeneration of neuronal axons, dendrites, and synapses. This work presents an innovative, versatile platform for fabricating tissue scaffolds that integrate multiple gradient cues, offering a promising strategy for SCI treatment and broader tissue regeneration applications.