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.
Living biomaterials directly couple with live cells to synthesize functional molecules and respond to dynamic environments, allowing the design, construction and application of next generation composite materials. Improving the coordination and communication between artificial materials and living cells is essential. In this study, collagen self-assembly and micro-sol electrospinning techniques are used to prepare oriented living fiber bundles that can increase the transplantation rate of stem cells in the early stages of inflammation, indirectly enhancing the dynamic regulation of stem cells during inflammation. Additionally, brain-derived neurotrophic factor (BDNF) contained in the fiber can improve the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neurons once the inflammatory storm subsides. The living oriented fiber bundles fully simulate the 3D structure of the central nervous system, activate integrin β 1, promote the growth and adhesion of stem cells in the acute stage of inflammation, upregulate anti-inflammatory genes by more than twofold via BMSCs in response to inflammation, and stably release BDNF for up to 4 weeks post-inflammation storm subsidence. Finally, the BDNF induces the differentiation of BMSCs to neurons by enhancing the expression of neural-related genes, which enables the recovery of neurological functions in the later stages of spinal cord injury.
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