Neuroactive network tissue based on dual-factor neuroregenerative bioactive coating scaffolds and neural stem cells for spinal cord injury repair.

Spinal cord injury (SCI) results in sensory and motor dysfunction, with neuronal death, circuit disruption, and the inhibitory microenvironment serving as key limitations to effective treatment. In this study, we developed a neuroactive network tissue for SCI repair by immobilizing dual recombinant growth factors based on biomimetic mussel adhesive units onto an oriented electrospun nanofiber scaffold, and seeding neural stem cells (NSCs) onto the scaffold. This dual-factor system continuously stimulates and enhances the paracrine function of NSCs, promoting repair of the injury site. In the early stages, the neurorepair coating amplifies the paracrine effects of NSCs, alleviating oxidative stress and inflammation while inhibiting neuronal cell death. In the later stages, it facilitates neurogenesis, axon growth, and neural circuit restoration. Single-cell RNA sequencing further reveals that the treatment reduces immune cell activation, promotes the survival of neurons and oligodendrocytes, sequentially and multidimensionally improves the local microenvironment, and enhances tissue regeneration. Both in vitro and in vivo experiments confirms that the neural active network effectively reshapes the immune environment at the injury site, boosting cell differentiation and repair, and thus providing a comprehensive strategy for tissue regeneration.