Spinal Cord-Like Scaffold with Rapid Tissue Integration Enhanced Spinal Cord Nerve Repair.

Spinal cord injury (SCI) repair represents an immense challenge globally. Despite various beneficial strategies having been attempted for SCI repair, the ideal therapy has not yet been achieved. In this study, a multidimensional biomimetic spinal cord-like scaffold (MBSLS) is designed with a hierarchical structure and embryonic neurogenetic microenvironment and neural regeneration in SCI repair. MBSLS successfully regulated the neural differentiation of loaded neural stem cells (NSCs) and regenerated spinal cord-like tissue in vitro by promoting neurogenesis, gliogenesis, axonogenesis, axon ensheathment, synapse organization, and calcium homeostasis. Moreover, the NSC-loaded scaffold achieves exceptional SCI repair through highly efficient axonal regeneration and neural circuit reconstruction, which significantly improves the recovery of motor function, sensory function, and autonomic function in vivo. Importantly, the MBSLS scaffold achieves seamless integration with the host spinal cord in only 5 min, allowing early cell infiltration and repair. Finally, the feasibility of the minimally invasive implantation of human-sized MBSLS in a pig SCI model is confirmed, demonstrating its potential and prospects for clinical translation to treat SCI.