Neonatal Spinal-Cord-Like Scaffold with Hierarchical Structural and Neurogenetic Microenvironments for Spinal Cord Injury Repair

Spinal cord injury (SCI) repair has been a great challenge worldwide because of its complex regeneration mechanisms and limited self-healing. The biomimetic construction of a bioactive scaffold represents a promising direction for SCI repair. Inspired by the efficient self-healing properties of the neonatal spinal cord, this study developed a neonatal spinal-cord-like scaffold (NSLS) aimed at regulating SCI repair at different stages. The NSLS features a neonatal spinal cord matrix, multilevel biomimetic structures, and matching mechanical strength via personalized laser processing and dual-network cross-linking. The microenvironments of the NSLS activate energy metabolism, synaptic formation, and the gliogenesis of neural stem cells (NSCs). Notably, the NSLS could achieve rapid hemostasis and integration with the host spinal cord, facilitating nutrient infiltration and establishing a stable connection in the early stage. Furthermore, NSCs loaded with NSLS (NSLT) promoted nerve repair by promoting microglial M2 polarization to decrease local inflammatory responses in the intermediate stage. Finally, axons grow directionally within the channels and form new connections to enhance neural repair and functional recovery in the late stage. Therefore, NSLT could significantly enhance nerve regeneration and functional recovery after SCI via stage-specific regulation.