Nano-fiber/net artificial bionic dura mater promotes neural stem cell differentiating by time sequence external-oral administration to repair spinal cord injury

<b>Rationale:</b> The inflammatory microenvironment and resulting neuronal loss following spinal cord injury (SCI) impede the repair process. Endogenous neural stem cells (NSCs), which are constrained by neuroinflammation and slow differentiation rates, are unable to effectively facilitate recovery. <b>Method:</b> In this study, coaxial electrospinning technology was employed to fabricate a nano-fiber/net artificial bionic dura mater (NABDM). This structure featured a core-shell structure, with nafamostat mesylate (NM) encapsulated in the outer layer of poly (lactic-co-glycolic acid) (PLGA) and neurotrophins-3 (NT3) encapsulated in the inner layer of poly (l-lactic acid) (PLLA). <b>Results:</b> The NABDM modifies the polarization direction of microglia <i>in vitro</i>, and promotes the differentiation of NSCs by activating the cGMP-PKG and cAMP signaling pathways. In a mouse SCI model, NABDM effectively reduces local neuroinflammation, accelerates the differentiation of endogenous NSCs, increases the number of mature neurons, and enhances motor, sensory, and autonomic nerve functions in mice. <b>Conclusion:</b> NABDM promotes the differentiation of NSCs and facilitates the repair of SCI in a time sequence external-oral way. This approach represents a rapid and effective new treatment method.