Architecture-engineered electrospinning cascade regulates spinal microenvironment to promote nerve regeneration.

The inflammatory cascade after spinal cord injury (SCI) causes necrotizing apoptosis of local stem cells, which limits nerve regeneration. Therefore, coordinating the inflammatory immune response and neural stem cell (NSC) functions is key to promoting the recovery of central nervous system function. In this study, a hydrogel "perfusion" system and electrospinning technology were integrated, and a "concrete" composite support for the repair of nerve injuries was built. The hydrogel's hydrophilic properties activated macrophage integrin receptors to mediate polarization into anti-inflammatory subtypes and caused a 10% increase in polarized M2 macrophages, thus reprogramming the SCI immune microenvironment. Programmed SDF-1α and BDNF release from the composite increased recruitment and neuronal differentiation of NSCs by approximately 4- and 2-fold, respectively. The fiber system regulated the SCI immune inflammatory microenvironment, recruited endogenous NSCs, promoted local blood vessel germination and maturation, and improved nerve function recovery in a rat SCI model. In conclusion, the engineering fiber composite improved the local inflammatory response. It promoted nerve regeneration through a hydrophilic programmed cytokine-delivery system, which further improved and supplemented the immune response mechanism regulated by the inherent properties of the biomaterial. The new fiber composite may serve as a new treatment approach for SCI. This article is protected by copyright. All rights reserved.