Transactional spinal cord injury repair using water-memory hyperelastic sponge scaffold with inflammatory regulated microenvironment

Despite over 20 × 106 patients worldwide suffering from spinal cord injury (SCI), there have been no significant breakthroughs in treatment to date. Although stem cell transplantation has demonstrated initial success, its therapeutic application is restricted by low survival rates, inadequate rates of neuronal differentiation, and a lack of spatial specificity. In this study, we aimed to address the aforementioned challenges in neural stem cell (NSC) transplantation by integrating porous silk fibroin (SF) scaffolds, exosomes, and NSCs to investigate their roles and efficacy in SCI repair. Initially, we screened for the optimal SF concentration to achieve mechanical biomimicry. Subsequently, we combined SF with exosomes and characterized their structural, compositional, elemental, hydrophilic, and shape memory properties, which demonstrated that the addition of exosomes did not significantly influence these characteristics. Furthermore, in vitro live/dead staining and gene expression analyses confirmed that the scaffold exhibits excellent biocompatibility and promotes neuronal differentiation. Finally, in vivo studies on SCI repair demonstrated that this strategy significantly enhances the recovery of motor and sensory functions as well as promotes axonal regeneration and reduces glial scar formation—ideal outcomes for neural repair. In addition, immune-inflammatory assays revealed that this strategy facilitates the transformation of microglia into an anti-inflammatory phenotype, thereby mitigating local inflammation.