Enhanced spinal cord injury repair using exosomes and neural stem cell loaded water-memory hyperelastic sponge scaffold by reducing inflammatory response

Runquan Zheng¹Baoyang Hu¹Jiawei Li²Suode Li²Xuesong Yan²Xianhu Yue^2*Ning Zhang^3*Shiqing Feng^1*

• ¹Tianjin Medical University, Tianjin, China
• ²960th Hospital of the PLA, Jinan, Shandong Province, China
• ³Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong Province, China

Despite over 20 million patients worldwide suffer 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 restracted by low survival rates, inadequate rates of neuronal differentiation, and a lack of spatial specificity. In this study, to address the aforementioned challenges in NSCs transplantation. we integrated porous 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 silk fibroin 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 neuraonal 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. Additionally, immune-inflammatory assays revealed that this strategy facilitates the transformation of microglia into an anti-inflammatory phenotype, thereby mitigating local inflammation.