Self-assembled silk fibroin injectable hydrogels based on layered double hydroxides for spinal cord injury repair

Summary

Spinal cord injury (SCI) hinders neural regeneration due to the pathological microenvironments with reduced Mg²⁺ levels, hypoxia, inflammation, and elevated reactive oxygen species (ROS). Here, we developed a bioactive metal ion-based injectable hydrogel for SCI treatment by integrating ultrathin and antioxidant MgMn-based layered double hydroxides (ULDH) with silk fibroin (SF), which facilitated the formation of a β-sheet structure. SF-ULDH hydrogels continuously scavenge ROS and release oxygen (O₂) through Mn³⁺ to alleviate oxidative stress and hypoxia. Impressively, SF-ULDH hydrogels effectively promoted PC12 cell growth and differentiation with the activation of supplemented Mg²⁺. Bulk RNA sequencing data demonstrated significant enrichment of various pathways, including the PI3K-Akt signaling pathway, HIF-1 signaling pathway, and axon regeneration pathway in the SF-ULDH group. Our findings underscore the importance of combined strategy by integrating bioactive metal ions into hydrogels to address the multifaceted complications of the pathological microenvironment, thereby enhancing SCI repair outcomes.