Microenvironment-Responsive Injectable Conductive Hydrogel for Spinal Cord Injury Repair

Abstract

Spinal cord injury (SCI) represents a severe neurological condition often coupled with a drastic secondary inflammatory response, which further exacerbates the damage in most cases. Due to their unique electrical and mechanical compatibilities with the spinal cord, the utilization of conductive hydrogels through injection for SCI repair, particularly in scenarios involving non-uniform and large gaps, has emerged as a promising approach. Herein, leveraging the acidic microenvironment characteristic of acute SCI sites, an injectable conductive hydrogel with pH-responsive immunoregulation is engineered for SCI repair. Based on the dynamic Schiff base chemistry and covalent photo-crosslinking, this composite hydrogel, composed of gelatin methacryloyl, oxidized dextran, and MoS2, exhibits adjustable mechanical and conductive properties, enabling a customized match with the natural spinal cord's attributes. Additionally, the incorporation of Wnt5a and its selective release in acidic conditions prompt the immediate suppression of inflammatory factors and enhances neural differentiation and regeneration. In the 2-mm hemisection mouse SCI model, the optimized conductive hydrogel can effectively bridge the injury gap, establish nerve connections and signal, mitigate inflammatory response, and promoted recovery of mobility. This novel injectable conductive hydrogel system offers a promising advance in therapeutic materials for SCI repair.