Construction of adhesive and bioactive silk fibroin hydrogel for treatment of spinal cord injury

Spinal cord injury (SCI) often causes severe and permanent disabilities due to the complexity of injury progression. The promising methods are generally based on tissue engineering technology using biocompatible hydrogels to achieve SCI repair. However, hydrogels are commonly incapable of close contact with the damaged spinal cord stumps and fail to support neural regeneration in SCI. Therefore, it is still a challenge to achieve stable contact with the transected nerve stumps and accelerate neural regeneration in the lesion microenvironment. Here, an in situ forming glycidyl methacrylated silk fibroin/ laminin-acrylate (SF-GMA/LM-AC) hydrogel was fabricated for SCI repair. The polymer chains formed a network quickly after ultraviolet (UV)-light trigger, in topological entanglement with the spinal cord, stitching the hydrogel and wet tissues together like a suture at the molecular scale. The SF-GMA/LM-AC hydrogel also provided a favorable environment for the growth of cells due to the incorporation of LM-AC. Compared with physical entrapment of LM, LM-AC immobilized in the hydrogel by covalent technology provided better microenvironments for neural stem cells (NSCs) growth. The repair of complete transection SCI in rats demonstrated that this hydrogel guided and promoted neural regeneration over 8 weeks, leading to hind limb locomotion recovery. This adhesive and bioactive SF-GMA/LM-AC hydrogel may open many opportunities in various therapeutic indications, including SCI. STATEMENT OF SIGNIFICANCE: Many materials have been developed for building transplanted scaffolds, but it is still a challenge to fabricate bioactive scaffolds and adhesion to wet tissues. In this study, we successfully developed an in situ forming SF-GMA/LM-AC hydrogel for SCI repair. This in situ forming hydrogel formed significant adhesion to the native spinal cord, stitching hydrogel and tissue together like a suture at the molecular scale. In addition, covalent immobilized LM-AC was used as the contact guidance biochemical cues for axonal outgrowth and had much better bioactive effects than physically entangled LM. Moreover, this universal strategy would open an avenue to fabricate adhesive and bioactive hydrogel for various disease treatments including SCI.