Fabrication of In situ-Gelling Silk Fibroin-Based Biomimetic Hydrogel for Spinal Cord Repair

To develop a hydrogel scaffold for spinal cord repair with appropriate in situ gelation time, low modulus, and good biocompatibility, a horseradish peroxidase (HRP)-mediated, mildly crosslinked silk fibroin (SF)-based hydrogel was used as the matrix material. This SF-based composite hydrogel was further modified and tuned by incorporating tyramine (Tyr)-grafted hyaluronic acid (HA-Tyr). The effects of different HA-Tyr contents on the gelation time, compressive modulus, and cytocompatibility of SF-based composite hydrogels were investigated. Results indicated that higher HA-Tyr content led to shorter gelation time and higher compressive modulus of the composite hydrogels. The S8H2 hydrogel (volume ratio of SF to HA-Tyr is 8∶2) exhibited a gelation time highly consistent with the surgical implantation window, and its modulus also met the biomimetic requirements for spinal cord tissue. The proliferation capacity of mouse embryonic fibroblasts (NIH3T3) cultured on the hydrogel surfaces generally displayed an initial increase followed by a decrease with rising HA-Tyr content, with cells on the S8H2 hydrogel showing the highest viability. Considering the gelation time, compressive modulus, and cytocompatibility collectively, the S8H2 hydrogel demonstrated superior overall performance, showing promising potential for effective application in spinal cord injury repair.