A printable blue-light photocurable gelatin methacryloyl/silk fibroin hydrogel loaded with salvianolic acid B for enhanced spinal cord repair.

Spinal cord injury (SCI) leads to severe neurological impairment, highlighting the critical need for effective regenerative treatments. While existing therapeutic strategies show limited capacity to promote axonal regeneration, we developed an innovative 3D-printable, blue-light photo-crosslinkable hydrogel system combining silk fibroin with gelatin methacryloyl (GelMA) and incorporating salvianolic acid B (Sal B). The engineered composite was fabricated via a denaturation-refolding protocol in which a denaturant unfolded silk β-sheets to promote rapid ion exchange and high-efficiency Sal B incorporation, yielding a denser network and improved encapsulation. In established rodent models of SCI, the Sal B loaded hydrogel significantly reduced neuroinflammatory responses and promoted functional restoration through dual mechanisms involving reactive oxygen species (ROS) suppression and PI3K/AKT pathway activation. Of particular significance, the hydrogel effectively induced M2 phenotype macrophage polarization, creating a favorable microenvironment for neural tissue repair. These results provide mechanistic evidence that Sal B incorporated GelMA/silk fibroin hydrogels represent a multifunctional, translationally promising platform for SCI repair.