Sonic hedgehog (SHH) has been shown to exert a protection on promoting the spinal cord injury (SCI) recovery, but it can’t remain with its biological activity and sustained release at the injury site for long-term application. Herein, fibrin scaffolds embedded with SHH-loaded
chitosan (CS) microspheres (SHH/CS) were synthesized and applied to provide protection and regeneration for complete transected spinal cord in rats. Characteristics of fibrin scaffolds embedded with SHH/CS microspheres, histological studies, immunohistochemistry staining, Western Blotting
and recovery of motor function were conducted after implantation, respectively. Result showed that SHH maintained its biological activity and continued to act at the injury site, and the fibrin scaffolds embedded with SHH/CS microspheres could protect neurons and reduce apoptosis in the in
vivo study, it also promoted some nerve fibers cross the spinal cord injury area. Moreover, the scaffolds improved partial motor function of double-hindlimb on a macro level. Overall, the fibrin scaffolds embedded with SHH/CS microspheres showed more satisfactory effect on nerve regeneration,
tissue cavities prevention and motor function improvement, compared to fibrin scaffolds with SHH directly encapsulated into or fibrin scaffolds alone.