Implantation of a functional TEMPO-hydrogel induces recovery from rat spinal cord transection through promoting nerve regeneration and protecting bladder tissue
Spinal cord injury is one of the most serious traumatic diseases. Current available clinical therapies are unable to provide effective recovery of nerve functions. Implantation of biomaterial scaffolds is a promising approach to bridge the damaged nerve tissue in absence of extracellular matrix. However, the treatments have been impaired by the increased generation of reactive oxygen species in the microenvironment of acute spinal cord injury. Efficient delivery of antioxidant and biocompatible materials and reagents has been a challenge. Herein, a novel hyaluronic acid (HA) hydrogel functionalized with the antioxidant compound 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) is fabricated for nerve tissue regeneration after serious spinal cord transection in rats. TEMPO is tethered onto HA chains to form HA-TEMPO through Schiff Base reaction between 4-Amino-TEMPO and aldehyde modified HA chains. The TEMPO-hydrogel is constructed with highly porous three-dimensional structure via the gelation between the residue aldehydes in HA-TEMPO and the amines in adipic dihydrazide modified HA. The functional TEMPO-hydrogel exhibits antioxidant effect in H2O2 simulated in vitro peroxidative microenvironment. Implantation of the functional hydrogel in vivo induces a significant motor function restoration, which could attributed to the effective functions of the TEMPO-hydrogel in tissue reconnection as well as nerve fiber regeneration of the central nervous spinal cord tissue. Importantly, the treatment of the TEMPO-hydrogel effectively protects the bladder tissue from neurogenic damages. Therefore, the functional TEMPO-hydrogel provides a promising strategy for therapies of central nervous system diseases through the antioxidant as well as lesion-bridging regulation of pathological microenvironment.