Novel enzymatically crosslinked chitosan hydrogels with free-radical-scavenging property and promoted cellular behaviors under hyperglycemia

The impairment of regenerative processes induced by high blood-glucose level (hyperglycemia) and excessive reactive oxygen species (ROS) contributes to the diabetic complication progression and development. In this study, an injectable, in situ crosslinkable chitosan hydrogel with ROS-scavenging capability was developed by conjugating gallic acid onto the chitosan backbone (CGA). We hypothesized that gallic acid serves as both antioxidant and crosslinking moieties to form hydrogel in situ by means of enzymatic crosslinking with horseradish peroxidase (HRP). The rapid gelation (from 30 s) was observed by vial tilting. The mechanical properties and microstructures of CGA hydrogels can be well controlled by varying the concentrations of H2O2. The ROS-scavenging ability of these CGA hydrogels was demonstrated against DPPH radical, hydroxyl radical, and total reducing power. Notably, in an in vitro hyperglycemia environment, CGA hydrogels significantly improved the proliferation and migration of human dermal fibroblast cells, which are closely related to diabetic wound healing. These results suggest that CGA hydrogels have potential as advanced materials for the treatment of diabetes-related diseases via attenuating the excessive ROS production and improving cellular behaviors.