Antioxidative bioactive glass reinforced injectable hydrogel with reactive oxygen species scavenging capacity for diabetic wounds treatment

Abstract

Diabetic wound healing remains a critical challenge due to its special hyperglycemic environment and disorder in wound healing process. The hyperglycemic microenvironment of diabetic wounds causes inhibitive angiogenesis and overproduction of reactive oxygen species (ROS), which leads to oxidative stress damage to biological macromolecules and cells, and hindrance of wound healing. Herein, an injectable thermo-sensitive methyl cellulose hydrogel with capacities of improving angiogenesis, scavenging ROS and antibiosis is developed to overcome the obstacles of diabetic wound healing. Through loading antioxidative cerium-doped bioactive glass nanoparticles (CeBG), the hydrogel demonstrates efficient ROS scavenging to protect cells from oxidative stress harm, as well as stimulation of dermal fibroblast proliferation and migration. Moreover, addition of quaternary chitosan (QCS) endows the hydrogel with antibacterial ability against E. coli and S. aureus. The hydrogel effectively accelerates diabetic wound healing in a mice model, and more importantly, the wound area presents improved angiogenesis, diminished inflammation and decreased ROS level. These data demonstrate that the hydrogel is a promising biomaterial for the clinical treatment of diabetic wounds, as well as facilitating the therapy of oxidative stress related diseases.