In situ photocrosslinking ROS-adaptive caffeoyl chitosan/boronic acid-grafted gelatin hydrogels for treatment of combined radiation-burn injury.

Combined radiation-burn injury (CRBI) is a serious wound that is difficult to treat and typically results from radiation therapy, nuclear explosions, or nuclear accidents, where ionizing radiation and thermal burns usually occur simultaneously or sequentially. Excessive expression of reactive oxygen species (ROS) contributes to CRBI. Caffeic acid (CA) is a common natural antioxidant polyphenol whose clinical application is limited by its poor solubility and low stability. Here, we develop an in situ photocrosslinking caffeoyl chitosan/boronic acid-grafted gelatin hydrogel to treat CRBI. Caffeoyl chitosan (CCS) and boronic acid-grafted gelatin methacrylate (BGM) were synthesized. A CCS/BGM hydrogel was locally formed at the CRBI site due to the formation of dynamic caffeoyl/borate bonds and methacrylate photocrosslinking. The hydrogel showed appropriate swelling rates, mechanical properties, biosafety, and bioadhesion. ROS self-adaptive clearance of the hydrogel was realized by exposing CA phenolic groups after ROS breaking of caffeoyl/borate bonds to remove ROS. The hydrogel showed high mouse CRBI treatment efficacy by alleviating macrophages and proinflammatory cytokines (TNF-α and IL-6) and enhancing the expression of CD31 (a blood vessel formation biomarker). This ROS self-adaptive clearance hydrogel is a promising topical medicine for the treatment of high ROS-expressing CRBI and other complicated wounds.