Injectable Multifunctional Hyaluronan based Hydrogel Suppressing the Excessive Glucose and Reactive Oxygen Species in Diabetic Wound Treatment

Abstract

In diabetic wounds, the overlapping presence of excessive glucose and reactive oxygen species (ROS) forming a vicious cycle that severely impedes the wound healing process. Despite advancements in wound care, current treatments often limit in addressing these two critical factors simultaneously. To address these challenges, this study introduces a multifunctional hydrogel system capable of dual regulation of excessive glucose and ROS levels in a hyperglycemic environment, while also provide a platform with favorable properties that support wound healing. First, by modifying hyaluronic acid (HA) chains with vinyl sulfone and thiol functional groups, the resulting hydrogel exhibited tunable gelation time, elastic modulus, and degradation rates, making it adaptable for diabetic wound management. Notably, this hydrogel allows for precise glucose and ROS regulation by encapsulating glucose oxidase (GOx), horseradish peroxidase (HRP), and tannic acid (TA) within the HA hydrogel matrix. It was verified that the hydrogels could reduce the glucose levels to desired concentration by varying the encapsulated GOx content. Simultaneously, the combined ROS-scavenging effect of HRP and TA effectively addressed the excessive ROS problem. Specifically, H2O2 generated from the GOx-glucose reaction was consumed in the HRP-mediated polymerization of TA, and free radicals (OH•, DPPH) were scavenged up to 70% by TA. Due to the glucose and ROS regulation properties, this hydrogel system was able to promote the proliferation and migration of human dermal fibroblast in a hyperglycemic environment. Overall, this study offers a simple and effective approach to regulate the excessive levels of glucose and ROS in a hyperglycemic condition, which has potential in creating a multifunctional platform for diabetic wound treatment.