Effects of reactive oxygen species and antioxidant strategies on wound healing in diabetes

With the rising global prevalence of diabetes, the rate of chronic wounds associated with this disease is also escalating. Although the mechanisms underlying this trend are not fully understood, accumulating evidence suggests a critical role for reactive oxygen species (ROS). Increased blood glucose levels, bacterial infections, and impaired energy utilization lead to an imbalance between oxidative and antioxidant responses, resulting in ROS accumulation. The cellular antioxidant system can manage a small amount of ROS; however, excessive exogenous ROS acts upon the cell membrane or even penetrates the cell, consequently affecting its activity. Excessive ROS cause enhanced expression of inflammatory factors, impaired cellular proliferation, vascular vessel damage, and extracellular matrix remodeling disturbance, ultimately hindering diabetic wound healing. The regulation of ROS during wound healing is intricate and involves diverse mechanisms throughout the entire wound-healing process. This review provides a systematic overview of the relationship between ROS and inflammatory signaling pathways in diabetic wounds along with the most recent antioxidant strategies targeting these pathways. The aim of this review was to outline effective strategies for mitigating oxidative stress in chronic wounds and to provide novel insights into future research.