Hydrogel‐Based ROS‐Regulating Strategy: Reprogramming the Oxidative Stress Imbalance in Advanced Diabetic Wound Repair

Due to hyperglycemia and redox imbalance, diabetic wounds are prone to recurrent ulceration and non-healing, severely affecting patients' quality of life. Excessive reactive oxygen species (ROS) in wounds impede repair by damaging proteins and nucleic acids, activating inflammation, and suppressing immunity. A growing body of evidence suggests that harnessing the high oxidative stress within the microenvironment and modulating ROS levels to overcome repair barriers has become a breakthrough in treating chronic diabetic wounds. Hydrogels, with excellent biocompatibility and designability, are key for intelligent ROS regulation. Here, the role of ROS in the progression of diabetic skin wounds is detailed, which includes inducing oxidative damage, exacerbating inflammation and immune imbalance, as well as degrading the extracellular matrix (ECM), hindering neovascularization, and inhibiting nerve repair. Then, the ROS-regulating strategy based on the hydrogel platform is discussed. Engineered hydrogels adjust ROS levels via external stimulus such as light, ultrasound, and electricity, or the microenvironment of hyperglycemia, oxidative stress, and acidity in wounds, and even bidirectionally in specific spatiotemporal contexts. Furthermore, the therapeutic and repair potential of ROS-regulated hydrogels in the healing process of diabetic wounds is outlined, the current deficiencies in the field of diabetic wounds treatment are addressed, and prospects for the future are proposed.