Innovative Approaches to Diabetic Wound Healing: Focusing on ROS and Redox Signals

Reactive oxygen species (ROS) play a critical role in the pathophysiology of diabetic wound healing. In the early stages, a moderate increase in ROS levels is beneficial, as it enhances phagocytic activity and provides defense against external damage. However, as healing progresses, excessive ROS production induces oxidative stress, reduces antioxidant enzyme activity, and leads to redox imbalance─ultimately contributing to the development of chronic diabetic wounds. This review comprehensively explores the role of ROS across various phases of the wound-healing process and elucidates the associated signaling pathways. It also examines the influence of ROS on key mediators of wound healing, including macrophages and matrix metalloproteinases. To modulate ROS levels and promote efficient wound healing, we discuss a range of antioxidant-based therapeutic strategies, such as the application of biopolymers and antioxidant enzymes. Among the diverse antioxidant strategies, nanozymes stand out for their inherent ability to mimic the catalytic functions of natural enzymes. Owing to their unique ROS scavenging capabilities, they hold great promise in addressing the key challenges associated with anti-ROS therapy. Nanozymes provide several distinct advantages, including enhanced stability, multifunctionality, and tunable catalytic activity. Moreover, they play a crucial role in modulating the inflammatory responses induced by the pathological microenvironment. The article further highlights the potential of phytoconstituents in mitigating oxidative stress and restoring redox balance. Additionally, it addresses current treatment strategies for diabetic wound management, while also evaluating the clinical progress and challenges associated with their development.