ROS-responsive drug delivery systems for chronic wound healing: advances, challenges, and translational perspectives

Chronic wounds pose a substantial global health burden, due to the high incidence and recurrence rates, and associated morbidity. Excessive and sustained production of reactive oxygen species (ROS) is a hallmark of the chronic wound microenvironment, ultimately stalling the repair process. The pathological accumulation of ROS in chronic wounds has motivated the development of ROS-responsive drug delivery systems (DDS), which show considerable potential in improving wound healing outcomes. In this review, we provide a comprehensive overview of the advances in ROS-responsive DDS for chronic wound healing, summarizing the design principles, material chemistry, and underlying ROS-triggered functional mechanisms. Key translational challenges are discussed, including material biocompatibility, stability in protease- and ROS-rich wound exudates, manufacturing scalability, and regulatory considerations. Finally, we outline future perspectives, emphasizing the integration of multi-responsive functionalities, real-time ROS monitoring, and advanced biomaterial engineering to accelerate clinical translation. By aligning therapeutic release with the dynamic redox status of chronic wounds, ROS-responsive DDS holds considerable potential to redefine precision therapy for wound management.