Advanced Responsive Hydrogels for Diabetic Wound Healing: Design Principles, Controlled Drug Delivery, Therapeutic Strategies, and Application Prospects

Diabetic wounds characterized by impaired healing and amputation risks, pose clinical challenge worldwide. Hydrogel dressings have emerged as a promising therapeutic strategy due to their ability to absorb exudate, prevent infections, and control therapeutic agents delivery, with over a dozen products clinically approved or in trials. However, these hydrogels rely on passive drug release mechanisms, which do not dynamically respond to the pathological microenvironment of diabetic wounds, such as high glucose, elevated ROS, acidic pH, and increased enzyme activity, resulting in mismatched release kinetics and suboptimal therapeutic outcomes. To address these challenges, researchers have developed smart responsive hydrogels that utilize the wound's endogenous pathological cues as triggers for on-demand, spatiotemporal drug delivery. This approach enables personalized therapy by precisely modulating drug release in response to real-time wound changes, offering a transformative solution for enhancing healing efficacy. Herein, we review the pathological features of diabetic wounds, and then explores the design principles and therapeutic strategies of smart responsive hydrogels. Importantly, the review evaluates the challenges associated with these technologies and outlines future engineering directions to optimize their clinical adoption. This review aims to contribute to the rational design and practical clinical application of smart hydrogels for chronic wound care.