Engineering bioactive materials for diabetic wound healing

Diabetic wound healing is entangled in a dysregulated cascade of interconnected pathologies, where persistent hyperglycemia fuels a vicious cycle of oxidative stress, chronic inflammation, compromised angiogenesis, and heightened infection risk. Traditional unimodal therapies often fail to address this multifaceted pathophysiology, necessitating the development of advanced bioactive materials that can actively orchestrate the repair process. This review systematically outlines the paradigm shift from passive wound dressings to rationally engineered therapeutic systems. We discuss the design and application of a new generation of bioactive materials, encompassing antioxidant/anti-ferroptotic therapies, anti-inflammatory/pyroptotic modulators, plant-derived composites, cell- and extracellular vesicle-based biomaterials, and formulations incorporating cytokines, trace elements, hypoglycemic agents, or antimicrobials. These smart systems, often featuring stimuli-responsive, controlled-release, and multifunctional properties, can dynamically correct multiple pathological imbalances simultaneously. They serve as active therapeutic platforms, moving beyond static protection to dynamically regulate the pathological wound milieu by scavenging reactive oxygen species, reprogramming macrophage polarization, promoting angiogenesis, and combating infection. In addition, this review critically examines the current landscape of clinical translation, highlighting the challenges and evidence gaps. In conclusion, the ongoing development of these rationally designed therapeutic modalities holds strong promise for translating advanced material science into clinically effective therapies, with the ultimate goal of improving healing outcomes and quality of life for diabetic patients.