Integrating Regenerative Therapies and Artificial Intelligence for Precision Management of Diabetic Foot Ulcers

SIGNIFICANCE: Diabetic foot ulcers (DFUs) represent one of the most devastating complications of diabetes, leading to high rates of amputation and mortality. Their multifactorial pathogenesis-including neuropathy, ischemia, infection, and immune dysfunction-creates a chronic inflammatory microenvironment that impairs tissue repair and regeneration. RECENT ADVANCES: Emerging regenerative strategies using stem cells and extracellular vesicles (EVs) have demonstrated potential to restore vascularization and modulate inflammation. In particular, miRNA-enriched EVs regulate key wound-healing pathways such as angiogenesis, extracellular matrix remodeling, and oxidative stress response. Meanwhile, small-molecule drugs targeting hypoxia and inflammatory cascades are being explored to enhance re-epithelialization and fibroblast migration. Parallel advances in artificial intelligence (AI) and optical sensing-using visible, infrared, or hyperspectral imaging-enable automated wound detection, tissue classification, and healing prediction with high accuracy. CRITICAL ISSUES: Despite these developments, translation remains limited by unstable therapeutic efficacy, variable biomarker expression, and the absence of standardized evaluation systems. AI-based wound assessment requires robust datasets and clinical validation to ensure reliability across diverse populations. FUTURE DIRECTIONS: Integrating molecular-targeted therapies with AI-assisted diagnostic platforms could establish a next-generation DFU management framework-combining precise molecular intervention, automated wound monitoring, and personalized treatment planning-to achieve reliable, real-time, and patient-centered wound care.