Abstract
<jats:p>Significance: Chronic wounds are a growing public-health and economic burden. In the United States, about one-sixth of Medicare beneficiaries (~10.5 million people) carry a chronic wound, with Medicare spending an estimated $22.5 billion annually and global wound-care expenditure reached $148.65 billion in 2022. This review, written for clinicians and biomedical engineers, is organized from basic to advanced.Recent Advances: It defines normal skin architecture and regional variation, classifies the full spectrum of skin injury, and describes the body’s coupled tissue repair and immune response. It quantifies the epidemiology, risk, and mortality of the principal chronic wounds: arterial/ischemic, venous leg, and diabetic foot ulcers, pressure injury, and non-healing surgical wounds, and summarizes the clinical evidence and biological mechanisms of current chronic wound management strategies including revascularization, pressure redistribution, hyperbaric oxygen, debridement, infection control, and moisture-balancing, negative-pressure, growth factor, and skin substitute treatments, and it points to the databases, guidelines, and registries that anchor evidence-based practice.Critical Issues: The normal acute trajectory, which recovers only to about 70-80% of tensile strength, is contrasted with chronic wounds that stall in a self-sustaining inflammatory state marked by sustained neutrophils, cytokines, and M1 macrophages, bacterial biofilm, elevated matrix metalloproteinases, fibroblast senescence, and stalled keratinocytes, that recur or resist standard care despite management.Future Directions: Urgent unmet needs, from durable infection control to true regeneration and personalized care, are increasingly addressed through medical devices and engineered biomaterials.</jats:p>