Abstract
Diabetes is one of the most prevalent chronic metabolic diseases worldwide, and its incidence continues to rise. Diabetes-related complications have become a major public health concern, with diabetic chronic wounds—particularly diabetic foot ulcers—representing one of the most challenging and clinically significant manifestations. These non-healing wounds often require prolonged recovery, severely impair patients’ quality of life, and impose substantial economic and psychological burdens on healthcare systems and families. Conventional therapeutic approaches are limited by insufficient reparative capacity, scarcity of functional tissue sources, and the inability to achieve durable structural and functional restoration, frequently resulting in suboptimal outcomes. Recent advances in stem cell engineering and three-dimensional tissue technologies have enabled the development of organoids—emerging biomimetic regenerative constructs—allowing their increasing application in tissue repair, including diabetic ulcers. This review provides an integrated summary of the major barriers to diabetic wound healing, the regenerative mechanisms of skin organoids, and recent progress in this field. Unlike previous reviews that address organoids or wound healing separately, this work specifically focuses on diabetic chronic wounds while emphasizing engineering strategies, regenerative potential, and translational considerations. We further analyze the key challenges that hinder clinical translation, including model consistency, vascularization capacity, long-term functional stability, immune compatibility, potential tumorigenicity, and interactions with the local microenvironment. Collectively, this work aims to provide a structured framework and future research directions for the application of skin organoids in diabetic chronic wound repair, supporting their responsible transition from experimental research toward clinical practice.