Exosome/sEV therapy for diabetic wounds: Promise and evidence gaps in re-epithelialization

Diabetic skin wounds, especially diabetic foot ulcers, are common and hard to heal. Rebuilding the epidermal barrier depends on keratinocytes at the wound edge, which must activate, migrate, proliferate, redifferentiate, and restore cell junctions and barrier structures. The review points out that this process is more accurately described by epithelial–mesenchymal plasticity (EMP) than by a binary EMT-based model, as the phenotypic changes are transient, reversible, and stage-dependent. In diabetic wounds, high glucose and other pathological factors disrupt this process. Exosomes/sEVs may support re-epithelialization by directly acting on keratinocyte repair programs, or indirectly remodeling the inflammatory, vascular, oxidative, and extracellular matrix (ECM) microenvironments.

However, most studies use wound closure, histological re-epithelialization, angiogenesis, inflammation, or collagen deposition as endpoints. Direct evidence linking exosome/sEV treatment to coordinated EMP-associated state transitions, epithelial redifferentiation, and barrier recovery in diabetic wound keratinocytes remains limited. The authors propose four evidence levels: direct EMP evidence, functional keratinocyte evidence, indirect microenvironmental support, and mechanistic inference. They also discuss engineered vesicles, local delivery systems, evidence maturity, and translational risks.

The work titled “Exosome-Mediated Regulation of Re-Epithelialization and Epithelial–Mesenchymal Plasticity in Diabetic Cutaneous Wounds: Current Advances and Translational Perspectives” was published on Skin (published on September 3, 2026).