The Trilogy of Skin Regeneration via Metal-Organic Frameworks Nanomedicine: Precision Management of Refractory Wounds, Pathological Scarring, and Hair Follicle Reactivation.

Diabetic infected wounds represent a formidable clinical challenge characterized by persistent hyperglycemia-induced pathological cascades that disrupt normal healing processes through multiple mechanisms including chronic inflammation, oxidative stress, and microvascular dysfunction. As prototypical chronic wounds, they exhibit severely impaired tissue regeneration due to this multifaceted dysfunction in both skin architecture and biological function. Metal-organic frameworks (MOFs) have emerged as promising next-generation therapeutic platforms owing to their exceptional structural tunability, multifunctional properties, and precise spatiotemporal drug delivery capabilities. This review examines several critical aspects: (1) fundamental MOF classifications and advanced synthesis methodologies; (2) metal-specific (Zn²⁺, Cu²⁺, Ag⁺, etc.) therapeutic mechanisms against diabetic wound infections; (3) extended applications in pathological scar modulation and hair follicle regeneration through targeted molecular pathway regulation; and (4) the integrated "healing-scar suppression-functional restoration" treatment paradigm. We further elucidate critical unresolved challenges in MOF-based skin regeneration, including long-term biosafety and large-scale production issues while providing a comprehensive theoretical framework for future translational research. By uniting prior MOF studies on scar and hair regeneration with pro-healing paradigms, this discussion frames design principles for concurrent structural and functional repair, guiding MOF research from healing to regeneration.