Metal ion formulations for diabetic wound healing: Mechanisms and therapeutic potential

Metals are vital in human physiology, which not only act as enzyme catalysts in the processes of superoxide dismutase and glucose phosphorylation, but also affect the redox process, osmotic adjustment, metabolism and neural signals. However, metal imbalances can lead to diseases such as diabetes, which is marked by chronic hyperglycemia and affects wound healing. The hyperglycemic milieu of diabetes impairs wound healing, posing significant challenges to patient quality of life. Wound healing encompasses a complex cascade of hemostasis, inflammation, proliferation, and remodeling phases, which are susceptible to disruption in hyperglycemic conditions. In recent decades, metals have emerged as critical facilitators of wound repair by enhancing antimicrobial properties (e.g., iron and silver), providing angiogenic stimulation (copper), promoting antioxidant activity and growth factor synthesis (zinc), and supporting wound closure (calcium and magnesium). Consequently, research has pivoted towards the development of metal ion-based therapeutics, including innovative formulations such as nano-hydrogels, nano-microneedle dressings, and microneedle patches. Prepared by combining macromolecular materials such as chitosan, hyaluronic acid and sodium alginate with metals, aiming at improving the management of diabetic wounds. This review delineates the roles of key metals in human physiology and evaluates the application of metal ions in diabetic wound management strategies.