Sustained release of magnesium and zinc ions synergistically accelerates wound healing

Skin wounds are a major medical challenge that threaten human health. Functional hydrogel dressings demonstrate great potential to promote wound healing. In this study, magnesium (Mg) and zinc (Zn) are introduced into methacrylate gelatin (GelMA) hydrogel via low-temperature magnetic stirring and photocuring, and their effects on skin wounds and the underlying mechanisms are investigated. Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions (Mg²⁺) and zinc ions (Zn²⁺) in a sustained manner. The Mg²⁺ and Zn²⁺ not only enhanced the migration of human skin fibroblasts (HSFs) and human immortalized keratinocytes (HaCats), but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix. Moreover, the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition, angiogenesis and skin wound re-epithelialization. We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing: the Mg²⁺ promoted Zn²⁺ entry into HSFs and increased the concentration of Zn²⁺ in HSFs, which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway. The synergistic effect of Mg²⁺ and Zn²⁺ promoted wound healing. In conclusion, our study provides a promising strategy for skin wounds regeneration.