Sustained release of magnesium and zinc ions synergistically accelerates wound healing

Fan Yang; Yijia Xue; Feilong Wang; Danni Guo; Yunjiao He; Xiao Zhao; Fanyu Yan; Yuqian Xu; Dandan Xia; Yunsong Liu

doi:10.1016/j.bioactmat.2023.02.019

Sustained release of magnesium and zinc ions synergistically accelerates wound healing

Bioact Mater. 2023 Feb 24:26:88-101. doi: 10.1016/j.bioactmat.2023.02.019. eCollection 2023 Aug.

Authors

Fan Yang^{1

2}, Yijia Xue^{1

2}, Feilong Wang^{1

2}, Danni Guo^{1

2}, Yunjiao He^{1

2}, Xiao Zhao^{1

2}, Fanyu Yan^{1

2}, Yuqian Xu^{1

2}, Dandan Xia^{2

3}, Yunsong Liu^{1

2}

Affiliations

¹ Department of Prosthodontics, Peking University Hospital of Stomatology, Beijing, 100081, China.
² National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing, 100081, China.
³ Department of Dental Materials, Peking University Hospital of Stomatology, Beijing, 100081, China.

Abstract

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.

Keywords: Biodegradable magnesium; Biodegradable zinc; GelMA hydrogel; STAT3 signaling pathway; Skin wound healing.