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.

Polycaprolactone (PCL) is a polymer material suitable for being prepared into porous scaffolds used in bone tissue engineering, however, insufficient osteogenic ability and mechanical strength limit its application. Zinc (Zn) alloy with proper mechanical strength and osteogenesis is a promising biodegradable metal that have attracted much attention. Herein, we combined the advantages of PCL and Zn by fabricating PCL/Zn composite scaffolds with different Zn powder contents (1 ​wt%, 2 ​wt%, 3 ​wt%) through fused deposition modelling. The ​mechanical property, cytocompatibility and Zn ​ions release ​behavior of PCL/Zn scaffolds were analyzed ​in vitro. The osteogenesis and osteoclastogenesis properties of the scaffolds were evaluated by being implanted into Sprague–Dawley rats calvaria defect. Results showed that the PCL/Zn scaffolds exhibited improved mechanical properties and cytocompatibility compared with the pure PCL scaffolds. At 8 weeks after in vivo implantaion, the addition of Zn powder promoted new bone formation, in a dose-dependent manner. The scaffolds with 2 ​wt% Zn displayed the best osteogenic effect, while the osteogenic effect was slightly reduced in the scaffolds with 3 ​wt% Zn. In the studied Zn contents, the PCL/Zn scaffolds gradually promoted osteoclastogenesis with increasd Zn content. In the 3 ​wt% Zn group, TRAP-positive cells were observed on the newly formed bone edges around the scaffolds. These dose-dependent effects were verified in vitro using MC3T3-E1 and RAW264.7 ​cells. Finally, we revealed that Zn²⁺ regulated osteogenesis and osteoclastogenesis by activation of the Wnt/β-catenin and NF-κB signalling pathways, respectively.