Injectable Immune-Regulating Mesenchymal Stem Cells Hydrogel for Localized Scleroderma Treatment

Bioactive hydrogels with anti-inflammatory, antioxidant, and pro-angiogenic properties are crucial for unlocking the full potential of mesenchymal stem cells (MSCs) therapy for scleroderma treatment. Here, drawing inspiration from the adhesion, antioxidant, and inflammation regulation ability of green tea, we introduce an injectable MSCs hydrogel containing immune-regulating polyphenol nanozymes to treat localized scleroderma. The hydrogel is constructed based on the dynamic Schiff reaction, which could endow it with injectability, self-healing function, and tissue adhesion. The introduction of natural polyphenol-based nanozymes can enhance the reactive oxygen species (ROS) scavenging and anti-inflammatory capabilities of the hydrogel and facilitate macrophage transformation. Besides, the hydrogel provides a conducive three-dimensional (3D) growth environment for MSCs <i>in vitro</i>, effectively promoting the ability of MSCs in the antifibrosis, vascular endothelial cells migration, and neovascularization. We have demonstrated that our hydrogel could accelerate the recovery of scleroderma lesions by inhibiting the expression of pro-inflammatory and fibrotic factors, promoting angiogenesis, remodeling skin appendages, and enhancing the expression of anti-inflammatory factors in a mouse scleroderma model. These results suggest that our injectable polyphenol nanozyme MSCs hydrogel presents a potential therapeutic strategy for managing scleroderma.