Modular micro-vascular hydrogels with MSCs loading for localized scleroderma treatment

Abstract

Localized scleroderma (LoS) is an autoimmune connective tissue disease affecting the skin and internal organs, and current medications cannot cure it. Mesenchymal stem cells (MSCs) show great promise in treating autoimmune diseases, but the successful integration of MSCs with host tissues remains a challenge due to the absence of a functional vascular system. Here, we propose a novel injectable modular micro-vascular MSCs hydrogel (MVM-Gel) for localized scleroderma treatment. The modular endothelialized microvessels were constructed using a microfluidic technology combined with selective photopolymerization. The MSCs hydrogels were achieved by simply dispersing the generated microvessels into MSCs loaded fibrinogen solution. We have demonstrated that the MVM-Gel were with good injectable properties. Besides, these encapsulated MSCs could promote endothelial cell migration and expansion and secrete relevant factors to inhibit inflammation and promote repair. Thus, transplantation of MVM-Gel can significantly reduce inflammation, alleviate collagen deposition, promote vascular tissue formation, and inhibit fibrosis and peripheral inflammation in LoS mice. We believe that our injectable MVM-Gel will provide a potential option for the clinical treatment of topical scleroderma.