Prevascularized cell sheets enhanced the therapeutic effect of ECM scaffolds in a one-stage skin grafting rat model

Dermal substitutes (DS) have been widely used in wound repair, but the survival rate of skin grafts with a DS remains an important challenge in regenerative medicine. In this study, we used porcine dermis-derived decellularized extracellular matrix (dECM) to construct an optimized 3D-printed DS, which exhibited the desired structure, good mechanical properties, and biocompatibility. Meanwhile, we constructed prevascularized human mesenchymal stem cell sheets (PHCS) with a certain microstructure, which could enhance microvessel formation and maturation and upregulate the expression of angiogenic growth factors. An immune competent one-stage skin graft model in vivo demonstrated that the P-DS group (PHCS + DS + STSG) could improve the repair effect of skin grafts, reduce graft fibrosis and later scar formation, increase the blood perfusion of skin grafts, through the early angiogenesis and the rapid microvessel maturation.  This study aims to investigate the efficacy of combining PHCS with DS in improving full-thickness wound healing.