Prevascularized cell sheets enhance therapeutic effect of extracellular matrix scaffolds in a one-stage skin grafting rat model

Abstract

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

Keywords

Angiogenesis / Decellularized extracellular matrix / Dermal substitutes / Prevascularized human mesenchymal stem cell sheets / Skin grafts

Funding

This study was supported by the Natural Science Foundation of Guangdong Province (2020A1515110694).

Conflict of interest

The authors declare they have no competing interests.

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