Vascular endothelial growth factor a modified mRNA engineered cellular electrospun membrane complexes promotes mouse skin wound repair

Abstract

Artificial skin substitutes are one of the most promising areas of wound healing research; however, graft survival largely depends on how the treatment is performed. Early angiogenesis is essential for wound healing and graft survival and vascular endothelial growth factor A (VEGFA) is an important cytokine that stimulates angiogenesis. Here, we first investigated the effects of different ratios of collagen (BC) and gelatin blended with poly (l-lactide-co-caprolactone) (PLCL) on nanofibrous membranes. The Young's modulus and cell proliferation were significantly higher in the 50% BC group than that in all other groups. Then, cellular electrospun membrane complexes (CEMC) were successfully constructed from nanoscaffolds and fibroblasts extracted from human foreskin and engineered with controlled autocrine VEGFA by transfecting VEGFA modified mRNA (modRNA). Engineered CEMC significantly promoted wound healing in vivo and contributed to stable vascular network formation in the grafted area, thereby increasing the survival rate of the engineered skin. This study provides a potential solution for wound healing while establishing the value of different RNA modification methods for various engineered skins in the future, thereby advancing engineered skin development.

Keywords

• Cellular electrospun membrane complexes
• VEGFA
• Modified mRNA
• Tissue-engineered skin
• Wound healing