Ai Xuefeng, Luo Runjiao, Wang Huijing, Yan Bingqian, Li Kaixiang, Yu Xindi, Dong Wei, Tan Yao, Liu Minglu, Chen Ying, Lu Tingting, Wang Xiangying, Wang Wei, Fu Wei
Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Institute of Pediatric Translational Medicine, Shanghai Institute for Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, China.
Mater Today Bio. 2023 Aug 23;22:100776. doi: 10.1016/j.mtbio.2023.100776. eCollection 2023 Oct.
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--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 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.
人工皮肤替代品是伤口愈合研究中最具前景的领域之一;然而,移植成活率在很大程度上取决于治疗的实施方式。早期血管生成对于伤口愈合和移植成活至关重要,而血管内皮生长因子A(VEGFA)是一种刺激血管生成的重要细胞因子。在此,我们首先研究了胶原蛋白(BC)和明胶与聚(L-丙交酯-ε-己内酯)(PLCL)以不同比例混合对纳米纤维膜的影响。50% BC组的杨氏模量和细胞增殖显著高于所有其他组。然后,利用从人包皮中提取的纳米支架和成纤维细胞,通过转染VEGFA修饰mRNA(modRNA)构建可控自分泌VEGFA的细胞电纺膜复合物(CEMC)。工程化CEMC显著促进伤口愈合,并有助于在移植区域形成稳定的血管网络,从而提高工程皮肤的成活率。本研究为伤口愈合提供了一种潜在的解决方案,同时确立了未来不同RNA修饰方法对各种工程皮肤的价值,从而推动工程皮肤的发展。