Zhiyong Wang1†, Hailin Xu1†, Hao Yang1†, Yi Zhang3 , Xiaoyan Wang1 , Peng Wang1 , Zhongye Xu1 ,Dongming Lv1 , Yanchao Rong1 , Yunxian Dong4 , Bing Tang1 , Zhicheng Hu1*, Wuguo Deng2* and Jiayuan Zhu1*

Abstract

Background The composite transplantation of a split-thickness skin graft (STSG) combined with an acellular dermal matrix (ADM) is a promising repair method for full-thickness skin defects. Due to delayed vascularization of the ADM, no currently available engineered skin tissue is able to permanently cover full-thickness skin defects via a single-stage procedure. Epidermal stem cells (EpSCs) have been found to promote angiogenesis in the wound bed. Whether EpSCs can induce early angiogenesis of dermal substitutes and promote the survival of single-stage tissue-engineered skin transplantation needs to be further studied.

Methods In vitro, rat vascular endothelial cells (RVECs) were treated with the supernatant of EpSCs cultured in ADM and stimulated for 48 h. RVECs were analysed by RNA sequencing and tube formation assays. For the in vivo experiment, 75 rats were randomly divided into five groups: ADM, ADM+EpSCs (AE), STSG, ADM+STSG (AS), and ADM+STSG+EpSCs (ASE) groups. The quality of wound healing was estimated by general observation and H&E and Masson staining. The blood perfusion volume was evaluated using the LDPI system, and the expression of vascular markers was determined by immunohistochemistry (IHC).

Results The active substances secreted by EpSCs cultured in ADM promoted angiogenesis, as shown by tube formation experiments and RNA-seq. EpSCs promoted epithelialization of the ADM and vascularization of the ADM implant. The ASE group showed significantly increased skin graft survival, reduced skin contraction, and an improved cosmetic appearance compared with the AS group and the STSG control group.

† Zhiyong Wang, Hailin Xu and Hao Yang contributed equally to this work

*Correspondence:

Zhicheng Hu 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

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Conclusions In summary, our findings suggest that EpSCs promote the formation of new blood vessels in dermal substitutes and support one-step transplantation of tissue-engineered skin, and thereby provide new ideas for clinical

Keywords Epidermal stem cells, Acellular dermal matrix, Tissue-engineered skin, Vascularization, Angiogenesis