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. 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). 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. 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 application.

中文翻译：

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单阶段移植联合表皮干细胞通过诱导早期血管生成促进组织工程皮肤的存活

分层厚度皮肤移植物 (STSG) 与脱细胞真皮基质 (ADM) 的复合移植是一种很有前途的全层皮肤缺损修复方法。由于 ADM 的延迟血管形成，目前没有可用的工程皮肤组织能够通过单阶段程序永久覆盖全层皮肤缺损。已发现表皮干细胞 (EpSC) 可促进伤口床中的血管生成。EpSCs是否能诱导真皮替代物的早期血管生成，促进单期组织工程皮肤移植的成活还有待进一步研究。在体外，用在 ADM 中培养的 EpSC 上清液处理大鼠血管内皮细胞 (RVEC) 并刺激 48 小时。通过 RNA 测序和管形成测定分析 RVEC。对于体内实验，75 只大鼠随机分为五组：ADM、ADM + EpSCs (AE)、STSG、ADM + STSG (AS) 和 ADM + STSG + EpSCs (ASE) 组。通过一般观察和 H&E 和 Masson 染色评估伤口愈合的质量。使用LDPI系统评估血液灌注量，并通过免疫组织化学（IHC）测定血管标志物的表达。如管形成实验和 RNA-seq 所示，在 ADM 中培养的 EpSC 分泌的活性物质促进了血管生成。EpSCs 促进 ADM 的上皮化和 ADM 植入物的血管化。与 AS 组和 STSG 对照组相比，ASE 组皮肤移植物存活率显着增加，皮肤收缩减少，美容外观改善。总之，