Decellularized extracellular matrix (ECM)-based scaffold has been a very useful resource for effective tissue regeneration. In this study, we report a novel ECM patch that physically combines human fibroblast-derived matrix (hFDM) and poly(vinyl alcohol) (PVA) hydrogel. hFDM was obtained after decellularization of in vitro cultured human fibroblasts. We investigated the basic characteristics of hFDM alone using immunofluorescence (fibronectin, collagen type I) and angiogenesis-related factor analysis. Successful incorporation of hFDM with PVA produced an hFDM/PVA patch, which showed excellent cytocompatibility with human mesenchymal stem cells (hMSCs), as assessed via cell adhesion, viability, and proliferation. Moreover, in vitro scratch assay using human dermal fibroblasts showed a significant improvement of cell migration when treated with the paracrine factors originated from the hMSC-incorporated hFDM. To evaluate the therapeutic effect on wound healing, hMSCs were seeded on the hFDM/PVA patch and they were then transplanted into a mouse full-thickness wound model. Among four experimental groups (control, PVA, hFDM/PVA, hMSC/hFDM/PVA), we found that hMSC/hFDM/PVA patch accelerated the wound closure with time. More notably, histology and immunofluorescence demonstrated that compared to the other interventions tested, hMSC/hFDM/PVA patch could lead to significantly advanced tissue regeneration, as confirmed via nearly normal epidermis thickness, skin adnexa regeneration (hair follicle), mature collagen deposition, and neovascularization. Additionally, cell tracking of prelabeled hMSCs suggests the in vivo retention of transplanted cells in the wound region after the transplantation of hMSC/hFDM/PVA patch. Taken together, our engineered ECM patch supports a strong regenerative potential toward advanced wound healing.

中文翻译：

---

新型ECM修补程序结合了聚乙烯醇，人类成纤维细胞衍生基质和间充质干细胞进行高级伤口愈合

基于脱细胞的细胞外基质（ECM）的支架已成为有效组织再生的非常有用的资源。在这项研究中，我们报告了一种新型的ECM贴片，该贴片在物理上结合了人类成纤维细胞衍生的基质（hFDM）和聚乙烯醇（PVA）水凝胶。在体外培养的人成纤维细胞脱细胞后获得hFDM 。我们使用免疫荧光（纤连蛋白，I型胶原）和血管生成相关因子分析研究了单独的hFDM的基本特征。hFDM与PVA的成功结合产生了hFDM / PVA贴片，通过细胞粘附，生存能力和增殖评估，该贴片与人间充质干细胞（hMSCs）具有出色的细胞相容性。而且，体外使用源自人类hMSC的hFDM的旁分泌因子治疗时，使用人类皮肤成纤维细胞的刮擦试验显示细胞迁移有显着改善。为了评估对伤口愈合的治疗效果，将hMSC接种在hFDM / PVA贴片上，然后将其移植到小鼠全厚度伤口模型中。在四个实验组（对照组，PVA，hFDM / PVA，hMSC / hFDM / PVA）中，我们发现hMSC / hFDM / PVA贴剂随着时间的推移加速了伤口闭合。更值得注意的是，组织学和免疫荧光显示，与其他测试干预相比，hMSC / hFDM / PVA贴片可导致明显的组织再生，这通过近乎正常的表皮厚度，皮肤附件再生（毛囊），成熟的胶原沉积和新血管形成。另外，hMSC / hFDM / PVA贴片移植后，移植细胞在伤口区域的体内保留率。综上所述，我们精心设计的ECM贴片可为晚期伤口愈合提供强大的再生潜力。