Skin injuries are frequently encountered in daily life, but deep wounds often poorly self-heal and do not recover completely. In this study, we propose a novel skin patch that combines antibiotic, cell-derived extracellular matrix (ECM) and biocompatible polyvinyl alcohol (PVA) hydrogel.

Methods: Decellularized human lung fibroblast-derived matrix (hFDM) was prepared on tissue culture plate (TCP) and PVA solution was then poured onto it. After a freeze-thaw process, PVA was peeled off from TCP along with hFDM tightly anchored to PVA. Subsequently, ciprofloxacin (Cipro)-incorporated PVA/hFDM (PVA/Cipro/hFDM) was fabricated via diffusion-based drug loading.

Results: In vitro analyses of PVA/Cipro/hFDM show little cytotoxicity of ciprofloxacin, stability of hFDM, rich fibronectin in hFDM, and good cell attachment, respectively. In addition, hFDM proved to be beneficial in promoting cell migration of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs) using transwell inserts. The antibacterial drug Cipro was very effective in suppressing colony growth of gram-negative and -positive bacteria as identified via an inhibition zone assay. For animal study, infected wound models in BALB/c mice were prepared and four test groups (control, PVA, PVA/Cipro, PVA/Cipro/hFDM) were administered separately and their effect on wound healing was examined for up to 21 days. The results support that Cipro successfully reduced bacterial infection and thus encouraged faster wound closure. Further analysis using histology and immunofluorescence revealed that the most advanced skin regeneration was achieved with PVA/Cipro/hFDM, as assessed via re-epithelialization, collagen texture and distribution in the epidermis, and skin adnexa (i.e., glands and hair follicles) regeneration in the dermis.

Conclusion: This work demonstrates that our skin patch successfully consolidates the regenerative potential of ECM and the antibacterial activity of Cipro for advanced wound healing.

Keywords: wound healing, skin patch, human fibroblast-derived matrix, ciprofloxacin, polyvinyl alcohol hydrogel

日常生活中经常会发生皮肤伤害，但深层伤口的自我修复能力通常很差，无法完全恢复。在这项研究中，我们提出了一种结合了抗生素，细胞衍生的细胞外基质（ECM）和生物相容性聚乙烯醇（PVA）水凝胶的新型皮肤贴剂。

方法：在组织培养板（TCP）上制备脱细胞的人肺成纤维细胞衍生基质（hFDM），然后倒入PVA溶液。冻融过程后，将PVA与hFDM紧密固定在PVA上，从TCP上剥离下来。随后，通过基于扩散的药物负载制备了环丙沙星（Cipro）并入的PVA / hFDM（PVA / Cipro / hFDM）。

结果：PVA / Cipro / hFDM的体外分析分别显示环丙沙星的细胞毒性，hFDM的稳定性，hFDM中富纤连蛋白和良好的细胞附着性。此外，hFDM被证明在使用Transwell插入物促进皮肤成纤维细胞和人脐静脉内皮细胞（HUVEC）的细胞迁移方面是有益的。抗菌药物Cipro在抑制革兰氏阴性菌和阳性菌的菌落生长方面非常有效，这是通过抑制区分析确定的。为了进行动物研究，制备了BALB / c小鼠的感染伤口模型，并分别给予了四个测试组（对照组，PVA，PVA / Cipro，PVA / Cipro / hFDM），并检查了它们对伤口愈合的影响长达21天。结果支持Cipro成功减少细菌感染，从而促进伤口更快闭合。

结论：这项工作表明我们的皮肤贴剂成功地巩固了ECM的再生潜力和Cipro对晚期伤口愈合的抗菌活性。

关键词：伤口愈合皮肤斑贴人成纤维细胞基质环丙沙星聚乙烯醇水凝胶