The integration of biomaterials with cells for high overall performances is vitally important in tissue engineering, as scaffold-free cell sheet lacks enough mechanical performance and cell viability while cell-free scaffold possesses limited biological functions. In this study, we propose a new strategy to strengthen cell sheets and enhance cell activity for accelerating wound healing based on a novel sandwich structure of cell sheet-plasmid@membrane-cell sheet (CpMC). Specifically, the CpMC contains two adipose-derived stem cell (ADSC) sheets on outer surfaces and an electrospun gelatin/chitosan nanofibrous membrane (NFM) encapsulating vascular endothelial growth factor (VEGF) plasmids in between. The physicochemical properties of NFM including swelling, stiffness, strength, elasticity, and biodegradation can be tailored by simply adjusting the ratio between gelatin and chitosan to be 7:3 which is optimal for most effectively supporting ADSCs adhesion and proliferation. The swelling/biodegradation of NFM mediates the sustained release of encapsulated VEGF plasmids into adjacent ADSCs, and NFM assists VEGF plasmids to promote the differentiation of ADSCs into endothelial, epidermal, and fibroblast cells, in support of the neoangiogenesis and regeneration of cutaneous tissues within 2 weeks. The proposed membrane-supporting cell sheet strategy provides a new route to tissue engineering, and the developed CpMC demonstrates a high potential for clinical translation.

中文翻译：

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新型纳米纤维膜支持干细胞片，用于质粒递送和细胞激活，以加速伤口愈合


将生物材料与细胞整合以获得高整体性能在组织工程中至关重要，因为无细胞支架的细胞片缺乏足够的机械性能和细胞活力，而无细胞支架的生物学功能有限。在这项研究中，我们提出了一种基于细胞片-质粒@膜-细胞片（CpMC）的新型三明治结构来强化细胞片并增强细胞活性以加速伤口愈合的新策略。具体来说，CpMC 的外表面包含两个脂肪源性干细胞 (ADSC) 片，其间包含包裹血管内皮生长因子 (VEGF) 质粒的电纺明胶/壳聚糖纳米纤维膜 (NFM)。 NFM 的理化特性包括膨胀、刚度、强度、弹性和生物降解，只需将明胶和壳聚糖之间的比例调整为 7:3，这是最有效支持 ADSC 粘附和增殖的最佳选择。 NFM的肿胀/生物降解介导封装的VEGF质粒持续释放到邻近的ADSC中，并且NFM协助VEGF质粒促进ADSC分化为内皮细胞、表皮细胞和成纤维细胞，支持2年内皮肤组织的新生血管生成和再生。几周。所提出的膜支持细胞片策略为组织工程提供了一条新途径，开发的 CpMC 展示了临床转化的巨大潜力。