A Nanostructured Skin Patch to Heal Chronic Wounds

摘要 慢性无法愈合的伤口具有很高的发病率和死亡率，使人虚弱。它是广泛的和代价高昂的 治疗(例如，仅在美国就有大约150亿美元/年用于治疗静脉性腿部溃疡)。尽管做出了广泛的努力来 开发有效治疗慢性伤口的治疗策略，到目前为止，临床上取得的成功有限 已经实现了。目前可用的设备和产品仅针对一个或多个复杂设备而设计 慢性创面的细胞和分子功能受损。 治疗和治疗慢性皮肤越来越重要的临床意义和医疗和社会责任 伤口正在推动对高效设计和制造的伤口愈合设备的开发需求。 一种系统，它不仅具有皮肤的物理机械特性，而且还可以纠正或避免 慢性创面分子和细胞机制受损，包括血管生成、上皮迁移和 细胞增殖，未解决的炎症和感染，将是一个重大的进步。 拟议的研究项目旨在开发一种具有独特恢复能力的多功能贴片 身体治愈慢性伤口的能力。在这方面，我们开发了一种纳米挤压方法来制造 多功能纳米纤维复合贴片能够解决与 慢性伤口的愈合过程，包括i)提供适当的环境，使细胞容易 增殖并形成新的血管；ii)使用阿魏醇预防或减少现有的细菌感染 带有和不带有蛋白质电晕的纳米颗粒；以及iii)最大限度地减少不平衡和长期的炎症。我们 计划均匀整合多功能生物分子(例如，卵泡抑素样1、Ac2-26和 阿魏酸甘油酯纳米粒)，以加速血管生成和细胞增殖，而 将细菌感染和长期炎症的风险降至最低。广泛的体外和体内实验 将对新型贴片的治疗效果进行研究。对于体内实验，我们使用了一种大鼠模型 由Charles River提供的糖尿病贴片，以探索该贴片的治疗和抗菌效果。牵涉其中 细胞和免疫系统与多功能贴片相互作用的机制将通过 广泛的分析，包括先进的电子显微镜。 本研究将为新型组织工程支架材料的开发奠定基础 自然(内源性)修复机制通过重定向受损的修复途径，从而提供一种独特的 有机会修复和再生各种慢性伤口的受损皮肤和组织。

ABSTRACT Chronic nonhealing wounds are debilitating with high morbidity and mortality. It is widespread and costly to treat (e.g. ~ $15 billion/year for venous leg ulcers in the United States alone). Despite extensive efforts to develop therapeutic strategies for effective treatment of chronic wounds, so far, limited clinical success has been achieved. Currently available devices and products are designed only to target one or more complex impaired cellular and molecular functions in chronic wounds. The increasing clinical significance and medical and social responsibilities to treat and cure chronic skin wounds are driving the demand for development of efficiently designed and fabricated wound-healing devices. A system that not only possesses the physico-mechanical properties of skin, but also corrects or avoids the impaired molecular and cellular machinery of chronic wounds, including angiogenesis, epithelial migration and cell proliferation, unresolved inflammation, and infection, would be a major advance. The proposed research project is aimed to develop a multifunctional patch with a unique capacity to resume bodies' capacity to heal chronic wounds. In this regards, we develop a nanoextrusion approach to fabricate a multifunctional nanofibrous composite patch capable of addressing the main challenges associated with the healing process of chronic wounds, including i) providing a suitable environment in which cells can easily proliferate and form new blood vessels; ii) preventing or reducing existing bacterial infection using ferumoxytol nanoparticles with and without protein corona; and iii) minimizing unbalanced and prolonged inflammation. We plan to homogeneously incorporate multi-functional biomolecules (e.g., follistatin-like 1, Ac2-26, and ferumoxytol nanoparticles) within its fibrous framework to accelerate angiogenesis and cell proliferation, while minimizing the risk of bacterial infection and prolonged inflammation. A wide range of in-vitro and in-vivo therapeutic efficacy of the novel patches will be conducted. For the in-vivo experiments, we use a rat models of diabetes provided by Charles River to probe the therapeutic and antibacterial efficacy of the patch. Involved mechanisms of the cell and immune system interactions with the multifunctional patch will be identified using a wide range of analysis including advanced electron microscopy. This study will pave the way for the development of new tissue engineering scaffolds to improve the body's natural (endogenous) repair mechanisms by redirecting impaired healing pathways, thus providing a unique opportunity to repair and regenerate damaged skin and tissue in a wide range of chronic wounds.