A Nanostructured Skin Patch to Heal Chronic Wounds

用于治愈慢性伤口的纳米结构皮肤贴片

• 批准号: 10548827
• 负责人: Morteza Mahmoudi
• 金额: $ 40.8万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548827
• 关键词: Acceleration; Address; Affect; Amputation; Anti-Bacterial Agents; Antibiotic Resistance; Automobile Driving; Bacterial Infections; Blood Vessels; Cell Proliferation; Cells; Chitosan; Chondroitin Sulfates; Chronic; Cicatrix; Clinical; Coculture Techniques; Collagen; Complex; Development; Devices; Diabetic Foot Ulcer; Ecosystem; Electron Microscopy; Environment; Epithelium; Exposure to; Exudate; FDA approved; Follistatin; Foot Ulcer; Foundations; Funding; Goals; Hyaluronic Acid; Immune response; Immune system; Impaired healing; Impairment; In Vitro; Infection; Inflammation; Inflammation Mediators; Innovation Corps; Interview; Leg Ulcer; Libraries; Liquid substance; Macrophage; Macrophage Activation; Mammalian Cell; Measures; Medical; Membrane; Metalloproteases; Microbial Biofilms; Modeling; Molecular; Morbidity - disease rate; Nanostructures; Nanotechnology; Natural regeneration; Patch Tests; Pathway interactions; Patients; Peptides; Polymers; Polysaccharides; Predisposition; Prevention; Process; Proliferating; Property; Proteins; Rattus; Research; Research Project Grants; Role; Science; Site; Skin; Social Responsibility; Staphylococcus aureus; Sterile coverings; Surface; System; Testing; Therapeutic; Tissue Engineering; Tissues; Treatment Efficacy; United States; Venous; Wound Infection; Wound healing therapy; angiogenesis; chronic wound; clinically relevant; clinically significant; cost; design; diabetic rat; diabetic ulcer; effective therapy; experimental study; ferumoxytol; healing; improved; in vivo; in vivo evaluation; iron oxide nanoparticle; migration; mortality; multidisciplinary; nanofiber; nanoparticle; nanoparticle exposure; nanoscale; non-healing wounds; novel; prevent; programs; repaired; risk minimization; scaffold; skin damage; skin patch; success; superparamagnetism; therapeutic patch; wound; wound closure; wound dressing; wound environment; wound healing

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.

摘要 慢性不愈合伤口使人衰弱，具有高发病率和死亡率。这是普遍和昂贵的， 治疗（例如，仅在美国，静脉性腿部溃疡每年约150亿美元）。尽管作出了广泛的努力， 开发有效治疗慢性伤口的治疗策略，迄今为止，有限的临床成功 办妥了一批多年想目前可用的设备和产品仅被设计成针对一个或多个复杂的系统。 慢性伤口中受损的细胞和分子功能。 治疗和治愈慢性皮肤病的临床意义和医学及社会责任日益增加 伤口正在推动对开发有效设计和制造的伤口愈合装置的需求。 一种系统，其不仅具有皮肤的物理机械特性，而且还校正或避免皮肤的老化。 慢性伤口的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出方法来制造一种 多功能纳米纤维复合材料贴片能够解决与 慢性伤口的愈合过程，包括i）提供合适的环境，在该环境中细胞可以容易地 增殖并形成新血管; ii）使用ferumoxytol预防或减少现有的细菌感染 具有和不具有蛋白质冠的纳米颗粒;和iii）最小化不平衡和延长的炎症。我们 计划均匀地掺入多功能生物分子（例如，卵泡抑素样1，Ac 2 -26，和 ferumoxytol纳米颗粒），以加速血管生成和细胞增殖， 最大限度地减少细菌感染和长期炎症的风险。广泛的体外和体内 将对新型贴剂的治疗效果进行研究。对于体内实验，我们使用了大鼠模型， 由Charles River提供的用于糖尿病的贴片，以探测贴片的治疗和抗菌功效。涉及 细胞和免疫系统与多功能贴片相互作用的机制将使用 广泛的分析，包括先进的电子显微镜。 本研究将为开发新的组织工程支架以改善机体的 自然（内源性）修复机制，通过重新定向受损的愈合途径，从而提供了一个独特的 有机会修复和再生各种慢性伤口中受损的皮肤和组织。