Therapeutic Antimicrobial Human Skin Substitute

治疗性抗菌人类皮肤替代品

• 批准号: 6845566
• 负责人: B LYNN ALLEN-HOFFMANN
• 金额: $ 43.46万
• 依托单位: STRATATECH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845566
• 关键词: antiinfective agents; artificial skin; biomaterial development /preparation; biotechnology; cell line; defensins; genetic manipulation; human genetic material tag; keratinocyte; tissue engineering; wound healing

DESCRIPTION (provided by applicant): The ultimate goal of our proposal is to genetically engineer a therapeutic human skin substitute for use in the treatment of skin lesions such as skin wounds (e.g., pathological or traumatic) and ulcers (e.g., venous and diabetic ulcers). Chronic skin ulcers are particularly problematic as they typically become infected resulting in impaired wound healing and increased complications with undesirable consequences such as amputation. Today's marketed therapeutic skin substitute products are cellular or acellular and composed of varying combinations of collagen-based or artificial matrixes supplemented with primary human keratinocytes and/or fibroblasts. These products have been designed to replace or compensate for non-functioning skin. However, none of the marketed products has been optimized to protect the wound bed from infection. Additionally, cellular skin therapies have been shown to be exquisitely sensitive to the toxic effects of commonly used antimicrobial agents. Human-derived, endogenous antimicrobial peptides, such as the defensins, have emerged as an exciting new therapeutic approach to enhance innate host defense mechanisms against invading microorganisms. This presents an opportunity for the development of innovative, genetically enhanced human skin substitute products which express antimicrobial peptides to defend the wound site from bacterial invasion while allowing keratinocyte proliferation and expediting wound closure. In the last year advances in ex vivo genetic engineering of a patented human keratinocyte cell line at Stratatech Corporation has made us uniquely positioned to generate genetically enhanced human skin substitutes for use in the burn and chronic skin wound market.

描述（由申请人提供）： 我们建议的最终目标是在遗传上设计一种治疗性人体皮肤替代品，用于治疗皮肤病变，例如皮肤伤口（例如病理或创伤性）和溃疡（例如静脉和糖尿病性溃疡）。慢性皮肤溃疡尤其有问题，因为它们通常会被感染，从而导致伤口愈合受损和增加并发症，并产生不良后果，例如截肢。当今销售的治疗性皮肤替代产品是细胞或细胞的，由补充原代人角质形成细胞和/或成纤维细胞的基于胶原蛋白或人工基质的不同组合组成。这些产品旨在替代或补偿非功能性皮肤。但是，尚未对市场产品进行优化，以保护伤口床免受感染。另外，已经证明细胞皮肤疗法对常用抗菌剂的毒性作用非常敏感。人类衍生的内源性抗菌肽（例如防御素）已成为一种令人兴奋的新治疗方法，可增强对侵入微生物的先天宿主防御机制。这为开发创新的，遗传增强的人类皮肤替代产品提供了一个机会，这些产品表达抗菌肽，以防御伤口部位免受细菌侵袭，同时允许角质形成细胞增殖并加快伤口闭合。在去年，StrataTech Corporation的专利人角质形成细胞系的离体基因工程的进步使我们在遗传性增强的人体皮肤替代品中的独特位置，以在燃烧和慢性皮肤伤口市场中使用。