Therapeutic Antimicrobial Human Skin Substitute

描述(由申请人提供)： 我们建议的最终目标是从基因上设计一种治疗性的人类皮肤替代品，用于治疗皮肤损伤，如皮肤创伤(例如，病理性或创伤性)和溃疡(例如，静脉和糖尿病溃疡)。慢性皮肤溃疡的问题尤其严重，因为它们通常会受到感染，导致伤口愈合受损，并发症增加，导致截肢等不良后果。当今市场上的治疗性皮肤替代品产品是细胞或无细胞的，由胶原基或人工基质与原代人类角质形成细胞和/或成纤维细胞补充的不同组合组成。这些产品旨在取代或补偿不起作用的皮肤。然而，市场上没有一种产品经过优化，可以保护伤口床不受感染。此外，细胞皮肤疗法已被证明对常用抗菌剂的毒性作用非常敏感。人类来源的内源性抗菌肽，如防御素，已经成为一种令人兴奋的新的治疗方法，以增强对入侵微生物的固有宿主防御机制。这为创新的、基因增强型人类皮肤替代品产品的开发提供了机会，这些产品表达抗菌肽，以保护伤口部位免受细菌入侵，同时允许角质形成细胞增殖并加快伤口闭合。去年，Stratech Corporation在获得专利的人类角质形成细胞系的体外基因工程方面取得的进展使我们处于独特的地位，可以生产用于烧伤和慢性皮肤创伤市场的基因增强型人类皮肤替代品。

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.