Therapeutic Antimicrobial Human Skin Substitute

描述（由申请人提供）： 我们建议的最终目标是遗传工程化治疗性人类皮肤替代品，用于治疗皮肤损伤，如皮肤伤口（例如，病理性或创伤性）和溃疡（例如，静脉和糖尿病溃疡）。慢性皮肤溃疡是特别成问题的，因为它们通常被感染，导致伤口愈合受损和并发症增加，具有不期望的后果，如截肢。目前市售的治疗性皮肤替代产品是细胞或无细胞的，并且由补充有原代人角质形成细胞和/或成纤维细胞的基于胶原的基质或人工基质的不同组合组成。这些产品旨在替代或补偿无功能的皮肤。然而，没有一种市售产品经过优化以保护伤口床免受感染。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。人源性的内源性抗微生物肽，如防御素，已经成为一种令人兴奋的新的治疗方法，以增强宿主对入侵微生物的先天防御机制。这为开发创新的、基因增强的人类皮肤替代产品提供了机会，这些产品表达抗微生物肽以保护伤口部位免受细菌侵袭，同时允许角质形成细胞增殖并加速伤口闭合。在过去的一年中，Stratatech公司在专利人类角质形成细胞系的离体基因工程方面取得了进展，使我们能够独特地生产用于烧伤和慢性皮肤创伤市场的基因增强的人类皮肤替代品。

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.