Therapeutic Antimicrobial Human Skin Substitute

描述（由申请人提供）： 我们提案的最终目标是通过基因工程设计一种治疗性人类皮肤替代品，用于治疗皮肤损伤，例如皮肤伤口（例如病理性或创伤性）和溃疡（例如静脉性和糖尿病性溃疡）。慢性皮肤溃疡尤其成问题，因为它们通常会受到感染，导致伤口愈合受损并增加并发症，从而导致截肢等不良后果。当今市售的治疗性皮肤替代产品是细胞或非细胞的，由胶原基或人工基质的不同组合组成，并补充有原代人角质形成细胞和/或成纤维细胞。这些产品旨在替代或补偿无功能的皮肤。然而，市面上的产品都没有经过优化来保护创面床免受感染。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，可增强宿主针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，这些产品表达抗菌肽，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。去年，Stratatech 公司在获得专利的人类角质形成细胞系的离体基因工程方面取得了进展，使我们在生产用于烧伤和慢性皮肤伤口市场的基因增强型人类皮肤替代品方面处于独特的地位。

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.