Antimicrobial, Angiogenic Skin Substitutes for Diabetic*

描述(由申请人提供)： 这项应用的目标是开发一种具有增强的抗菌和血管生成特性的基因工程治疗性人类皮肤替代品，用于治疗1型糖尿病皮肤溃疡。慢性糖尿病皮肤溃疡表现为血流不畅，通常会被感染，导致伤口愈合受损和截肢，这是糖尿病的一种危及生命的并发症。对慢性、感染、无法愈合的糖尿病伤口的标准护理是抗生素治疗和合成敷料。由于通常遇到的细菌菌株经常对抗生素产生抗药性，特别是在慢性伤口，临床医生仅限于使用更有效的抗生素，这些抗生素会对糖尿病皮肤溃疡中细胞的活性和迁移产生不良影响。这一点，加上对出现的新的多重耐药菌株的日益关注，突显了需要创新的方法来补充开放伤口治疗中使用的抗生素治疗制度。 Stratech公司促进感染的糖尿病皮肤溃疡的伤口愈合的战略是开发一种新型的人类皮肤替代品，具有一系列增强的抗菌、再上皮化和血管形成特性。我们的FastTrack SBIR提案概述了生成人类皮肤替代品的成熟策略，这些替代品经过基因工程，能够分泌具有生物活性的抗菌肽(AMPs)，能够刺激血管形成和细胞迁移。1型糖尿病和慢性创面愈合的动物模型将被用来检验这样的假设，即含有人AMP表达细胞的人皮肤替代组织将防止慢性创面感染，促进再上皮化和血管生成，从而为糖尿病创面的愈合提供最佳环境。Stratech Corporation获得专利的人类角质形成细胞系体外基因工程的进展使我们这家年轻的公司处于独特的地位，可以生产用于治疗1型糖尿病皮肤溃疡的基因增强型人类皮肤替代品。

DESCRIPTION (provided by applicant): The goal of this application is to develop a genetically engineered therapeutic human skin substitute with enhanced antimicrobial and angiogenenic properties for use in the treatment of type 1 diabetic skin ulcers. Chronic diabetic skin ulcers exhibit poor blood flow and typically become infected resulting in impaired wound healing and amputation, a life threatening complication of diabetes. The standard of care for chronic, infected, nonhealing diabetic wounds is antibiotic treatment and synthetic dressings. Because bacterial strains typically encountered often become antibiotic resistant, especially in the chronic wound, the clinician is limited to more potent antibiotics with undesirable effects on viability and migration of cells in the diabetic skin ulcer. This, coupled with the growing concern over emerging new multi-resistant strains of bacteria, underscores the need for innovative approaches to supplement antibiotic treatment regimes used in open wound therapy. Stratatech Corporation's strategy to promote wound healing in infected diabetic skin ulcers is to develop a novel human skin substitute possessing a range of enhanced antimicrobial, re-epithelialization, and vascularization properties. Our FastTrack SBIR proposal outlines proven strategies for the generation of human skin substitutes genetically engineered to secrete biologically active antimicrobial peptides (AMPs) capable of stimulating vascularization and cell migration. Animal models of type 1 diabetes and chronic wound healing will be used to test the hypothesis that a human skin substitute tissue containing human AMPexpressing cells will prevent chronic wound infection, facilitate re epithelialization, and vascularization, and thus provide an optimal environment for the healing of diabetic wounds. Advances in ex vivo genetic engineering of a patented human keratinocyte cell line at Stratatech Corporation has made our young company uniquely positioned to generate genetically enhanced human skin substitutes for use in the treatment of type 1 diabetic skin ulcers.