A collagen wound dressing augmented with a proteoglycan mimic to enhance chronic

描述（由申请人提供）：本提案针对NIH， CDC， FDA和ACF的小企业创新研究资助申请的PHS 2012-02综合征集（母SBIR [R43/R44]）。在美国，慢性伤口每年影响650万人，占所有发达国家人口的1% -2%，仅在美国，每年的治疗费用就高达250亿美元。老年人口的增加，加上糖尿病和肥胖症发病率的上升，预计将推动慢性伤口市场的增长。慢性伤口具有高水平的炎症活性，特别是基质金属蛋白酶（MMPs），导致慢性伤口细胞外基质的高周转率。慢性伤口也经常处于缺血状态，因为血管减少。慢性伤口环境中MMP活性的增加、血管的减少和ECM产生的不稳定都会导致持续的皮肤退化和随后的溃疡。提供外源性组织工程支架，如基于胶原蛋白的ECM，在治疗不愈合伤口方面取得了一些临床成功，因为它们能够提供结合并增加活性生长因子的底物。然而，现有的产品在慢性伤口的腐蚀性环境中可能会过早降解，并且通常不能实现促进伤口愈合所需的细胞浸润、血管生成和上皮化。Glytrix已经

DESCRIPTION (provided by applicant): This proposal addresses PHS 2012-02 Omnibus Solicitation of the NIH, CDC, FDA and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44]). Chronic wounds affect 6.5 million people in the US each year, and 1-2% of the population in all developed countries, with treatment costs in the US alone reaching $25 billion annually. The increasing elderly population, in addition to the rising rates of diabetes and obesity, is expected to drive growth in the chronic wound market. Chronic wounds have a high level of inflammatory activity, specifically matrix metalloproteinases (MMPs) that leads to high turnover of the extracellular matrix in a chronic wound. Chronic wounds also are often in an ischemic state, due to decreased vascularity. The increased MMP activity, decreased vascularity, and unstable ECM production in a chronic wound environment all lead to continued skin degradation and subsequent ulceration. Providing an exogenous tissue engineered scaffold, such as a collagen based ECM, has shown some clinical success in treating nonhealing wounds due to their ability to provide a substrate that can bind and increase the activity of resident growth factors. However, existing products can be prematurely degraded in the caustic environment of the chronic wound, and often do not achieve the necessary cellular infiltration, angiogenesis, and epithelialization to facilitate wound healing. Glytrix has developed a synthetic proteoglycan called DS-SILY. The molecule, inspired by the native proteoglycan decorin, is composed of a dermatan sulfate (DS) backbone with attached collagen binding peptides (SILY). This proteoglycan mimic has been shown to: 1) bind to and protect collagen scaffolds from MMP degradation; 2) promote the proliferation of both endothelial cells and keratinocytes; and 3) decrease granulation tissue and visible scarring and increase tensile strength after incisional wounding in a rat model. These characteristics have led to the hypothesis that augmentation of a collagen scaffold with DS-SILY will lead to slower degradation of the scaffold in the chronic wound environment, and will increase vascularity and epithelialization of the wound by potentiating resident growth factors, resulting in more effective healing of chronic wounds as compared to a collagen scaffold alone. Due to their different biological activities, two DS-SILY molecules with varying molecular weights will be examined in combination with a collagen dressing in a rat model of delayed healing. Wound healing markers will include epithelializaton, inflammation, tissue remodeling, and matrix degradation and deposition. Successful completion of this Phase I SBIR will result in a single DS-SILY molecule that will move forward in development by testing biocompatibility of the molecule as required by the FDA. GMP synthesis, biocompatibility testing, and a small clinical safety study will be the milestones for a Phase II award.