Peptide-coated skin substitutes for the treatment of burn injuries and wounds

描述(由申请人提供)：烧伤和慢性伤口给患者和美国医疗保健系统带来了巨大的负担。在美国，每年有45万例烧伤需要治疗，4.5万名烧伤患者需要住院治疗。与严重烧伤相关的死亡率可能高达10%，75%的患者死亡是由感染引起的。除了感染的风险外，延迟关闭烧伤创面还会延长疼痛，增加肥厚性瘢痕形成或移植物排斥的机会，并成倍增加手术次数。与此同时，静脉性溃疡发生在60万至150万美国患者中，其中35%至45%的患者对目前的治疗没有反应。此外，15%至20%的糖尿病患者将遭受慢性足部伤口，其中高达27%的伤口最终将需要截肢。干细胞可以通过加速血管形成和胶原沉积的速度以及通过减轻炎症反应来满足烧伤和创伤治疗中未得到满足的需求。脂肪来源的间充质干细胞(ASCs)和骨髓来源的间充质干细胞(BMSCs)分泌广泛的蛋白质，对新生血管、细胞外基质(ECM)重塑和炎症反应的减弱至关重要。多项临床前和临床研究报告表明，ASCs和BMSCs可促进烧伤创面和急、慢性创面的愈合。然而，使用扩增和培养的细胞增加了医疗程序的时间和成本，并可能延误治疗。因此，一种能够在护理点从自体组织中捕获ASCs或BMSCs的产品将比使用培养细胞具有显著的优势。在这个项目中，我们建议开发一种用于皮肤替代品的多肽涂层，以在护理点捕获和保留ASCs。当用于治疗慢性伤口和严重烧伤时，这种多肽涂层皮肤替代品将加速血管形成和愈合，并为患者提供实质上更好的结果。

DESCRIPTION (provided by applicant): Burn injuries and chronic wounds present a significant burden to patients and the US healthcare system. Each year in the US, there are 450,000 burns that require medical treatment and 45,000 burn patients that require hospitalization. The mortality rate associated with severe burns can be as high as 10%, with 75% of patient deaths arising from infection. In addition to the risk of infection, delays in burn wound closure prolong pain, increase the chance of hypertrophic scarring or graft rejection, and multiply the number of operative procedures. Meanwhile, venous ulcers occur in 600,000 to 1,500,000 US patients, and 35-45% of these patients will not respond to current treatments. In addition, 15% to 20% of patients with diabetes will suffer a chronic foot wound, and up to 27% of these wounds will eventually require amputation. Stem cells can address the unmet needs in burn and wound therapy by accelerating the rate of vascularization and collagen deposition and by attenuating the inflammatory response. Adipose-derived mesenchymal stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BMSCs) secrete a broad range of proteins that are crucial for neovascularization, extracellular matrix (ECM) remodeling, and the attenuation of an inflammatory response. Multiple pre-clinical and clinical reports suggest that ASCs and BMSCs improve healing of burn injuries and acute and chronic wounds. However, the use of expanded and cultured cells increases the time and cost of medical procedures and can delay treatment. Therefore, a product that can capture ASCs or BMSCs from autologous tissue at the point-of-care would have significant advantages over the use of cultured cells. In this project, we propose to develop a peptide coating for skin substitutes to capture and retain ASCs at the point-of- care. When used to treat chronic wounds and severe burns, the peptide-coated skin substitute will accelerate vascularization and healing and provide substantially better outcomes for patients.