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重大负担。在美国，每年有45万例烧伤需要治疗，4.5万例烧伤需要住院治疗。慢性伤口最常见的原因之一，静脉溃疡，发生在60万至150万美国患者；15%到20%的糖尿病患者会有慢性足部伤口。对于烧伤，死亡率可高达10%，其中75%的患者死亡是由感染引起的。烧伤后感染风险的增加可归因于多种因素，包括伤口愈合缓慢。除了感染的风险外，烧伤伤口愈合的延迟延长了疼痛，增加了肥厚性瘢痕形成的机会，并增加了手术次数。干细胞可以通过加速血管形成和胶原沉积的速度以及减轻炎症反应来解决烧伤治疗中未满足的需求。脂肪源性间充质干细胞（ASCs）和骨髓源性间充质干细胞（BMSCs）分泌多种蛋白质，这些蛋白质对新生血管、细胞外基质（ECM）重塑和炎症反应的衰减至关重要。多项临床前和临床报告表明，ASCs和骨髓间充质干细胞可以改善烧伤和急慢性伤口的愈合。然而，使用扩增和培养的细胞会增加医疗程序的时间和费用，并可能延迟治疗。因此，一种能够在护理点从自体组织中捕获大量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肽涂层，以在护理点捕获和保留ASCs。当用于替换受损皮肤时，肽包被的皮肤替代品将加速血管化和愈合，并为患者提供更好的结果。

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 burns that require hospitalization. One of the most common causes of chronic wounds, venous ulcers, occurs in 600,000 to 1,500,000 US patients; 15% to 20% of patients with diabetes will suffer a chronic foot wound. For burn injuries, the mortality rate can be as high as 10%, with 75% of patient deaths arising from infection. Increased risk of infection after burn injury can be attributed to multiple factors including slow wound healing. In addition to the risk of infection, delays in burn wound closure prolong pain, increase the chance of hypertrophic scarring, and multiply the number of operative procedures. Stem cells can address the unmet needs in burn 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 large numbers of 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 replace damaged skin, the peptide-coated skin substitute will accelerate vascularization and healing and provide substantially better outcomes for patients. PUBLIC HEALTH RELEVANCE: Project Narrative Adult stem cells provide numerous advantages to speed up the process of healing of burn injuries and wounds. In this application, we propose to modify skin substitutes with a coating that will allow surgeons to capture adult stem cells onto the skin substitute during the operation. This cell capture will reduce the costs o processing cells, and the delivery of high numbers of therapeutic cells will provide better and faster healing.