Enhanced Oral Tissue Repair via Self Assembled Polymer Multi-layer Barriers for t

描述（由申请人提供）：慢性口腔软组织伤口（例如，粘膜炎，口腔炎和牙周病）可能非常痛苦，通常需要开发一种简单的应用聚合物屏障来增强这些口腔伤口的愈合。假设用聚合物水溶液冲洗口腔，它可以通过纤维蛋白靶向在损伤部位自组装，有可能形成一个屏障，作为持续抗氧化治疗的平台，通过抑制慢性炎症来改善伤口愈合。在这个项目中，我们建议合成原位自组装，一层一层的聚合物薄膜，为未来抗氧化剂的输送提供保护屏障和平台，用于治疗局部氧化应激介导的组织损伤，从而减少愈合时间，改善各种口腔修复和再生疗法。将合成聚乙二醇-聚甲基丙烯酸和聚甲基丙烯酸的功能化聚合物，并对其进行系统评价，以确定识别层间屏障组装中的关键参数。这些聚合物将通过肽修饰使用纤维蛋白靶向，生物素-链亲和素结合进行逐层组装。在人类唾液存在的情况下，屏障的生化稳定性将用放射性示踪法进行测试。机械屏障稳定性将使用静载荷和循环接触力学模型进行测试。影响屏障强度和靶向的关键参数（例如聚合物分子量，层数，目标部分功能化程度）将使用统计设计方法确定。具体目标：1)逐层屏障组件的设计与合成。2)。逐层屏障稳定性的体外评价。

DESCRIPTION (provided by applicant): Chronic soft tissue oral wounds (e.g., Mucositis, aphthous stomatitis and periodontal disease) can be very painful and often are to develop a simple to apply polymeric barrier for the enhanced healing of these oral wounds. It is hypothesized that by rinsing the oral cavity with an aqueous polymeric solution, which can self assemble at the site of injury via fibrin targeting, it is possible to form a barrier that act as a platform for the sustained antioxidant therapy improving wound healing by suppressing chronic inflammation. In this project we propose to synthesize In-situ self assembled, layer by layer polymers films providing a protective barrier and a platform for future delivery of antioxidants for the treatment of local oxidative stress mediated tissue damage thereby reducing healing time improving a wide variety of oral repair and regeneration therapies. Functionalized polymers of Poly(ethylene glycol)-g-poly(methacrylic acid) and poly(methacrylic acid) will be synthesized and systematically evaluated to determine identify key parameters in the layer by layer barrier assembly. These polymers will use fibrin targeting via peptide modification, and biotin-streptavidin binding for layer by layer assembly. The biochemical stability of the barriers in the presence of human saliva will be tested using radiotracing. Mechanical barrier stability will be tested using a static load and cyclic contact mechanical model. Key parameters affecting barrier strength and targeting (e.g. polymer MW, number of layers, degree of target moiety functionalization) will be identified using a statistical design approach. Specific Aims: 1.) Design and synthesis of layer-by-layer barrier assemblies. 2.) In vitro evaluation of layer-by-layer barrier stability. PUBLIC HEALTH RELEVANCE: This project's goal is to develop a targetable polymer system which can be used to form an easy to apply self assembled barrier for the treatment of oral wounds and sores. Through a series of simple mouth rinses using complementary polymer solutions, a strong persistent barrier which can be loaded with drugs to accelerate healing times can be formed. It is believed that these barriers will be useful in treating patients with extreme cases of oral sores such as Mucositis.