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

描述(申请人提供)：慢性口腔软组织伤口(如粘膜炎、口腔炎和牙周病)可能非常痛苦，通常需要形成一种简单的聚合物屏障来促进这些口腔伤口的愈合。据推测，通过用聚合物水溶液冲洗口腔，这种聚合物溶液可以通过纤维蛋白靶向在损伤部位自组装，有可能形成一种屏障，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的逐层聚合物薄膜，提供保护屏障和未来输送抗氧化剂的平台，用于治疗局部氧化应激介导的组织损伤，从而缩短愈合时间，改进各种口腔修复和再生疗法。将合成聚乙二醇接枝聚甲基丙烯酸和聚甲基丙烯酸功能化聚合物，并对其进行系统评价，以确定逐层屏障组装中的关键参数。这些聚合物将通过多肽修饰使用纤维蛋白靶向，并通过生物素-链霉亲和素结合进行逐层组装。在人类唾液存在的情况下，将使用放射性示踪法测试屏障的生物化学稳定性。机械屏障的稳定性将使用静载和循环接触力学模型进行测试。将使用统计设计方法确定影响阻隔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)。具体目标：1.)层层屏障组件的设计和合成。2.)层层屏障稳定性的体外评价。 与公共卫生相关：该项目的目标是开发一种有针对性的聚合物系统，可以用来形成一种易于应用的自组装屏障，用于治疗口腔创伤和溃疡。通过使用互补聚合物溶液的一系列简单的漱口水，可以形成一种强大的持久性屏障，可以装载药物来加速愈合时间。人们相信，这些屏障将有助于治疗粘膜炎等口腔溃疡的极端病例。

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.