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

通过自组装聚合物多层屏障增强口腔组织修复

• 批准号: 7739064
• 负责人: Thomas Dean Dziubla
• 金额: $ 11.04万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739064
• 关键词: Adhesions; Affect; Affinity; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Antioxidants; Aphthous Stomatitis; Area; Attenuated; Binding; Biochemical; Biotin; Chronic; Clinical; Development; Diet Habits; Disease; Drug Formulations; Enzymes; Epitopes; Ethylene Glycols; Evaluation; Event; Fatigue; Fibrin; Film; Friction; Future; Goals; Grant; Growth Factor; Healed; Human; Implant; In Situ; In Vitro; Infection; Inflammation; Injury; Mechanics; Mediating; Methodology; Methods; Modeling; Modification; Molecular; Mucositis; Mus; Natural regeneration; Oral; Oral cavity; Outcome; Oxidative Stress; Pain; Patients; Peptides; Periodontal Diseases; Periodontitis; Pharmaceutical Preparations; Polymers; Principal Investigator; Property; Resistance; Saliva; Series; Site; Solutions; Streptavidin; Surface; System; Testing; Therapeutic; Time; Tissue Grafts; Tissues; Wound Healing; antioxidant therapy; aqueous; catalase; copolymer; crosslink; density; design; ethylene glycol; healing; improved; maxillofacial; methacrylic acid; nanocarrier; nanocomposite; oral tissue; premature; prevent; public health relevance; reconstruction; repaired; response; soft tissue; stability testing

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.

描述（由申请人提供）：慢性软组织口腔伤口（例如，粘膜炎、口疮性口炎和牙周病）可能非常痛苦，并且通常需要开发一种简单的聚合物屏障来增强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，其可以通过纤维蛋白靶向在损伤部位自组装，可以形成屏障，其充当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。在该项目中，我们建议合成原位自组装、逐层聚合物薄膜，为未来输送抗氧化剂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，从而缩短愈合时间，改善各种口腔修复和再生疗法。将合成聚（乙二醇）-g-聚（甲基丙烯酸）和聚（甲基丙烯酸）的官能化聚合物，并对其进行系统评价，以确定逐层屏障组装中的关键参数。这些聚合物将通过肽修饰和生物素-链霉亲和素结合使用纤维蛋白靶向，用于逐层组装。将使用放射性示踪法测试屏障在人唾液存在下的生化稳定性。将使用静态载荷和循环接触力学模型测试机械屏障稳定性。将使用统计设计方法确定影响屏障强度和靶向的关键参数（例如聚合物MW、层数、靶向部分官能化程度）。具体目标：1.）逐层屏障组件的设计与合成。2.）的情况。逐层屏障稳定性的体外评价。 公共卫生关系：该项目的目标是开发一种靶向聚合物系统，可用于形成一种易于应用的自组装屏障，用于治疗口腔伤口和溃疡。通过一系列使用补充聚合物溶液的简单口腔冲洗，可以形成牢固的持久屏障，其可以装载药物以加速愈合时间。据信，这些屏障将可用于治疗患有口腔溃疡如粘膜炎的极端病例的患者。