Proton Sponge Adhesives, Interfacial Milieu: Molecular Structure-Mechanics

质子海绵粘合剂，界面环境：分子结构力学

• 批准号: 8161636
• 负责人: Jennifer S. Laurence
• 金额: $ 36.33万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8161636
• 关键词: Acids; Address; Adhesions; Adhesives; Adsorption; Affect; Agglutinins; Area; Bacteria; Bacterial Adhesins; Binding; Cell Wall; Chemistry; Clinical; Clinical Data; Clinical Research; Clinical Services; Dental; Dental Enamel; Dental Pellicle; Dental Plaque; Dental Research; Dental caries; Dentin; Deterioration; Development; Ecosystem; Engineering; Environment; Enzymes; Failure; Fatigue; Film; Fostering; Fracture; Gingiva; Glycoproteins; Goals; Growth; Human; In Situ; Incidence; Inflammation; Kinetics; Lactic acid; Lead; Link; Liquid substance; Mechanics; Mediating; Methacrylates; Microbial Biofilms; Modeling; Molecular Structure; Molecular Weight; National Institute of Dental and Craniofacial Research; Oral; Oral cavity; Organism; Patients; Porifera; Property; Proteins; Protons; Reaction; Recurrence; Replacement Therapy; Research; Resistance; Role; Saliva; Salivary; Secondary to; Simulate; Strategic Planning; Streptococcus mutans; Stress; Surface; Testing; Time; Tooth structure; Viscosity; Work; analog; base; cariogenic bacteria; clinically relevant; combinatorial; composite restoration; demineralization; design; improved; interfacial; microorganism; novel; oral biofilm; prevent; pulpal hypersensitivity; restoration; restorative dentistry; seal; tooth surface

DESCRIPTION (provided by applicant): Out of 166 million restorations placed in the U.S., clinical data suggest that >100 million were replacements. Replacement therapy is expected to increase with the growing demand for composite restorations, e.g. as indicated in the 2009-2013 NIDCR strategic plan, dental composites have an average replacement time of 5.7 years. The NIDCR strategic plan stresses the development of longer-lasting restorations and research that explores whether oral biofilms accelerate the degradation of dental composites, leading to secondary decay and restoration failure. The gingival margin of composite restorations is particularly vulnerable to decay and at this margin, the adhesive and its seal to dentin provides the primary barrier between the prepared tooth and the environment. Adhesion of the cariogenic bacterium, Streptococcus mutans, to surfaces in the mouth creates an environment that supports the subsequent attachment and growth of other bacterial species, ultimately forming a micro-ecosystem, i.e., a biofilm. Dental plaque biofilm cannot be eliminated, but the pathogenic impact of the biofilm at the gingival margin could be reduced by engineering novel anti-cariogenic dentin adhesives. We propose a twofold strategy to develop adhesives that (i) limit attachment of the glycoprotein, gp340, that mediates adhesion of S. mutans and (ii) neutralize the acidic micro-environment to prevent demineralization of the adjacent tooth structure. The overall hypothesis of this work is that methacrylate-based adhesives formulated to minimize gp340/S. mutans attachment and to neutralize the acidic micro-environment will provide an enhanced barrier to cariogenesis as compared to the state-of-the-art etch-and-rinse dentin adhesives. Our goal is to show how alterations in the chemistry of methacrylate-based adhesives will lead to predictable changes in material properties (gp340/S. mutans attachment, reaction to lactic acid, mechanical properties) and to optimize features for in situ adhesive/dentin bond formation based on kinetics, fatigue and modeling of interfacial damage. The specific aims are: 1) to synthesize the most promising methacrylate-based adhesives which minimize gp340/S. mutans attachment and neutralize the acidic micro-environment using an iterative combinatorial optimization/synthesis approach; 2) to determine the effect of biologic fouling on degradation of the new dentin adhesives by studying the interaction between the degraded adhesive, gp340 and S. mutans; 3) to test the mechanical and physicochemical properties of the gp340/S. mutans resistant adhesive at the interface with caries-free and caries-affected dentin. PUBLIC HEALTH RELEVANCE: In 2005, 166 million restorations were placed in the U.S. and clinical studies indicate that more than half were replacement for failed restorations. Composite restorations may require replacement at 5.7 years failure of these restorations has been traced to the adhesive/dentin bond and attachment of the cariogenic bacterium, Streptococcus mutans, at the margin. The proposed project will result in the following patient benefits: 1) a substantial reduction in unreacted components that could be released from the adhesive; 2) a substantial decrease in the material features that promote attachment of S. mutans; and 3) adhesives that neutralize the area to prevent acid-induced damage (cavitation) to the adjacent tooth structure.

描述（由申请人提供）：在美国放置的 1.66 亿个修复体中，临床数据表明超过 1 亿个是替换体。随着复合修复体需求的不断增长，替代疗法预计将会增加，例如复合修复体。根据2009-2013年NIDCR战略计划，牙科复合材料的平均更换时间为5.7年。 NIDCR 战略计划强调开发更持久的修复体和研究，探索口腔生物膜是否会加速牙科复合材料的降解，从而导致继发性腐烂和修复体失败。复合修复体的牙龈边缘特别容易腐烂，在这个边缘，粘合剂及其对牙本质的密封提供了准备好的牙齿和环境之间的主要屏障。致龋菌变形链球菌粘附在口腔表面，创造了一个支持其他细菌随后附着和生长的环境，最终形成一个微生态系统，即生物膜。牙菌斑生物膜无法消除，但可以通过设计新型防龋牙本质粘合剂来减少牙龈边缘生物膜的致病影响。我们提出了开发粘合剂的双重策略，该策略（i）限制介导变形链球菌粘附的糖蛋白 gp340 的附着，以及（ii）中和酸性微环境以防止邻近牙齿结构脱矿质。这项工作的总体假设是甲基丙烯酸酯基粘合剂的配方可最大限度地减少 gp340/S。与最先进的蚀刻和冲洗牙本质粘合剂相比，变形链球菌的附着和中和酸性微环境将为龋齿形成提供增强的屏障。我们的目标是展示基于甲基丙烯酸酯的粘合剂的化学变化将如何导致材料性能（gp340/S. mutans 附着、对乳酸的反应、机械性能）的可预测变化，并基于动力学、疲劳和界面损伤建模优化原位粘合剂/牙本质粘合形成的特征。具体目标是：1）合成最有前途的甲基丙烯酸酯基粘合剂，使 gp340/S 最小化。使用迭代组合优化/合成方法附着变形链球菌并中和酸性微环境； 2) 通过研究降解的粘合剂、gp340和变形链球菌之间的相互作用，确定生物污垢对新型牙本质粘合剂降解的影响； 3）测试gp340/S的机械和理化性能。与无龋齿和受龋齿影响的牙本质界面处的抗变形粘合剂。 公共健康相关性：2005 年，美国安装了 1.66 亿个修复体，临床研究表明，其中一半以上是失败修复体的替换体。复合修复体可能需要在 5.7 年时更换，这些修复体的失败可追溯到边缘处的粘合剂/牙本质粘合和致龋菌变形链球菌的附着。拟议的项目将为患者带来以下好处：1）大幅减少粘合剂中可能释放的未反应成分； 2) 促进变形链球菌附着的物质特征大幅减少； 3) 中和该区域的粘合剂，以防止酸对邻近牙齿结构造成损害（空化）。