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: 8288703
• 负责人: Jennifer S. Laurence
• 金额: $ 36.3万
• 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/8288703
• 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.

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&gt；1亿个是替换物。随着对复合修复体不断增长的需求，替代疗法有望增加，例如，正如2009-2013年NIDCR战略计划所指出的，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和研究，探索口腔生物膜是否会加速牙科复合材料的降解，导致二次龋齿和修复失败。复合修复体的牙龈边缘特别容易腐烂，在这一边缘，粘结剂及其对牙本质的密封在准备好的牙齿和环境之间提供了主要的屏障。致龋性细菌变形链球菌与口腔表面的黏附创造了一个支持其他细菌物种随后附着和生长的环境，最终形成了一个微生态系统，即生物膜。牙菌斑生物膜不能被消除，但可以通过设计新型的防龋牙本质粘结剂来减少牙菌斑生物膜对牙周边缘的致病影响。我们提出了一种双重策略来开发粘合剂，这种粘合剂(I)限制糖蛋白gp340的附着，gp340介导变形链球菌的黏附，以及(Ii)中和酸性微环境以防止邻近牙齿结构的脱矿。这项工作的总体假设是，与最先进的酸蚀和漂洗牙本质粘合剂相比，旨在最大限度地减少gp340/变形链球菌附着并中和酸性微环境的甲基丙烯酸酯粘接剂将提供更强的防龋性屏障。我们的目标是展示甲基丙烯酸酯粘接剂的化学变化如何导致材料性能(gp340/变形链球菌的附着、对乳酸的反应、机械性能)的可预测变化，并基于动力学、疲劳和界面损伤模拟来优化原位粘结剂/牙本质粘结形成的特征。其具体目标是：1)通过迭代组合优化/合成方法，合成最有希望的甲基丙烯酸酯基粘接剂，最大限度地减少gp340/变形链球菌的附着，并中和酸性微环境；2)通过研究降解的粘结剂gp340与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接剂降解的影响；3)测试gp340/变形链球菌抗牙本质粘接剂与无龋牙本质和有龋牙本质界面的力学和物理化学性能。