Proton Sponge Adhesives, Interfacial Milieu: Molecular Structure-Mechanics

描述（由申请人提供）：在美国的1.66亿个职位中，临床数据表明，> 1亿是替代品。随着对复合材料的需求不断增长，替代治疗预计将增加，例如，如2009-2013年NIDCR战略计划所示，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预防和研究，探讨口腔生物膜是否会加速牙科复合材料的降解，导致二次腐烂和修复失败。复合材料牙本质的牙龈边缘特别容易受到腐蚀，并且在该边缘处，粘合剂及其对牙本质的密封提供了制备的牙齿与环境之间的主要屏障。致龋细菌，变形链球菌，粘附到口腔表面，创造了一个支持其他细菌物种随后附着和生长的环境，最终形成一个微生态系统，即，生物膜。牙菌斑生物膜不能被消除，但生物膜在龈缘的致病性影响可以通过设计新型抗龋牙本质粘合剂来减少。我们提出了一个双重策略来开发粘合剂，（i）限制糖蛋白gp 340的附着，该糖蛋白介导S的粘附。变形菌和（ii）中和酸性微环境以防止相邻牙齿结构的脱矿。这项工作的总体假设是，甲基丙烯酸酯基粘合剂的配方使gp 340/S最小化。与现有技术的蚀刻-冲洗牙质粘合剂相比，变形菌附着和中和酸性微环境将提供对龋齿发生的增强的屏障。我们的目标是展示甲基丙烯酸酯基粘合剂化学性质的改变如何导致材料性能的可预测变化（gp 340/S）。变形菌附着、对乳酸的反应、机械性能），并基于界面损伤的动力学、疲劳和建模来优化原位粘合剂/牙本质粘结形成的特征。具体目标是：1）合成最有前途的甲基丙烯酸酯基粘合剂，使gp 340/S最小化。2）通过研究降解后的牙本质粘接剂gp 340与S. mutans的相互作用，确定生物污损对新型牙本质粘接剂降解的影响。3）测试gp 340/S的机械和物理化学性质。在与无龋和龋影响牙本质的界面处的抗变形菌粘合剂。 公共卫生相关性：2005年，美国有1.66亿例置换术，临床研究表明，其中一半以上是置换失败的置换术。复合牙釉质在5.7年时可能需要更换，这些牙釉质的失效可以追溯到粘合剂/牙本质粘合和致龋细菌变形链球菌在边缘的附着。拟定项目将带来以下患者受益：1）可从粘合剂中释放的未反应组分大幅减少; 2）促进S附着的材料特征大幅减少。变形菌;和3）中和该区域以防止酸引起的对邻近牙齿结构的损伤（空化）的粘合剂。

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.