Proton Sponge Adhesives, Interfacial Milieu: Molecular Structure-Mechanics

描述（由申请人提供）：在美国放置的1.66亿个修复体中，临床数据显示bb0.1亿个是替换体。替代疗法预计将随着复合材料修复需求的增长而增加，例如，根据2009-2013年NIDCR战略计划，牙科复合材料的平均替代时间为5.7年。NIDCR战略计划强调开发更持久的修复体，并研究口腔生物膜是否会加速牙齿复合材料的降解，导致二次腐烂和修复失败。复合修复体的牙龈边缘特别容易腐烂，在这个边缘，粘合剂及其与牙本质的密封提供了预备牙齿与环境之间的主要屏障。致龋细菌变形链球菌与口腔表面的粘附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。牙菌斑生物膜是无法消除的，但通过工程设计的新型抗龋牙本质粘接剂可以降低龈缘生物膜的致病性。我们提出了一种开发粘合剂的双重策略：(i)限制糖蛋白gp340的附着，gp340介导变形链球菌的粘附；（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，甲基丙烯酸酯基粘合剂的配方可以最小化gp340/S。与最先进的蚀刻和冲洗牙本质粘合剂相比，Mutans的附着和中和酸性微环境将提供增强的龋齿发生屏障。我们的目标是展示甲基丙烯酸酯基粘合剂的化学变化如何导致材料性能的可预测变化(gp340/S。改变附着，对乳酸的反应，机械性能)，并基于动力学，疲劳和界面损伤建模来优化原位粘合剂/牙本质键形成的特征。具体目标是：1)合成最有前途的甲基丙烯酸酯基胶粘剂，使gp340/S最小。利用迭代组合优化/合成方法改变附着并中和酸性微环境；2)通过研究降解后的牙本质粘接剂与gp340、变形链球菌的相互作用，确定生物污染对新型牙本质粘接剂降解的影响；3)测试gp340/S的机械和物理化学性能。在无龋齿和受龋齿影响的牙本质的界面上变形抗粘接剂。

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.