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，临床数据表明替代者> 1亿。随着对复合修复体的需求不断增长，例如，替代疗法将增加，例如如2009 - 2013年NIDCR战略计划所示，牙科复合材料的平均替代时间为5。7年。 NIDCR战略计划强调了持续延长的修复体的发展和研究，探索口腔生物膜是否加速了牙科复合材料的降解，从而导致次要衰变和恢复失败。复合修复体的牙龈边缘特别容易衰减，在此边缘，粘合剂及其对牙本质的密封为准备的牙齿和环境之间提供了主要的屏障。牙科链球菌对嘴表面的粘附细菌的粘附会产生一个支持其他细菌物种的附着和生长的环境，最终形成微生物系统，即生物膜。不能消除牙菌斑生物膜，但是通过工程新型的抗钙化牙本质粘合剂可以降低生物膜在牙龈边缘的致病影响。我们提出了一种双重策略，以开发（i）（i）限制糖蛋白GP340的附着的粘合剂，该策略介导了突变链球菌的粘附，并（ii）中和酸性微环境以防止邻近牙齿结构的脱层。这项工作的总体假设是，以甲基丙烯酸酯为基础的粘合剂，以最大程度地减少GP340/s。与最先进的蚀刻剂牙本质粘合剂相比，变形物的附着和中和酸性微环境将提供增强的癌变障碍。我们的目标是展示基于甲基丙烯酸酯的胶粘剂化学的变化如何导致材料特性（GP340/s。Mutans的附着，对乳酸的反应，机械性能）的可预测变化，并优化基于动力学，疲劳和模型的原位粘合剂/牙本质键形成的特征。具体目的是：1）合成最小化GP340/s的最有希望的基于甲基丙烯酸酯的粘合剂。使用迭代组合优化/合成方法，变形剂的附着和中和酸性微环境； 2）通过研究降解的粘合剂，GP340和S. utans之间的相互作用来确定生物结垢对新牙本质粘合剂降解的影响； 3）测试GP340/s的机械和物理化学特性。与无龋齿和受龋齿影响的牙本质的界面处的抗恒变量粘合剂。