Im/Miscible Adhesive/Dentin Interface: Structure/Mechanic

摘要 在美国每年2.9亿次牙科治疗中，2亿是失败的替代品 道歉随着公众对替代疗法的关注， 汞和牙科汞合金迫使牙医选择替代材料，例如复合材料。中度至较大 复合牙列的失败率更高，更容易复发龋齿， 更换.中大型II类复合材料置换的临床寿命缩短可能是 这对我们的病人尤其有害，因为切除这些赘生物会导致大量的 健全的牙齿结构，同时需要扩大，更复杂的牙齿矫正， 牙齿脱落在体内条件下，粘合剂/牙本质（A/D）结合可以是对物质的第一防御 渗透并破坏复合修复体我们最近在原位表征的分子 结构和微观力学的a/d接口表明了严重的限制，即物理分离， 在脱矿牙本质中与水混合后形成粘合剂。关键的二甲基丙烯酸酯（BisGMA）， 对交联粘合剂贡献最大的组分渗透了一部分湿的、脱矿物质的粘合剂。 牙本质在这次修订后的竞争性续期申请中，我们建议在我们的成果基础上开发一个水- 通过解决a/d键的下一个化学“阿喀琉斯之踵”（即，a/d键中的酯键）， 甲基丙烯酸酯基体。总的假设是，在潮湿的临床相关牙本质的存在下， 对于基材，配制成水相容性和耐酯酶的甲基丙烯酸酯基粘合剂将 提供增强的界面结构完整性和增加的耐久性。我们的目标是阐明 在临床相关条件下，化学变化将导致牙本质的可预测变化， 粘合剂材料性能（结构、界面行为、机械性能和耐久性）， 基于界面的动力学、生物相容性和建模优化原位A/D键形成的特征 损害具体目标是：1）设计合成最有前途的抗酯酶、抗水- 使用迭代组合优化/合成方法的相容的基于甲基丙烯酸酯的粘合剂; 2） 评价和测试的物理化学，机械和结构性能的酯酶抗性，水， 在与临床相关基质的界面处使用相容的甲基丙烯酸酯基粘合剂， 3）评价牙本质与抗酯酶、抗水- 相容的甲基丙烯酸酯基粘合剂， 结构和牙本质结合可以建立。项目说明 在美国每年进行的2.9亿次牙科治疗中，有2亿次是为了替换 失败的替代疗法1，这种对替代疗法的重视预计将随着公众的关注而增长。 关于牙科汞合金汞释放的问题迫使牙医选择替代材料，例如复合材料 树脂在体内条件下，粘合剂/牙本质粘结可以是抵抗物质的第一道防线， 渗透并破坏复合修复体。如果我们成功地完成了 该项目对患者的直接益处将是：1）大幅度减少这些成分， 降解释放未反应组分的粘合剂体系和2）开发 与潮湿的口腔环境相容，因此更能抵抗过早降解， 破坏了复合结构。

Abstract Out of 290 million dental restorations placed/year in the U.S., 200 million are replacements for failed restorations. This emphasis on replacement therapy is expected to grow as the public's concern regarding mercury and dental amalgam forces dentists to select alternative materials, e.g. composite. Moderate to large composite restorations have higher failure rates, more recurrent caries and increased frequency of replacement. The reduced clinical lifetime of moderate to large class II composite restorations can be particularly detrimental for our patients because removal of these restorations can lead to extensive loss of sound tooth structure with the concomitant need for enlarged, more complex restorations and eventually total tooth loss. Under in vivo conditions the adhesive/dentin (a/d) bond can be the first defense against substances that penetrate and undermine the composite restoration. Our recent in situ characterization of the molecular structure and micro-mechanics of the a/d interface indicated a serious limitation, i.e. physical separation of adhesive upon mixing with water in the demineralized dentin. The critical dimethacrylate (BisGMA), the component contributing the most to the crosslinked adhesive, infiltrated a fraction of the wet, demineralized dentin. In this revised competitive renewal application, we propose to build upon our results to develop a water- compatible adhesive by addressing the next chemical "Achilles heel" of the a/d bond, i.e. ester linkages in the methacrylate matrix. The overall hypothesis is that in the presence of moist clinically relevant dentin substrates, methacrylate-based adhesives formulated to be water-compatible and esterase-resistant will provide enhanced interfacial structural integrity and increased durability. Our goal is to elucidate how alterations in the chemistry will lead, under clinically relevant conditions, to predictable changes in dentin adhesive material properties (structure, interfacial behavior, mechanical properties and durability) and to optimize features for in situ a/d bond formation based on kinetics, biocompatibility and modeling of interfacial damage. The specific aims are: 1) to design and synthesize the most promising esterase-resistant, water- compatible methacrylate-based adhesives using an iterative combinatorial optimization/synthesis approach; 2) to evaluate and test the physicochemical, mechanical and structural properties of the esterase-resistant, water- compatible methacrylate-based adhesives at the interface with such clinically relevant substrates as caries-free and -affected dentin; 3) to evaluate the bond strengths between dentin and esterase-resistant, water- compatible methacrylate-based adhesives so that specific and quantifiable relationships between molecular structure and dentin bonding can be established. Project narrative Out of 290 million dental restorations placed annually in the United States, 200 million are replacements for failed restorations 1 and this emphasis on replacement therapy is expected to grow as the public's concern about mercury release from dental amalgam forces dentists to select alternative materials, e.g. composite resin. Under in vivo conditions the adhesive/dentin bond can be the first defense against substances that penetrate and undermine the composite restoration. If we are successful at completing the goals outlined in this project the direct benefits to the patient will be: 1) a substantial reduction in those components of the adhesive system that degrade releasing unreacted components and 2) development of adhesive systems that are compatible with the wet oral environment and thus, more resistant to premature degradation which undermines composite restorations.