Tertiary methacrylamides and thiourethane additives as novel dental composites

摘要 患者和牙医对美容牙科修复体的需求不断增加，刺激了 树脂复合材料的改进。目前，这些材料被用于绝大多数直接、座椅侧 每年都会进行修复。然而，水解和酶攻击与聚合一起 收缩，对牙齿和修复体之间的粘结界面构成了挑战，从而减少了 修复体的寿命和可靠性。本研究提出合成新型叔甲基丙烯酰胺 用作牙科复合材料和粘合剂的有机基质的单体，完全脱离 几乎所有目前的材料都使用传统的甲基丙烯酸酯化学。这种单体体系非常适合于 这一应用因为它具有耐水解性和耐酶侵性，而且还可以原位聚合 在命令中使用已经到位的相同的光激活协议，从而促进通过 牙医。此外，甲基丙烯酰胺功能化的硫代乙烷低聚添加剂将被设计为 加入到树脂基质中，目的是提供更均匀的网络 由于折射率的提高与无机填料匹配，因此具有更高的韧性以及更高的固化深度。 提出了三个目标：1)合成甲基丙烯酰胺叔胺单体并对其稳定性进行筛选 对酶/水解的挑战，以及聚合动力学和弯曲性能。材料能够 REACH设定的目标将被配制成复合材料，并在 生理上相关的环境。修复的标本将在含有形成龋齿的房间中循环使用。 细菌，模拟口腔条件。牙齿/修复体界面，以及机械 复合材料本身的性能，将在疲劳循环后进行评估。2)硫代低聚物物种将 用甲基丙烯酰胺系在它们的骨架上合成。硫醇和异氰酸酯的起始原料将 允许控制主干灵活性。基于硫醇烯和氨基甲酸乙酯的模拟低聚物将被用作 控制，使我们能够探索硫脲增韧的机制。弯曲时的机械性能， 聚合收缩、转化率和反应动力学将作为筛选工具，以确定 在减少收缩和增加收缩之间提供最佳折衷的齐聚物 转化率/机械性能(尤其是韧性)。由于它们固有的较高折射率， 硫代乙烷低聚物将改善材料的透光性，并增加固化深度。3) 将合成含醛官能团的甲基丙烯酰胺粘结材料以增强牙本质 通过交联胶原蛋白。结合强度和酶谱图将被用来表征 界面，以及胶原交联剂和蛋白水解性。这个项目的预期结果是 大大减少有机基质的降解和收缩，同时提高转化率和 机械性能，最终克服了目前直接聚合物修复剂的主要缺点。

Abstract The increasing demand for esthetic dental restorations, both by patients and dentists, has stimulated the improvement of resin composites. Currently these materials are used in the vast majority of direct, chair-side restorations delivered each year. However, hydrolysis and enzymatic attack, together with polymerization shrinkage, pose a challenge to the bonded interface between the tooth and the restoration, which reduces the life-time and reliability of the restorations. This study proposes to synthesize novel tertiary methacrylamide monomers to be used as the organic matrix of dental composites and adhesives, completely departing from the conventional methacrylate chemistry used by nearly all current materials. This monomer system is ideal for this application because it is resistant to hydrolysis and enzymatic attack, and also can be polymerized in situ on command using the same photoactivation protocols already in place, thus facilitating its acceptance by dentists. In addition, methacrylamide-functionalized thiourethane oligomeric additives will be designed to be incorporated into the resin matrix with the objective of providing more homogeneous networks with enhanced toughness, as well as enhanced depth of cure due to improved refractive index match with the inorganic fillers. Three aims are proposed: 1) Tertiary methacrylamide monomers will be synthesized and screened for stability to enzymatic/hydrolytic challenges, as well as polymerization kinetics and flexure properties. Materials able to reach established targets will be formulated into composites and evaluated for long-term stability in a physiologically relevant environment. Restored specimens will be cycled in chambers containing caries-forming bacteria, simulating conditions of the oral cavity. The tooth/restoration interface, as well as the mechanical properties of the composite itself, will be assessed after fatigue cycling. 2) Thiourethane oligomeric species will be synthesized with methacrylamides tethered to their backbones. Thiol and isocyanate starting materials will allow control of backbone flexibilities. Analog oligomers based on thiol-enes and urethanes will be used as controls, allowin us to probe the mechanism of toughening by thiourethanes. Mechanical properties in flexure, polymerization shrinkage, degree of conversion and reaction kinetics will be used as screening tools to identify the oligomer providing the best compromise between decreased shrinkage and increased conversion/mechanical properties (especially toughness). Due to their inherently higher refractive index, thiourethane oligomers will improve light transmission through the material and increase depth of cure. 3) Methacrylamide adhesive materials will be synthesized with aldehyde functionalities to reinforce dentinal collagen through crosslinking. Bond strength and zymography will be used to characterize the quality of the interface, as well as collagen crosslinking and proteolytic activity. The expected outcome of this project is to substantially reduce the organic matrix degradation and shrinkage, while increasing conversion and mechanical properties, ultimately overcoming the major drawbacks of current direct polymeric restoratives.