Tertiary methacrylamides and thiourethane additives as novel dental composites

作为新型牙科复合材料的叔甲基丙烯酰胺和硫氨酯添加剂

• 批准号: 9120842
• 负责人: Jack L. Ferracane
• 金额: $ 45.71万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9120842
• 关键词: Adhesives; Aldehydes; Bacteria; Behavior; Chemicals; Chemistry; Clinical; Clinical Research; Collagen; Composite Resins; Controlled Study; Conversion disorder; Coupled; Data; Dental; Dental Enamel; Dental caries; Dentin; Dentists; Devices; Disadvantaged; Environment; Enzymes; Esthetics; Failure; Fatigue; Filler; Formulation; Fracture; Future; General Population; Goals; Health; Healthcare; Hybrids; Hydrolysis; In Situ; Isocyanates; Kinetics; Life; Longevity; Mechanical Stress; Mechanics; Methacrylates; Microbial Biofilms; Minerals; Modification; Molecular Weight; Oral; Oral cavity; Outcome; Pathway interactions; Patients; Peptide Hydrolases; Physiological; Plant Resins; Polymers; Property; Protocols documentation; Recurrence; Reducing Agents; Refractive Indices; Resistance; Risk; Rosa; Scheme; Services; Side; Silanes; Solubility; Solvents; Specimen; Spectroscopy, Fourier Transform Infrared; Stress; Structure; Sulfhydryl Compounds; Surface; System; Techniques; Technology; Testing; Time; Tooth structure; Urethane; Variant; Vertebral column; Viscosity; Water; analog; base; composite restoration; cost; crosslink; design; esterase; flexibility; improved; interfacial; light transmission; methacrylamide; monomer; novel; photoactivation; polymeric restoratives; polymerization; polymerization shrinkage; polymerization stress; practical application; restoration; restorative composite; restorative dentistry; restorative material; screening; simulation; tool; tooth surface

DESCRIPTION (provided by applicant): 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 delivere 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, allowing 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.

描述（由申请人提供）：患者和牙医对美学牙齿修复体的需求不断增长，刺激了树脂复合材料的改善。目前，这些材料每年在绝大多数直接的椅子饰面中使用。然而，水解和酶促攻击以及聚合收缩，对牙齿和恢复之间的粘合界面构成了挑战，从而降低了修复的寿命和可靠性。这项研究建议合成新的第三纪 甲基丙烯酰胺单体被用作牙科复合材料和粘合剂的有机基质，完全脱离了几乎所有当前材料使用的常规甲基丙烯酸酯化学。该单体系统是此应用的理想选择 水解和酶促攻击，也可以使用已经制定的相同光活化方案在命令上进行聚合，从而促进牙医的接受。此外，将设计甲基丙烯酰胺官能化的硫烷寡聚添加剂，以掺入树脂矩阵中，目的是为了提供更高的韧性以及增强的固化深度，以及由于改善的折射率与无机填充剂匹配而增加的固化深度。提出了三个目的：1）将合成并筛选三级甲基丙烯酰胺单体，以稳定酶/水解挑战，以及聚合动力学和弯曲特性。能够达到已建立目标的材料将被配制为复合材料，并在生理相关的环境中评估长期稳定性。恢复的样品将循环在含有龋齿细菌的腔室中，模拟口腔的条件。牙齿/修复接口， 以及复合材料本身的机械性能，将在疲劳循环后进行评估。 2）将硫代低聚物物种与甲基丙烯酰胺束缚在骨架上合成。硫醇和异氰酸酯的起始材料将允许控制主链柔韧性。基于硫醇和氨基氨酸的模拟低聚物将用作对照，使我们能够探究硫乙烷的韧性机制。弯曲，聚合收缩，转化程度和反应动力学的机械性能将用作筛选工具，以识别低聚物，从而在减少收缩和增加的转化/机械性能（尤其是韧性）之间提供最佳折衷。由于其固有的折射率较高，硫烷寡聚物将改善通过材料的光传输并增加治愈的深度。 3）甲基丙烯酰胺粘合剂将与醛功能合成，以通过交联加固牙本质胶原蛋白。键强度和Zymography将用于表征界面的质量，以及胶原蛋白交联和蛋白水解活性。该项目的预期结果是要大大减少有机基质降解和收缩，同时增加了转化率和机械性能，最终克服了当前直接聚合物恢复的主要缺点。