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）：患者和牙医对美观牙齿修复体的需求不断增长，刺激了树脂复合材料的改进。目前，每年绝大多数直接椅旁修复都使用这些材料。然而，水解和酶攻击以及聚合收缩对牙齿和修复体之间的粘合界面构成了挑战，从而降低了修复体的使用寿命和可靠性。本研究提出合成新颖的三级 甲基丙烯酰胺单体用作牙科复合材料和粘合剂的有机基质，完全不同于几乎所有当前材料所使用的传统甲基丙烯酸酯化学。该单体系统非常适合该应用，因为它具有抗 水解和酶促攻击，也可以使用现有的相同光活化方案进行原位聚合，从而促进牙医的接受。此外，甲基丙烯酰胺官能化硫氨酯低聚物添加剂将被设计为掺入树脂基质中，目的是提供更均匀的网络，增强韧性，并由于改善与无机填料的折射率匹配而增强固化深度。提出了三个目标：1）将合成并筛选叔甲基丙烯酰胺单体，以确保其对酶促/水解挑战的稳定性以及聚合动力学和弯曲性能。能够达到既定目标的材料将被配制为复合材料，并评估其在生理相关环境中的长期稳定性。修复后的标本将在含有龋齿形成细菌的室中循环，模拟口腔条件。牙齿/修复体界面， 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) 硫代氨基甲酸酯低聚物将通过连接在其主链上的甲基丙烯酰胺来合成。硫醇和异氰酸酯起始材料将允许控制主链柔性。基于硫醇烯和氨基甲酸酯的类似低聚物将用作对照，使我们能够探索硫代氨基甲酸酯的增韧机制。弯曲机械性能、聚合收缩率、转化率和反应动力学将用作筛选工具来识别低聚物，从而在降低收缩率和提高转化率/机械性能（尤其是韧性）之间提供最佳折衷。由于其固有的较高折射率，硫氨酯低聚物将改善材料的透光率并增加固化深度。 3) 合成具有醛官能团的甲基丙烯酰胺粘合材料，通过交联增强牙本质胶原蛋白。键强度和酶谱将用于表征界面的质量，以及胶原交联和蛋白水解活性。该项目的预期成果是大幅减少有机基质的降解和收缩，同时提高转化率和机械性能，最终克服当前直接聚合物修复剂的主要缺点。