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: 8729441
• 负责人: Jack L. Ferracane
• 金额: $ 47.1万
• 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/8729441
• 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; Drug Formulations; Environment; Enzymes; Esthetics; Failure; Fatigue; Filler; Fracture; Future; General Population; Goals; 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; Simulate; 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; public health relevance; restoration; restorative composite; restorative dentistry; restorative material; screening; silane; 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科修复的需求日益增加，刺激了树脂复合材料的改进。目前，这些材料用于每年绝大多数直接的椅旁清洁。然而，水解和酶的攻击，以及聚合收缩，对牙齿和修复体之间的粘结界面提出了挑战，这降低了修复体的寿命和可靠性。本研究旨在合成新的叔 本发明涉及用于牙科复合材料和粘合剂的有机基质的甲基丙烯酰胺单体，完全脱离几乎所有当前材料所使用的常规甲基丙烯酸酯化学。这种单体体系对于这种应用是理想的，因为它耐腐蚀。 水解和酶攻击，并且还可以使用已经存在的相同的光活化方案根据命令原位聚合，从而促进其被牙医接受。此外，甲基丙烯酰胺官能化的硫代氨基甲酸酯低聚物添加剂将被设计为掺入树脂基质中，目的是提供具有增强的韧性的更均匀的网络，以及由于与无机填料的改进的折射率匹配而增强的固化深度。提出了三个目标：1）将合成叔甲基丙烯酰胺单体，并筛选其对酶/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成复合材料，并在生理相关环境中评估其长期稳定性。恢复的样本将在含有龋齿形成细菌的腔室中循环，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物质将用连接到其主链的甲基丙烯酰胺合成。硫醇和异氰酸酯起始材料将允许控制主链柔性。模拟低聚物的基础上硫醇烯和硫醇将被用作控制，使我们能够探测增韧的机制硫代氨基甲酸酯。弯曲、聚合收缩、转化度和反应动力学方面的机械性能将用作筛选工具，以鉴定在降低的收缩和增加的转化/机械性能（特别是韧性）之间提供最佳折衷的低聚物。由于其固有的较高折射率，硫代氨基甲酸酯低聚物将改善通过材料的光透射率并增加固化深度。3)甲基丙烯酰胺粘接材料将合成醛官能团，通过交联增强牙本质胶原。结合强度和酶谱将用于表征界面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降低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增塑剂的主要缺点。