Novel Methacrylate-Thiol-Ene Composites for Dental Restorative Materials

用于牙科修复材料的新型甲基丙烯酸酯-硫醇-烯复合材料

• 批准号: 8780413
• 负责人: NEIL B CRAMER
• 金额: $ 15万
• 依托单位: COLORADO PHOTOPOLYMER SOLUTIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780413
• 关键词: Acrylates; Adhesions; Adhesives; Area; Biocompatible Materials; Clinical; Collaborations; Colorado; Composite Resins; Conversion disorder; Coupled; Coupling; Dental; Dental Materials; Development; Drug Formulations; Elements; Failure; Fatigue; Filler; Funding; Glass; Goals; Grant; Growth; Health; Individual; Knowledge; Lead; Legal patent; Licensing; Life; Longevity; Mechanical Stress; Mechanics; Methacrylates; Methodology; Nature; Optics; Orthodontic; Oxygen; Peer Review; Performance; Phase; Plant Resins; Polymers; Positioning Attribute; Prevalence; Procedures; Property; Publications; Qualifying; Reaction; Refractive Indices; Reliance; Resistance; Safety; Sampling; Services; Small Business Innovation Research Grant; Smiling; Solutions; Speed; Stress; Sulfhydryl Compounds; System; Technology; Testing; Time; Tooth structure; Toxic effect; United States National Institutes of Health; Universities; Urethane; Water; Work; base; biomaterial compatibility; bisphenol A; commercialization; composite restoration; design; experience; forging; improved; innovation; mechanical behavior; medical specialties; monomer; novel; polymerization; premature; restoration; restorative dentistry; restorative material; restorative resins; triethylene glycol dimethacrylate; uptake

DESCRIPTION (provided by applicant): Novel Methacrylate-Thiol-Ene Composites for Dental Restorative Materials. As the demand for aesthetically pleasing restorative materials has increased, so has the desire and demand for improved performance. Despite their increasing prevalence, the resin phase of these materials has remained largely unaltered since Bowen first proposed the materials nearly 50 years ago. Presently, composites suffer from shrinkage and stress that arise during polymerization, a subsequent lack of appropriate mechanical properties of the resin material, and low depth of cure for polymerization. The composites also contain in their core monomer the substitutent bisphenol-A, which is associated with ever increasingly significant regulatory and health concerns. Following polymerization, the composites also contain significant fractions of unreacted monomer that results in the critical presence of extractables that coupled with moisture uptake by the sample can lead to degradation. The result is often secondary cavities and premature failure where composites average lifetime is less than 8 years. Classically, the limitations of these materials have involved a trade-off between the mechanical behavior, the stress and the extent of reaction/conversion of the material that limits extractables and water sorption. The BisGMA/TEGDMA system has proven to be a local optimum within this overall flawed compromise. Here, we propose a novel methodology that changes the reaction paradigm and allows for improvement in each of these critical areas - lower shrinkage and stress, improved mechanics, higher extent of reaction, improved depth of cure along with the elimination of bisphenol-A, and reduced extractables and degradation. An approach using thiol-ene click reactions and monomers is combined with an improved methacrylate approach to yield dramatic improvements in each of these critical areas. Within the two aims of this work, two distinct elements of the formulation are targeted - development and optimization of the resin phase, and development and optimization of the filler/filler coupling agent combination. While both of these aims can proceed independently and will yield valuable results in and of themselves. The synergistic combination of these approaches will forge an entirely new composite dental restorative with expected improvements in conversion, reduced degradation and improved biocompatibility and public safety, mechanics and service life. Specifically, in the first aim, we seek to incorporate urethane-based methacrylates in place of bisphenol-A based monomers. The increased refractive index of the thiol-ene components enables the use of non-bisphenol-A-based monomers - with corresponding benefits of enhanced material properties. Thus, the increased urethane content will result in both improved material properties and reduced shrinkage stress as compared to utilizing BisGMA or BisEMA as the methacrylate in methacrylate-thiol-ene formulations. Second, we propose to focus on the comprehensive development of an integrated filler system that is improved overall and designed specifically for integration with the methacrylate-thiol- ene resins. Our preliminary results have demonstrated a much greater mechanical property enhancement in composite methacrylate-thiol-ene systems than in the control composite BisGMA/TEGDMA systems. These results indicate that the increased conversion of methacrylate-thiol-ene systems will not only dramatically reduce the amount of extractable monomer but also enhance the interaction between the resin phase and the fillers, leading to enhanced mechanical properties. This same benefit is expected to lead to improved adhesion with the native tooth structure. The proposed aims are predicated on the hypothesis that appropriate materials synthesis and subsequent incorporation of urethane-methacrylate base components, optimization of the formulation composition and polymerization mechanism, and optimally designed and modified fillers will improve dental composites through dramatic reductions in shrinkage stress, improvement in composite mechanical properties, moisture uptake and reduced extractables along with improved toxicity and implementation of BPA-free formulations. Results to date demonstrate improved polymerization rates, volume shrinkage induced stress, mechanical properties, depth of cure, oxygen inhibition, toxicity and final conversion. These results will for dental composite systems with enhanced longevity and improved clinical scope. The methacrylate-thiol-ene technology was developed at the University of Colorado by Drs. Cramer and Bowman with funding from an NIH R01 grant (DE018233 - Development of Novel Thiol-Ene-Methacrylate Composites for Dental Restorative Materials). In total, the prior work supported in this area by the R01 grant, of which the PI for this proposal was a co-PI, resulted in 17 peer reviewed publications and two US patents that have been optioned by Colorado Photopolymer Solutions (CPS). Drs Cramer and Bowman have previous experience developing and commercializing dental restorative materials through their collaboration with Septodont Confi-Dental products. During this collaboration, a novel methacrylate formulation from University of Colorado was licensed by Septodont Confi-Dental Products Division and is available commercially as N'Durance (http://www.septodontusa.com/products/n-durance). This provides us with first-hand knowledge for the testing and procedures necessary to commercialize a dental restorative material as well as a potential partner for Phase III. CPS has significant experience in both dental materials and (meth)acrylate and thiol-ene materials. CPS has recently developed and licensed two orthodontic adhesives (Perfect-A-Smile and Bond Aligner) that are currently commercially available through Reliance Orthodontic Products (www.relianceorthodontics.com). CPS also develops and manufactures a range of (meth)acrylate and thiol-ene based formulations for adhesives, optical materials, and other specialty applications.

描述（由申请人提供）：新型甲基丙烯酸-巯基烯复合材料用于牙科修复材料。随着对美观的修复材料的需求增加，对提高性能的愿望和需求也在增加。尽管这些材料越来越普遍，但自从Bowen在近50年前首次提出这些材料以来，这些材料的树脂相基本上保持不变。目前，复合材料受到聚合过程中产生的收缩和应力的影响，随后树脂材料缺乏适当的机械性能，以及聚合的固化深度低。复合材料的核心单体中还含有取代双酚a，这与日益重要的监管和健康问题有关。聚合后，复合材料还含有大量未反应的单体，这导致可萃取物的存在，再加上样品的水分吸收可能导致降解。结果往往是继发性空洞和过早失效，复合材料的平均寿命小于8年。通常，这些材料的局限性涉及到机械行为、应力和材料的反应/转化程度之间的权衡，这限制了可提取性和吸水性。BisGMA/TEGDMA系统已被证明是这一整体缺陷折衷方案中的局部最优方案。在这里，我们提出了一种新的方法，它改变了反应范式，并允许在每个关键领域进行改进-降低收缩和应力，改进力学，提高反应程度，改善固化深度，同时消除双酚a，减少可提取性和降解性。一种使用巯基键合反应和单体的方法与改进的甲基丙烯酸酯方法相结合，在这些关键领域产生了显着的改进。在这项工作的两个目标中，配方的两个不同元素是有针对性的-树脂相的开发和优化，以及填料/填料偶联剂组合的开发和优化。虽然这两个目标可以独立进行，并将产生有价值的结果。这些方法的协同组合将形成一种全新的复合牙科修复体，在转化、减少降解和改善生物相容性、公共安全、力学和使用寿命方面具有预期的改善。具体地说，在第一个目标中，我们寻求将基于聚氨酯的甲基丙烯酸酯代替基于双酚a的单体。巯基组分的折射率增加，使非双酚基单体的使用成为可能，从而增强了材料性能。因此，与使用BisGMA或BisEMA作为甲基丙烯酸酯-硫醇-烯配方中的甲基丙烯酸酯相比，增加的聚氨酯含量将导致材料性能的改善和收缩应力的降低。其次，我们建议将重点放在综合开发一种综合填料系统上，该系统总体上得到改进，并专门设计用于与甲基丙烯酸甲酯-巯基树脂的集成。