Development of high performance, caries-inhibiting dental nano-materials

说明(申请人提供)：继发性龋齿和修复体折裂是更换现有牙齿修复体的最常见原因。在美国，替代牙科占所有手术工作的70%，每年花费50亿美元。在初步研究中，首次合成了纳米磷酸钙(Ca-PO4)和氟化钙(CaF2)，并将其复合到牙科树脂中。拟议研究的目标是：(1)开发新一代承压、防龋纳米复合材料；(2)确定纳米颗粒尺寸和组成以及美观的玻璃共填充增强效果；(3)设计具有超过电流释放修复剂的防龋力、长期机械耐用性和磨损与当前承压、不释放复合材料相匹配的纳米复合材料；以及(4)建立纳米复合材料的加工方法和结构-性能关系。目的1将验证这样的假设：(I)减小纳米颗粒的尺寸将显著增加释放量，远高于含有传统Ca-PO4颗粒的对照复合材料；(Ii)玻璃增强将提高纳米复合材料的强度、韧性和耐磨性，以匹配商业应力承重、不释放的复合材料，并比目前释放的修复剂好2-3倍。目的2将验证这样的假设：(I)纳米复合材料中氟化物的释放与CaF2纳米颗粒的尺寸成反比，与CaF2的体积分数成正比；(Ii)纳米复合材料的强度和韧性将比树脂修饰的玻璃离子对照组高2-3倍，磨损深度是对照组的1/3。目的3将验证以下假设：(I)抑制龋齿的作用取决于纳米颗粒的大小和组成；(Ii)纳米复合材料具有更高的机械性能，比目前释放的修复剂更能有效地预防龋病。Aim 4将测试假设：(I)对水老化和热循环的机械响应将取决于纳米颗粒的大小和组成；(Ii)纳米复合材料，其钙、PO4和F的释放超过当前释放的修复剂，在经过2年的水老化和热循环后，将具有与商业承压、不释放的复合材料相匹配的力学性能；(Iii)在水老化/热循环之后，纳米复合材料将超过对照的长期离子释放。预期成果是：(1)新一代承压纳米复合材料，释放出高水平的抗龋剂来抑制龋齿；(2)通过克服继发性龋齿和修复失败这两大问题，对牙科医学产生重大影响；(3)新型纳米复合材料加工方法、结构-性能关系和模型，可应用于承应力和控释能力都很重要的牙科和骨组织工程领域。 项目简介：该项目首次利用我们实验室合成的新型纳米颗粒，寻求开发新一代承压、抑制龋齿的纳米复合材料，以克服继发性龋齿，这是更换现有修复体的主要原因。替代牙科占所有手术工作的70%，仅在美国就花费了50亿美元/年。此外，该项目将建立新的纳米复合材料加工方法、结构-性能关系和模型，这将有利于承载和控制释放能力都很重要的牙科和骨组织工程。

DESCRIPTION (provided by applicant): Secondary caries and restoration fracture are the most frequent reasons for replacement of existing tooth restorations. Replacement dentistry accounts for 70% of all operative work and costs $5 billion/year in the US. In preliminary studies, nanoparticles of calcium phosphates (Ca-PO4) and calcium fluoride (CaF2) were synthesized for the first time and incorporated into dental resins. The objectives of the proposed research are to: (1) develop a new generation of stress-bearing, caries-inhibiting nancomposites; (2) determine the effects of nanoparticle sizes and compositions, and esthetic glass co-filler reinforcement; (3) design nanocomposites with tooth caries-inhibition capability exceeding current releasing restoratives, and long-term mechanical durability and wear that match current stress-bearing, non-releasing composite; and (4) establish nanocomposite processing methods and structure-performance relationships. AIM 1 will test the hypotheses that: (i) Decreasing the nanoparticle size will significantly increase the release to be much higher than a control composite containing traditional Ca-PO4 particles; (ii) Glass reinforcement will improve the nanocomposite strength, toughness and wear to match commercial stress-bearing, non-releasing composite, and to be 2-3 fold better than current releasing restoratives. AIM 2 will test the hypotheses that: (i) Fluoride release from nanocomposite is inversely proportional to CaF2 nanoparticle size, and is proportional to CaF2 volume fraction; (ii) Nanocomposites will have strength and toughness 2-3 fold greater than a resin-modified glass ionomer control, and wear depth 1/3 that of the control. AIM 3 will test the hypotheses that: (i) Tooth caries inhibition depends on nanoparticle size and composition; (ii) Nanocomposites, with much higher mechanical properties, can prevent tooth caries much more effectively than current releasing restoratives. AIM 4 will test the hypotheses that: (i) Mechanical response to water-aging and thermal-cycling will depend on nanoparticle size and composition; (ii) Nanocomposites, with Ca, PO4 and F release exceeding current releasing restoratives, will possess mechanical properties that match commercial stress-bearing, non-releasing composite, after 2 years of water-aging and thermal cycling; (iii) After water-aging/thermal cycling, nanocomposites will exceed the long-term ion release of the controls. The expected outcomes are: (1) A new generation of stress-bearing nanocomposites with release of high levels of cavity-fighting agents to inhibit tooth caries; (2) Significant impact on dentistry by overcoming the two major problems: secondary caries, and restoration failure; (3) Novel nanocomposite processing methods, structure-property relationships and models, that can be applied to dental and bone tissue engineering where stress-bearing and controlled-release capabilities are both important. PROJECT NARRATIVE: This project, utilizing novel nanoparticles synthesized in our laboratory for the first time, seeks to develop a new generation of stress-bearing, tooth caries-inhibiting nancomposites to overcome secondary caries, which is the major reason for replacement of existing restorations. Replacement dentistry accounts for 70% of all operative work and costs $5 billion/year in the US alone. Furthermore, this project will establish novel nanocomposite processing methods, structure-property relationships and models, which can benefit dental and bone tissue engineering where load-bearing and controlled-release capabilities are both important.