ANTIMICROBIAL AND REMINERALIZING COMPOSITES FOR CLASS V RESTORATIONS

摘要 在最近的RFA-DE-16-007中，NIDCR强调需要对V类替代品进行新的研究， 最终目标是开发性能优于玻璃离子水门汀（GIC）和/或树脂的新方法/材料- 修改的GIC，目前最常用于这些澄清。RFA呼吁进行跨学科研究， 将解决老年人口健康普遍恶化所引起的具体关切， 唾液流和牙周受损。我们小组一直处于聚合物研究的前沿， 二十年来，基于无定形磷酸钙（ACP）的生物活性牙科材料的研究一直在进行。我们有 已经成功设计的ACP聚合物材料能够通过持续的 释放钙（Ca）和磷酸盐（PO 4）离子。这些材料预期用于基底/衬里、正畸和 牙髓应用 在本申请中，我们建议开发新的抗菌（AM）和抗菌ACP复合材料， 在物理化学、机械和生物学方面优于传统的V类澄清剂。我们将依靠 我们对ACP化学和溶液热力学的理解以及ACP聚合物体系的再矿化。我们 将AM功能添加到ACP复合材料中，使其成为对抗根龋的多价工具。为此 为了达到这一目的，我们将合成新的AM单体，并对树脂进行微调，以改善聚合收缩率， 控制聚合应力，同时获得高程度的乙烯基转化率，最大限度地减少未反应的 单体和/或降解产物，并增强与牙本质的结合。总体工作假设是， 伴随的，长期的AM和矿化功能是可以实现的，而不妨碍关键的物理化学， 复合材料的力学和生物学性能。这一假设将通过以下具体目标进行检验 (SAs)：SA 1-新AM单体的合成和验证; SA 2-ACP填料的合成和表征; SA 3- 共聚物和复合材料的配方、生物相容性、物理化学和力学评价; SA 4- AM 树脂和复合材料的活性，以及SA 5-复合材料的再矿化功效。这项研究将产生一个 原型AM ACP复合材料，用于V类灭菌，可用于动物研究和/或临床试验中的测试。

Abstract In its recent RFA-DE-16-007, the NIDCR emphasizes a need for new studies on Class V restoratives with the ultimate goal to develop new approaches/materials that would outperform glass ionomer cements (GICs) and/or resin- modified GICs, currently most frequently used for these restorations. The RFA calls for interdisciplinary research that would address the specific concerns stemming from generally deteriorated health of elderly population with reduced salivary flow and compromised periodontium. Our group has been on the fore-front of the research on polymeric, bioactive remineralizing dental materials based on amorphous calcium phosphate (ACP) for two decades. We have already successfully designed ACP polymeric materials capable of efficiently restoring lost tooth mineral via sustained release of calcium (Ca) and phosphate (PO4) ions. These materials were intended for base/lining, orthodontic and endodontic applications. In this submission, we propose to develop new, antimicrobial (AM) and remineralizing ACP composites which will physico-chemically, mechanically and biologically outperform the conventional Class V restoratives. We will build upon our understanding of ACP chemistry and solution thermodynamics as well as remineralizing ACP polymeric systems. We will add the AM functionality to ACP composites to make them a polyvalent tool for combating root caries. For that purpose, we will synthesize new AM monomers and fine-tune the resins to improve the polymerization shrinkage and control polymerization stress while attaining high degrees of vinyl conversion, minimize leachability of the unreacted monomers and/or degradation products and enhance bonding to dentin. The overall working hypothesis is that a concomitant, long-term AM and remineralizing function is attainable without impeding the critical physicochemical, mechanical and biological properties of composites. This hypothesis will be tested through the following Specific Aims (SAs): SA1 - Synthesis and validation of new AM monomers; SA2 - Synthesis and characterization of ACP filler; SA3 - Formulation, biocompatibility, physicochemical and mechanical evaluation of copolymers and composites; SA4 - AM activity of resins and composites, and SA5 - Remineralizing efficacy of composites. The proposed research will yield a prototype AM ACP composite for Class V restorations recommendable for testing in an animal study and/or clinical trial.