ANTIMICROBIAL AND REMINERALIZING COMPOSITES FOR CLASS V RESTORATIONS

摘要 在最近的RFA-DE-16-007中，NIDCR强调有必要对V类修复剂进行新的研究 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- 改良的GIC，目前最常用于这些修复体。RFA呼吁进行跨学科研究， 将解决因老年人口健康状况普遍恶化而引起的具体关切 唾液流出，牙周组织受损。我们小组一直走在聚合物研究的前沿， 以无定形磷酸钙(ACP)为基础的生物活性再矿化牙科材料已有20年的历史。我们有 已成功设计出ACP聚合物材料，可通过持续有效地修复丢失的牙矿物质 钙(Ca)和磷(PO4)离子的释放。这些材料用于基托/衬里、正畸和 牙髓应用。 在这份意见书中，我们建议开发新的抗菌剂(AM)和再矿化ACP复合材料，这将 在物理化学、机械和生物性能上均优于传统的V类修复剂。我们将在此基础上 我们对ACP化学和溶液热力学的理解以及对ACP聚合体系的再矿化。我们 将向ACP复合体添加AM功能，使其成为对抗根面龋病的多价工具。为此， 目的：我们将合成新的AM单体，并对树脂进行微调，以改善聚合收缩和 控制聚合应力，同时获得较高的乙烯转化率，最大限度地减少未反应产物的浸出性 单体和/或降解产物，并增强与牙本质的粘结。总体的工作假设是一个 随之而来的，长期AM和再矿化功能是可以实现的，而不会阻碍关键的物理化学， 复合材料的力学性能和生物性能。这一假设将通过以下具体目标进行检验 (SAS)：SA1-新AM单体的合成和验证；SA2-ACP填料的合成和表征；SA3- 共聚物和复合材料的配方、生物相容性、物理化学和机械评价；SA4-AM 树脂和复合材料的活性，以及复合材料的SA5再矿化效果。拟议的研究将产生一个 推荐用于动物研究和/或临床试验的V类修复体的原型AM ACP复合材料。

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.