Amorphous calcium phosphate based dental materials

描述（由申请人提供）：我们对基于无定形磷酸钙（ACP）的牙科材料的研究（授权DE13169；于2000年启动）旨在开发具有中等机械强度、对牙齿结构具有良好粘合性以及保护牙齿免于脱矿甚至再生丢失的牙齿矿物质的实验基托/衬垫和正畸水泥。最近，我们团队开发的基于 ACP/聚合物技术的窝沟封闭剂、冠桥粘固剂和光固化正畸粘合剂已向牙科医师投入商业销售。这项持续提案的重点是用于牙髓用途的 ACP 复合材料的设计和评估。由于树脂系统的设计具有高度聚合转化率（导致有机物质的可浸出物最少）以及 ACP 与生物矿物的化学相似性，因此预计此类复合材料将具有良好的生物相容性。后者的生物活性是由于 ACP 一旦暴露于口腔环境就倾向于转化为热力学稳定的磷灰石。所提议的新材料的生物相容性应该等于（如果不超过）目前使用的牙髓材料的生物相容性，并具有 ACP 的持久防龋能力。主要目标是：[1] 评估配制可流动、低收缩的 ACP 复合材料的可行性，同时最大限度地减少未反应单体和/或降解产物的泄漏；[2] 评估材料提取物通过牙本质屏障的体外扩散并评估其细胞毒性。为了实现这些目标，我们建议：（a）配制化学固化和/或双重固化树脂，能够实现高水平的乙烯基转化，同时对聚合时产生的收缩和/或应力产生最小的不利影响，（b）基于此类树脂与精细分散的ACP填料创建复合材料，（c）对未填充树脂（共聚物）和复合材料进行物理化学评估，（d）确定凝固材料提取物穿过牙本质屏障的运动，以及(e) 评估细胞对共聚物和复合材料的反应。拟议研究的完成预计将提供适合牙髓临床评估的模型材料。除了临床影响之外，这些研究还可能提供新的实验证据，以更好地理解聚合物/填充剂和复合材料/牙齿间相现象以及细胞对这些类型牙科材料的反应。 公共健康相关性：拟议的基于无定形磷酸钙 (ACP) 的牙科材料的研究将：a) 有助于对生物活性、再矿化牙科聚合物材料的复杂结构/性能关系的基本理解，b) 为脱矿/再矿化过程的研究提供模型。本研究的一个应用方面是设计具有生物活性和生物相容性的 ACP 牙髓封闭剂。此外，这项技术还可能产生一种可粘合的再矿化材料，该材料粘附在牙齿结构上并可以减轻根部龋齿。

DESCRIPTION (provided by applicant): Our studies of amorphous calcium phosphate (ACP)-based dental materials (grant DE13169; initiated in the year 2000) were aimed to develop experimental bases/liners and orthodontic cements with moderate mechanical strength, good adhesiveness to tooth structures and pronounced potential to protect teeth from demineralization or even regenerate lost tooth mineral. Recently, a pit and fissure sealant, a crown and bridge cement and a light-cure orthodontic adhesive, all based on ACP/polymer technology developed in our group, have been made commercially available to dental practitioners. This continuing proposal focuses on design and evaluation of ACP composite materials intended for endodontic utility. The expected favorable biocompatibility of such composites is anticipated because of the design of resin systems with a high degree of conversion on polymerization (resulting in minimal leachables of organic species) and the chemical similarity of ACP to biological mineral. The bioactivity of the latter is due to the propensity of ACP to convert to thermodynamically stable apatite once exposed to oral milieu. The biocompatibility of the proposed new materials should be equal to, if not exceeding, the biocompatibility of currently utilized endodontic materials with the added benefit of ACP's long-lasting anti-cariogenic power. The main objectives are: [1] to assess the feasibility of formulating flowable, low-shrinking ACP composites with minimized leakage of unreacted monomers and/or degradation products and [2] to evaluate in vitro diffusion of material extracts through dentin barrier and assess their cytotoxicity. To achieve these goals we propose to: (a) formulate chemical cure and/or dual-cure resin capable of attaining high levels of vinyl conversion with the minimal adverse effect on shrinkage and/or stress developed upon polymerization, (b) create composites based on such resins with finely-dispersed ACP fillers, (c) evaluate physico-chemically both the unfilled resins (copolymers) and composites, (d) determine the movement of extracts of set materials across a dentin barrier, and (e) assess cellular response to copolymers and composites. The completion of the proposed research is expected to provide model material(s) suitable for endodontic clinical evaluation. In addition to the clinical impact, the studies may offer new experimental evidence still needed to better understand the polymer/filler and composite/tooth interphase phenomena as well as the cellular responses to these types of dental materials. Public Health Relevance: The proposed research on amorphous calcium phosphate (ACP)-based dental materials will: a)contribute to the basic understanding of the complex structure/property relationships in bioactive, remineralizing dental polymeric materials, and b) provide a model for the study of the demineralization/remineralization processes. An applicative aspect of this study is the design of an ACP endodontic sealer that would be both bioactive and biocompatible. Additionally, this technology may also lead to a bondable, remineralizing material that adheres to tooth structures and could mitigate root caries.