Amorphous calcium phosphate based dental materials

描述（申请人提供）：我们对无定形磷酸钙（ACP）基牙科材料的研究（授权DE 13169; 2000年开始）的目的是开发具有中等机械强度、对牙齿结构具有良好的粘附性和保护牙齿免于脱矿甚至再生丢失的牙齿矿物质的显著潜力的实验性基底/衬垫和正畸粘固剂。最近，一种窝沟封闭剂，一种牙冠和牙桥粘固剂以及一种光固化正牙粘合剂，都是基于我们小组开发的ACP/聚合物技术，已经在商业上可供牙科医生使用。本持续提案的重点是设计和评价ACP复合材料用于牙髓实用程序。这种复合材料的预期良好的生物相容性是预期的，因为树脂系统的设计具有高度的聚合转化率（导致有机物质的最小可降解性）和ACP的化学相似性生物mineral. The后者的生物活性是由于ACP的倾向，一旦暴露于口腔环境中，转化为生物稳定的磷灰石。申报的新材料的生物相容性应等于（如果不超过）目前使用的牙髓材料的生物相容性，并具有ACP持久抗龋能力的额外益处。主要目标是：[1]评估配制可流动、低收缩ACP复合材料的可行性，使未反应单体和/或降解产物的泄漏最小化，[2]评估材料浸提液通过牙本质屏障的体外扩散并评估其细胞毒性。为实现这些目标，我们建议：（a）配制化学固化和/或双重固化树脂，其能够获得高水平的乙烯基转化率，同时对聚合时产生的收缩和/或应力的不利影响最小，（B）产生基于具有细分散的ACP填料的这种树脂的复合材料，（c）对未填充的树脂（共聚物）和复合材料，（d）确定凝固材料的提取物穿过牙质屏障的运动，和（e）评估对共聚物和复合材料的细胞反应。预计完成拟议的研究将提供适用于牙髓临床评价的模型材料。除了临床影响外，这些研究还可能提供新的实验证据，以更好地了解聚合物/填料和复合材料/牙齿界面现象以及细胞对这些类型牙科材料的反应。 公共卫生相关性：对无定形磷酸钙（ACP）基牙科材料的拟议研究将：a）有助于对生物活性、可矿化牙科聚合物材料的复杂结构/性能关系的基本理解，以及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一种既具有生物活性又具有生物相容性的ACP根管充填剂。此外，这项技术还可以产生一种可粘结的、可固化的材料，这种材料粘附在牙齿结构上，可以减轻根龋。

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.