Amorphous calcium phosphate based dental materials

描述(由申请人提供)：我们对无定形磷酸钙(ACP)基牙科材料的研究(获得DE13169拨款；于2000年启动)旨在开发机械强度适中、对牙齿结构具有良好粘附性并具有显著保护牙齿免受脱矿甚至再生丢失牙矿物质潜力的实验性基托/衬垫和正畸粘固剂。最近，一种基于我们团队开发的ACP/聚合物技术的窝沟封闭剂、冠桥粘固剂和光固化正畸粘结剂已投入商业使用。这项持续的提案侧重于设计和评估用于根管治疗的ACP复合材料。由于树脂体系的聚合转化率高(导致有机物种的可浸出性最小)以及ACP与生物矿物的化学相似性，此类复合材料预期具有良好的生物相容性。后者的生物活性是由于ACP一旦暴露在口腔环境中就有转化为热力学稳定的磷灰石的倾向。建议的新材料的生物兼容性应等于(如果不是超过)目前使用的牙髓材料的生物兼容性，并增加ACP持久的抗龋齿能力。主要目标是：[1]评估研制流动性好、收缩小、泄漏最少的未反应单体和/或降解产物的ACP复合材料的可行性；[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)配制能够实现高水平的乙烯基转化率的化学固化树脂和/或双固化树脂，同时最大限度地减少聚合时产生的收缩和/或应力的不利影响；(B)以这种树脂为基础，使用细小分散的ACP填料创建复合材料；(C)对未填充的树脂(共聚物)和复合材料进行物理化学评估；(D)确定固化材料的萃取物穿过牙本质屏障的移动；以及(E)评估细胞对共聚物和复合材料的反应。本研究的完成有望为牙髓临床评价提供合适的模型材料(S)。除了临床影响，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的牙科材料的反应。 公共卫生相关性：拟议的基于无定形磷酸钙(ACP)的牙科材料的研究将：a)有助于基本理解生物活性、再矿化牙科聚合物材料中的复杂结构/性质关系，以及b)为研究脱矿/再矿化过程提供模型。这项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根管封闭剂。此外，这项技术还可能导致一种可粘结的、可再矿化的材料，这种材料可以附着在牙齿结构上，并可以减轻根面龋齿。

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.