Nanoscale structure and phase composition of sound and carious enamel

 描述（由申请人提供）：龋齿或蛀牙是牙菌斑生物膜细菌产生有机酸导致牙釉质脱矿与唾液矿化之间不平衡的结果。龋齿具有极高的发病率，根据WHO，全世界60-90%的儿童和近100%的成年人患有龋齿。作为最普遍的慢性疾病，龋齿是一个重要的公共卫生问题，并大大有助于过高的牙科支出-仅在美国每年约1100亿美元。因此，有一个明确的和目前需要创新的龋齿预防，早期检测和微创修复。一个主要的瓶颈是我们缺乏对纳米级釉质龋病因学的了解。这是在表征釉质的结构和化学中遇到的困难的结果，釉质是一种复杂的分级纳米复合材料，在结构和组成上具有显著的异质性。在本文中，我们表明，原子探针层析成像（APT），具有无与伦比的空间分辨率（<0.4 nm）和无偏的化学选择性的化学成像工具，是唯一能够提供所需的分辨率定量结构和成分信息。具体而言，我们发现存在富镁无定形粒间相（AIGP），其也富含碳酸盐和残余有机物。我们进一步表明，这AIGP优先溶解在酸中，并提供了一个短路的扩散路径的氟化物。基于这些初步数据，我们推测富镁的AIGP在釉质脱矿和再矿化以及龋齿病变的发展中起着不可或缺的作用。本申请的主要目的是定量比较原始外釉质和龋性表面下病变的表面区釉质中的AIGP的分布和组成。我们将通过使用APT和相关技术对因正畸原因而拔除的人牙的釉质进行分析来做到这一点。第二个目标是在PI实验室建立一个龋齿病变发展的体内大鼠模型，用于未来的纵向研究。

 DESCRIPTION (provided by applicant): Caries, or tooth decay, is the consequence between an imbalance between demineralization of enamel due to production of organic acids by bacteria of the plaque biofilm, and remineralization from saliva. Caries has an extremely high morbidity, with 60-90% of children and nearly 100% of adults worldwide having had caries, ac- cording to the WHO. As the most prevalent chronic disease, caries is an important public health problem and contributes significantly to the exorbitant dental expenditure - about $110 billion/year in the US alone. There is, therefore, a clear and present need for innovating caries prevention, early detection, and minimally invasive restoration. A major bottleneck is our lack of understanding of the etiology of enamel caries at the nanoscale. This is a consequence of the difficulties encountered in characterizing structure and chemistry of enamel, a complex hierarchical nanocomposite with significant heterogeneity in structure and composition. Herein we show that atom probe tomography (APT), a chemical imaging tool with unrivaled spatial resolution (<0.4 nm) and unbiased chemical selectivity, is uniquely able to deliver quantitative structural and compositional information at the required resolution. Specifically, we discovered the presence magnesium-rich amorphous inter- granular phase (AIGP) that is also enriched in carbonate, and residual organic matter. We further show that this AIGP is preferentially dissolved in acid and provides a short circuit diffusion path for fluoride. Based on this preliminary data, we hypothesize that the Mg-rich AIGP plays an integral role in enamel de- and remineralization and the development of caries lesions. A major goal of this application is to quantitatively compare the distribution and composition of the AIGP in pristine outer enamel and the surface zone enamel of carious sub surface lesions. We will do so by carrying out analyses of enamel on human teeth extracted for orthodontic rea- sons, using both APT and correlative techniques. A second goal is to establish an in vivo rat model for the development of caries lesions in the PI's lab for future longitudinal studies.