Regulation and Control of Mineralization in Teeth

描述(申请人提供)：拟议的研究旨在提高我们对如何利用仿生方法重新矿化龋齿牙釉质并正确恢复正常牙釉质结构和性能的理解。我们的工作假设是，通过对矿物离子扩散、晶体生长动力学和晶体取向的调节，可以实现牙齿结构和功能的恢复或再生。研究将在一个工作的数学模型的指导下进行，该模型将被开发来描述这些关键事件的动力学和相互关系，该模型基于使用一种新的化学方法在体内重新矿化类早期龋齿病变所产生的实验数据。以此模型为基础，将研究新的仿生方法来重新矿化和再生牙齿结构。提出的仿生策略是基于我们目前的知识状态，即矿物沉积和组织在矿化组织发育过程中是如何受到调节的。鉴于龋齿的高患病率，非常需要比目前可用的修复程序更好的修复程序。这些研究的长期目标是开发新的程序来再生正常的牙齿结构和功能。总体而言，这些研究考虑了离子扩散的重要性，以及人牙釉质中溶解和沉淀的驱动力，以及调节釉质矿物晶体生长速度和形状的合成分子和生物相关分子的作用。具体地说，我们建议：1.确定新型酸性再矿化溶液的体外机制和潜在效果；2.确定由选定的唾液蛋白和多肽稳定的过饱和磷酸钙溶液的机制和再矿化效果；3.确定由焦磷酸盐稳定的新型过饱和磷酸钙溶液的再矿化效果，其中再矿化动力学受添加的磷酸酶调节；4.建立体外系统，利用显微放射照相、偏光显微镜和X射线显微断层扫描技术研究釉质裂隙病变的再矿化；5.确定稳定的无定形磷酸钙(ACP)作为成熟釉质晶体外延生长的前驱体的可能作用，特别关注龋裂组织的再矿化和再生。

DESCRIPTION (provided by applicant): The proposed studies are designed to improve our understanding of how biomimetic approaches can be used to remineralize carious enamel and properly restore normal tooth enamel structure and properties. Our working hypothesis is that the restoration or regeneration of proper tooth structure and function can be achieved through the regulation of mineral ion diffusion, crystal growth kinetics and crystal orientation. Studies will be guided by a working mathematical model that will be developed to describe the dynamics and interrelationships of these key events, based on experimental data generated using a novel chemical approach to remineralize in vivo-like incipient carious lesions. Using this model as a basis, novel biomimetic approaches to remineralize and regenerate tooth structures will be studied. The proposed biomimetic strategies are based on our current state of knowledge of how mineral deposition and organization are regulated in developing mineralized tissues. Given the high prevalence of dental caries, there is a tremendous need for restorative procedures that are superior to those presently available. The long-term goal of these studies is to develop new procedures to regenerate normal tooth structure and function. In general, these studies consider the importance of ion diffusion and driving forces for dissolution and precipitation in human enamel, along with the role of synthetic and biologically relevant molecules that regulate the rate and shape of growing enamel mineral crystals. Specifically, we propose: 1. To determine the mechanism and potential effectiveness of novel acidic remineralizing solutions in vitro; 2. To determine the mechanism and remineralization effectiveness of supersaturated calcium phosphate solutions that are stabilized by selected salivary proteins and peptides; 3.To determine the remineralization effectiveness of novel supersaturated calcium phosphate solutions that are stabilized by pyrophosphate, where remineralization kinetics are regulated by added phosphatases; 4.To develop an in vitro system to study the remineralization of enamel fissure lesions using microradiography, polarized light microscopy and X-ray microtomography; and 5. To determine the possible role of stabilized amorphous calcium phosphate (ACP) as a precursor for the epitaxial growth of mature enamel crystals, with particular attention on the remineralization and regeneration of carious enamel fissure tissue.