Regulation and Control of Mineralization in Teeth

描述（由申请人提供）：拟议的研究旨在提高我们对仿生方法如何用于使龋釉质脱矿并适当恢复正常牙釉质结构和性质的理解。我们的工作假设是，可以通过调节矿物离子扩散、晶体生长动力学和晶体取向来实现适当牙齿结构和功能的恢复或再生。研究将由一个工作的数学模型来指导，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，基于使用一种新的化学方法来使体内类似初期龋蚀病变局部化所产生的实验数据。以该模型为基础，将研究牙齿结构再矿化和再生的新型仿生方法。提出的仿生策略是基于我们目前的知识状态，如何矿物沉积和组织的发展中的矿化组织的监管。鉴于龋齿的高患病率，存在对上级目前可用的那些的修复程序的巨大需求。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。一般而言，这些研究考虑了离子扩散和人牙釉质中溶解和沉淀的驱动力的重要性，沿着调节牙釉质矿物晶体生长速率和形状的合成和生物相关分子的作用。具体而言，我们建议：1。探讨新型酸性骨矿化液的作用机制和潜在的体外骨矿化效果; 2.确定由选定的唾液蛋白质和肽稳定的过饱和磷酸钙溶液的机制和再矿化有效性：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有效性，其中再矿化动力学由添加的磷酸酶调节; 4.建立一个体外实验系统，利用显微放射照相、偏光显微镜和X线断层扫描技术研究釉质裂病变的再矿化。确定稳定的无定形磷酸钙（ACP）作为成熟釉质晶体外延生长前体的可能作用，特别关注龋性釉质裂隙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.