Dentin Structure, Demineralization and Remineralization

描述(由申请人提供)：目前保守和微创牙科(MID)的趋势强调逆转和修复活跃的龋齿过程作为恢复患病组织的第一步。牙釉质再矿化是一种公认的现象，有既定的机制，但牙本质再矿化策略还处于早期发展阶段。前一阶段的结果显示，水化的龋齿组织的机械性能得到了实质性的恢复，我们称之为“功能性再矿化”。如果功能性再矿化能够在临床上实现，它将成为MID的关键策略，最终结果是改善口腔保健和降低成本。为了支持这一目标，出现了关于基本生物矿化机制的新知识，并启发了新的方法，实现胶原纤维内(纤维内)和纤维之间(纤维外)的适当再矿化，以改善龋齿牙本质结构的功能再矿化。我们建议继续使用加州大学旧金山分校。目标1)加强聚合物诱导的液体前体(PILP)过程，该过程已经成功矿化了各种胶原基质，并显示出人工龋损的显著功能再矿化。B)通过潜在的增效方法扩展PILP，包括其他多阴离子聚合物和恒定组成方法。C)研究龋齿牙本质带的结构，以确定它们在限制再矿化过程中的作用。D)确定正常牙本质和功能再矿化牙本质的显微结构变异。目的2评价牙本质胶原蛋白矿化的模型系统，包括缺乏关键的非胶原蛋白的小鼠模型，以深入了解胶原支架的矿化机制。目标3a)将目标1的改进和目标2的见解应用于两个天然人类龋病体外模型中的应用，这些模型逐渐走向临床应用。目的4通过使用四点弯曲测试和微型X射线计算机断层扫描，确定了基于AFM的水化组织的纳米压痕测试所表明的功能再矿化也反映了临床相关大小的特性。为了开展这项工作，我们建立了一支由旧金山湾区调查人员组成的才华横溢的团队，这些调查人员来自加州大学旧金山分校、LBNL和SSRL，以及我们的佛罗里达州合作者，他们开发了PILP流程。拟议的研究将建立在我们的进展基础上，并转化对生物矿化机制的新理解，以便我们能够优化牙本质龋齿的再矿化动力学和修复，并朝着临床相关的输送系统迈进。建立功能性再矿化牙本质龋齿的方法，从而恢复水化组织的机械性能，将最大限度地减少传统的修复治疗，最大限度地保护牙齿结构。

DESCRIPTION (provided by applicant): Current trends in conservative and minimally invasive dentistry (MID) emphasize the reversal and repair of the active caries process as a first step to restoring the diseased tissue. Enamel remineralization is an accepted phenomenon with established mechanisms, but dentin remineralization strategies are at an early stage of development. Results from the prior period have shown substantial recovery of the hydrated carious tissues mechanical properties, which we have termed "functional remineralization." If functional remineralization can be clinically achieved, it would become a key strategy in MID with the eventual outcome of improved oral health care and lower costs. In support of this goal, , new knowledge on basic biomineralization mechanisms has emerged, and has inspired new approaches that achieve appropriate remineralization within collagen fibrils (intrafibrillar) and between the fibrils (extrafibrillar) to improve the functional remineralization of carious dentin structures. We propose to continue the UCSF-Univ. of Florida collaboration established in the prior period, which will include: Aim 1 a) enhancing the polymer-induced liquid-precursor (PILP) process that has successfully mineralized a variety of collagen matrices, and shown significant functional remineralization of artificial caries lesions. b) extending PILP by potential synergisti approaches including other polyanionic polymers and constant composition methods. c) studying the structure of carious dentin zones to determine their role in limitations of the remineralization process. d) defining microstructural variations in normal and functionally remineralized dentin. Aim 2 evaluates dentin collagen mineralization in model systems including mouse models that lack critical non-collagenous proteins to gain insight into mineralization mechanisms of the collagen scaffold. Aim 3 a) applies the improvements from Aims 1 and insights from Aim 2 to applications in two in vitro models of natural human caries that progressively move towards clinical application. Aim 4 establishes that functional remineralization as indicated by AFM-based nanoindentation testing of hydrated tissue also reflects properties at clinically relevant sizes by use of 4-point bending tests combined with Micro X- ray Computed Tomography. To carry out this work we have established a talented team of SF Bay area investigators from UCSF, LBNL and SSRL, as well as our Florida collaborators who developed the PILP process. The proposed studies will build on our progress and translate the emerging understanding of mechanisms in biomineralization so that we can optimize remineralization kinetics and restoration of dentin caries and move toward a clinically relevant delivery system. Establishing methods to functionally remineralize dentin caries thereby restoring the mechanical properties of the hydrated tissue will minimize conventional restorative treatment and maximize conservation of tooth structure.