Dentin Structure, Demineralization and Remineralization

牙本质结构、脱矿和再矿化

• 批准号: 8853852
• 负责人: LAURIE B GOWER
• 金额: $ 49.68万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8853852
• 关键词: Acids; Adult; Age; Apatites; Area; Binding; Biological Models; Carbonates; Child; Clinical; Collaborations; Collagen; Collagen Fibril; Communicable Diseases; Complex; Dental; Dental Enamel; Dental caries; Dentin; Dentistry; Development; Disease; Esthetics; Evaluation; Florida; Fluorides; Goals; Growth; Hardness; Healthcare; Human; Kinetics; Knowledge; Lesion; Liquid substance; Magnesium; Mechanics; Methods; Minerals; Modeling; Molecular; Mus; Oral health; Outcome; Pathway interactions; Polymers; Process; Progress Reports; Property; Proteins; Recovery; Reporting; Research Personnel; Role; Specimen; Staging; Structure; System; Testing; Tissues; Tooth structure; Translating; Variant; Work; X-Ray Computed Tomography; Zinc; base; biomineralization; calcium phosphate; clinical application; clinically relevant; cost; demineralization; improved; in vitro Model; insight; mineralization; minimally invasive; mouse model; nanoindentation; nanomechanical; novel; novel strategies; prototype; remineralization; repaired; restoration; restorative treatment; scaffold; simulation; trend

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.

描述（由申请人提供）：保守和微创牙科（MID）的当前趋势强调活动性龋齿过程的逆转和修复是恢复患病组织的第一步。牙釉质矿化是一种公认的现象，其机制已经确立，但牙本质矿化策略仍处于发展的早期阶段。前期的结果表明，水合龋组织的机械性能基本恢复，我们称之为“功能性再矿化”。“如果功能性口腔修复能够在临床上实现，它将成为MID的一个关键策略，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，并激发了新的方法，这些方法在胶原纤维内（纤维内）和纤维之间（纤维外）实现适当的矿化，以改善龋性牙本质结构的功能性矿化。我们建议继续之前建立的UCSF-佛罗里达大学合作，其中包括：目标1 a）增强聚合物诱导的液体前体（PILP）过程，该过程已成功矿化各种胶原基质，并显示出人工龋齿病变的显著功能性矿化。B）通过包括其它聚阴离子聚合物和恒定组成方法的潜在协同方法来扩展PILP。c）研究龋坏牙本质区的结构以确定它们在再矿化过程的限制中的作用。d）定义正常和功能性矿化牙本质中的微结构变化。目的2评价模型系统中的牙本质胶原矿化，包括缺乏关键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的见解应用于两种逐渐走向临床应用的天然人龋齿体外模型。目的4确定，通过使用4点弯曲测试结合微型X射线计算机断层扫描，由基于AFM的水合组织纳米压痕测试所指示的功能性再矿化也反映了临床相关尺寸的特性。为了开展这项工作，我们已经建立了一个有才华的旧金山湾区调查人员从加州大学旧金山分校，LBNL和SSRL，以及我们的佛罗里达合作者谁开发了PILP过程。拟议的研究将建立在我们的进展和翻译的生物矿化机制的新兴理解，使我们可以优化再矿化动力学和牙本质龋的恢复，并走向临床相关的交付系统。建立功能性地使牙本质龋化从而恢复水合组织的机械性质的方法将最小化常规修复治疗并最大化牙齿结构的保护。