Elucidating the compositional, structural and mechanical effects of Dentinogenesis Imperfecta on the Dentin-Enamel Junction

阐明牙本质发育不全对牙本质-牙釉质连接处的成分、结构和机械影响

基本信息

批准号：
10370654
负责人：
Alix Deymier
金额：
$ 16.4万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-11 至 2024-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10370654
关键词：
3-Dimensional Affect COL1A2 gene Clinical Collagen Collection Complex Confusion Crystallization DSPP gene Data Defect Dental Dental Enamel Dental crowns Dentin Dentinogenesis Imperfecta Dentition Exhibits Failure Fracture Future Histology Hypertrophy Image Imaging Device In Situ Incisor Individual Investigation Knowledge Link Malocclusion Measurement Measures Mechanics Minerals Modeling Mutation Oral health Pathologic Patients Pattern Positioning Attribute Raman Spectrum Analysis Reaction Resistance Resolution Risk Role Scanning Electron Microscopy Shapes Stress Structural Models Structure Structure-Activity Relationship Synchrotrons Techniques Testing Tissues Tooth Fractures Tooth structure Transmission Electron Microscopy Treatment Failure Work X ray diffraction analysis cohesion composite restoration histological stains interfacial mechanical properties microCT mineralization mouse model nanoscale programs response restoration restoration placement restorative dentistry restorative treatment stem three-dimensional modeling tomography tool

项目摘要

PROJECT SUMMARY: Dentinogenesis imperfecta (DGI) affects up to 1 in 6000 individuals worldwide resulting in dental discoloration and enamel loss. This loss often requires dental restorations but also causes these restorations to fail. Despite these negative effects of enamel attrition, the structural/mechanical cause of the loss is unknown. This is due to a lack of knowledge of how DGI affects the DEJ structure and local mechanical properties. Our objective is to understand how changes in DEJ structure affect tooth fracture in DGI dentition. In healthy dentition, the DEJ successfully connects enamel and dentin via a crack-resistant complex graded interfacial structure. In DGI, enamel attrition suggests that the DEJ is compromised. A small body of studies suggest that DGI both does and does not affect DEJ structure. This confusion stems from the difficulty in measuring the DEJ’s small-scale 3D hierarchical structures. We propose to examine the DEJ in a mouse model of DGI (Col1a2oim), which we and others have shown exhibits the key features of DGI. Using state-of- the-art multi-scale tools we will obtain macro-, micro-, and nano-scale structural and mechanical details of healthy and DGI-affected DEJs. These analyses will be unified into 3D models of the DEJ that will be used for future investigations of the DEJ’s response to various restoration treatments and pathological forces. We hypothesize that DGI will induce multiscale structural alterations in the DEJ that will cause compromised tissue mechanics and increased risk of DEJ failure. We will test this hypothesis via 2 aims: Aim 1: Determine how DGI affects the hierarchical structure of the DEJ High-resolution micro-computed tomography and histology will provide macroscale structure of the DEJ. Micron-level structure will be evaluated via Scanning Electron Microscopy tomography and Raman spectroscopy 3D mapping. Nanoscale structures will be identified via Transmission Electron Microscopy tomography. Together, these will provide the pieces necessary to build a cohesive structural model of healthy and DGI-affected DEJ that can be used to elucidate DEJ function. Aim 2: Correlate changes in mechanical properties with structure across the DEJ with DGI Segments of DGI and wild-type (WT) incisors will be tested under compression to determine macroscale mechanical properties. DDE and SIMPLE deformation estimation programs will identify microscale regions of crack formation. Wide and Small-angle X-ray diffraction patterns taken across the DEJ will provide measures of the collagen and mineral strain as a function of load and position. Structural and mechanical data will inform each other via numerical and analytical techniques to develop 3D models describing structure-function relationships in the DEJ. These will provide cohesive models of both healthy and DGI-affected DEJs that will serve as future tools to predict DEJ function in terms of loads applied during restoration treatments and reactions to pathological loading patterns during malocclusion.

项目概要：牙本质发育不全 (DGI) 影响全球每 6000 人中就有 1 人患有牙本质发育不全 (DGI) 变色和牙釉质损失通常需要牙齿修复，但也会导致这些修复。尽管牙釉质磨损有这些负面影响，但造成损失的结构/机械原因是。这是由于缺乏对 DGI 如何影响 DEJ 结构和局部力学的了解。我们的目标是了解 DEJ 结构的变化如何影响 DGI 牙列中的牙齿断裂。在健康的牙列中，DEJ 通过抗裂复合物成功连接牙釉质和牙本质在 DGI 中，牙釉质磨损表明 DEJ 的一小部分受到损害。研究表明 DGI 既影响又不影响 DEJ 结构这种混乱源于困难。在测量 DEJ 的小规模 3D 层次结构时，我们建议检查小鼠的 DEJ。我们和其他人已经展示了 DGI 模型 (Col1a2oim)，它展示了使用状态的 DGI 的关键特征。最先进的多尺度工具，我们将获得宏观、微观和纳米尺度的结构和机械细节这些分析将被统一到用于 DEJ 的 3D 模型中。 DEJ 对各种修复治疗和病理力量的反应的未来调查。坚持认为 DGI 将引起 DEJ 的多尺度结构改变，这将导致组织力学受损和 DEJ 失败风险增加我们将通过 2 个目标来检验这一假设：目标 1：确定 DGI 如何影响 DEJ 的层次结构高分辨率微型计算机断层扫描和组织学将提供宏观结构 DEJ 微米级结构将通过扫描电子显微镜断层扫描和拉曼进行评估光谱 3D 绘图将通过透射电子显微镜来识别。总之，这些将提供构建健康的有凝聚力的结构模型所必需的部分。以及受 DGI 影响的 DEJ，可用于阐明 DEJ 功能。目标 2：通过 DGI 将 DEJ 的机械性能变化与结构相关联 DGI 和野生型 (WT) 门牙的节段将在压缩下进行测试，以确定 DDE 和 SIMPLE 变形估计程序将识别微观尺度的机械性能。穿过 DEJ 拍摄的广角和小角 X 射线衍射图将提供裂纹形成区域。测量胶原蛋白和矿物应变随负载和位置的变化。结构和机械数据将通过数值和分析技术相互告知开发描述 DEJ 中结构-功能关系的 3D 模型，这将提供有凝聚力的模型。健康和受 DGI 影响的 DEJ 的数据将作为未来预测 DEJ 负载功能的工具在修复治疗期间应用以及对咬合不正期间的病理负荷模式的反应。