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

• 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
• 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

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.

项目总结： 牙本质发育不全(DGI)在全球范围内影响6000人中的1人，导致牙病 变色和牙釉质流失。这种缺失通常需要牙齿修复，但也会导致这些修复 失败。尽管牙釉质磨损有这些负面影响，但牙釉质流失的结构/机械原因是 未知。这是由于缺乏对DGI如何影响DEJ结构和局部力学的知识 属性。我们的目的是了解DEJ结构的变化如何影响DGI牙列中的牙齿折断。 在健康的牙列中，DEJ通过一种抗裂复合体成功地将牙釉质和牙本质连接起来 梯度界面结构。在DGI中，釉质磨损表明DEJ受损。一小部分人 研究表明，DGI既影响也不影响DEJ结构。这种困惑源于困难 在测量DEJ的小规模3D层级结构时。我们建议在一只小鼠身上检查DEJ 我们和其他人展示的DGI(Col1a2oim)模型展示了DGI的关键特征。使用状态- 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 健康的和受DGI影响的DEJ。这些分析将统一到DEJ的3D模型中，用于 未来对DEJ对各种修复治疗和病理力量的反应的调查。我们 假设DGI将在DEJ中引起多尺度的结构变化，这将导致 损害了组织力学，增加了DEJ失败的风险。我们将通过两个目标来检验这一假设： 目标1：确定DGI如何影响DEJ的等级结构 高分辨率的微型计算机断层扫描和组织学将提供 德杰。微米级的结构将通过扫描电子显微镜、断层扫描和拉曼光谱进行评估 光谱学3D测绘。纳米结构将通过透射电子显微镜进行识别 体层摄影术。总而言之，这些将提供必要的组成部分，以建立一个具有凝聚力的健康的结构模型 和受DGI影响的DEJ可用于阐明DEJ的功能。 目标2：使用DGI将机械性能的变化与DEJ的结构相关联 DGI和野生型(WT)门牙的节段将在压缩下进行测试，以确定 宏观力学特性。DDE和SIMPLE变形估计程序将识别微尺度 裂纹形成的区域。跨DEJ拍摄的广角和小角X射线衍射图将提供 测量作为载荷和位置函数的胶原蛋白和矿物质应变。 结构和力学数据将通过数值和分析技术相互通知 开发描述DEJ中结构-功能关系的3D模型。这些将提供具有凝聚力的模型 健康的和受DGI影响的DEJ将作为未来根据负荷预测DEJ功能的工具 适用于错牙合期间的修复治疗和对病理性负荷模式的反应。