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

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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.