Multiscale Modeling of Enamel Dissolution - Summary Caries, or tooth decay, results from an imbalance between demineralization of enamel due to production of acids by the plaque biofilm, and remineralization from saliva. 60-90% of children and nearly 100% of adults worldwide have had caries, according to the WHO. As the most prevalent chronic disease, with more than 3 billion cases of untreated caries in 2013, caries is an important public health problem and contributes to the exorbitant dental expenditure (>$180 billion/year in the US). Thus, there is a clear and present need for innovating caries preven- tion, early detection, and minimally invasive restoration. A major bottleneck is our lack of understanding of the dynamics of the processes that underlie enamel lesion formation. This is a consequence of the difficulties en- countered in characterizing structure and chemistry of enamel. Although it has long been known that minor constituents such as CO32-, Mg2+, Na+, Fe, and F- impact solubility greatly, it has been challenging to determine the distribution of the ions at length scales commensurate with the intricate hierarchical microstructure of enamel. Recent work, has revealed that enamel crystallites are cemented together by an amorphous intergranular film enriched in carbonate, magnesium, and other ions and that individual crystallites have a core-shell structure where all minor substituents are enriched in the core. Concentration gradients due to this structure result in significant residual stresses. Hollowed-out crystallites observed after etching in vitro and in caries lesions indicate that the core-shell structure impacts lesion formation. Based on prior and preliminary data, we therefore hypoth- esize that compositional gradients in enamel crystallites impact the dissolution process during caries lesion for- mation both directly, by virtue of the altered chemical composition, and indirectly, by generating residual stresses. Given the small size of enamel crystallites, computational modeling will provide insights that experiments cannot. We will use high fidelity density functional theory (DFT) and ab initio molecular dynamics (AIMD) to simulate structure and composition at the atomic scale and predict mechanical and thermodynamic properties of enamel crystallites and the amorphous phase. In parallel, we will build a continuum phase-field model (PFM) that will capture a wide range of physical phenomena thought to control enamel dissolution. Parametrizing the PFM with experimental data and DFT/AIMD predictions will enable predicting dissolution processes at a scale from indi- vidual to hundreds of crystallites with physiologically accurate compositions and in realistic arrangements. Ex- tensive experimental validation will ensure that the model not only rigorously captures the relevant physics but also accurate predicts the dynamic dissolution processes that underlie erosive tooth wear and caries lesion development. Together, modeling and experiments will allow dissecting the interplay of compositional, structural, and mechanical properties of enamel that underlie caries lesion formation, and to analyze, understand, and predict the impact of current caries treatments – including a highly synergistic nanomaterial developed by one of the co-Investigators.
