Caries, or tooth decay, results from an imbalance between demineralization of enamel due to production of acids by bacteria of the plaque biofilm, and remineralization from saliva. Caries has an extremely high morbidity, with 60-90% of children and nearly 100% of adults worldwide having had caries, according to the WHO. As the most prevalent chronic disease, caries is an important public health problem and contributes significantly to the exorbitant dental expenditure - about $110 billion/year in the US alone. There is, therefore, a clear and present need for innovating caries prevention, early detection, and minimally invasive restoration. A major bottleneck is our lack of understanding of the etiology of enamel caries at the nanoscale. This is a consequence of the difficulties encountered in characterizing structure and chemistry of enamel, a complex hierarchical nano- composite with significant heterogeneity in structure and composition. Herein we show that atom probe tomography (APT), a chemical imaging tool with unrivaled spatial resolution (<0.2 nm) and unbiased chemical selectivity, is uniquely able to deliver quantitative structural and compositional information at the required resolution. Specifically, we discovered the presence of a Mg-rich amorphous intergranular phase (AIGP) in murine and human enamel and of an Fe-rich AIGP in pigmented rodent enamel. We further show that the Mg-rich, but not the Fe-rich AIGP is preferentially dissolved in acid and provides a short circuit diffusion path for fluoride. Based on this preliminary data, we hypothesize that the AIGPs play an integral role in enamel de- and remineralization and the development of caries lesions. A major goal of this proposal is to quantitatively compare the distribution and composition of the AIGP in pristine outer enamel and the enamel of clinical and artificial caries lesions. We will do so by carrying out analyses on teeth from an in vivo rat model, human teeth extracted for orthodontic reasons, and other model systems, using both APT and correlative techniques.

Public Health Relevance

Tooth decay (caries) is an important public health problem that affects nearly everybody at some point in their life and is associated with great cost to society, yet the mechanisms underlying the development of caries lesions remain poorly understood. Atom probe tomography, a chemical imaging technique with unrivaled spatial resolution and chemical sensitivity, provides unprecedented insight into, and will advance our understanding of the progression of enamel nanostructure and phase composition as caries lesions develop. This knowledge will help 1) clarify the mechanism of de- and remineralization that underlie caries lesion formation; 2) clarify biological strategies to harden enamel against acid corrosion; 3) provide high-resolution information integral to developing early caries detection schemes; 4) aid in the development of minimally invasive caries prevention to supersede current surgical management of tooth decay.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral, Dental and Craniofacial Sciences Study Section (ODCS)
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Wan, Jason
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Northwestern University at Chicago
Engineering (All Types)
Biomed Engr/Col Engr/Engr Sta
United States
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Free, R D; DeRocher, K; Stock, S R et al. (2017) Characterization of enamel caries lesions in rat molars using synchrotron X-ray microtomography. J Synchrotron Radiat 24:1056-1064