Caries, or tooth decay, is the consequence between an imbalance between demineralization of enamel due to production of organic 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, ac- cording 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 nanocomposite with significant heterogeneity in structure and composition. Herein we show that atom probe tomography (APT), a chemical imaging tool with unrivaled spatial resolution (<0.4 nm) and unbiased chemical selectivity, is uniquely able to deliver quantitative structural and compositional information at the required resolution. Specifically, we discovered the presence magnesium-rich amorphous inter- granular phase (AIGP) that is also enriched in carbonate, and residual organic matter. We further show that this AIGP is preferentially dissolved in acid and provides a short circuit diffusion path for fluoride. Based on this preliminary data, we hypothesize that the Mg-rich AIGP plays an integral role in enamel de- and remineralization and the development of caries lesions. A major goal of this application is to quantitatively compare the distribution and composition of the AIGP in pristine outer enamel and the surface zone enamel of carious sub surface lesions. We will do so by carrying out analyses of enamel on human teeth extracted for orthodontic rea- sons, using both APT and correlative techniques. A second goal is to establish an in vivo rat model for the development of caries lesions in the PI's lab for future longitudinal studies.

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 2) 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE025303-02
Application #
9108376
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
Lopez, Orlando
Project Start
2015-07-10
Project End
2016-12-31
Budget Start
2016-07-01
Budget End
2016-12-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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