The role of amorphous intergranular phases in the development of caries lesions

Project: Research project

Description

Dental caries is the most prevalent infectious disease that afflicts humans and a major public health concern. Caries, simply put, is the destruction of tooth biominerals by chemical dissolution and commonly begins with the demineralization of enamel. Tooth enamel is an acellular tissue with a complex, hierarchical architecture. It is primarily composed of hydroxylapatite (OHAp) crystallites, thousands of which that are bundled into rods that are organized in a 3D weave. Enamel homeostasis is entirely the result of a balance of chemical dissolution by plaque biofilm-derived acids, and re-mineralization from saliva. Minor constituents such as Mg2+ and CO32- ions increase solubility; F- decreases solubility and enhances re-mineralization. However, little is known about the distribution of these impurities at the length scale of individual crystallites, and whether other phases than crys-talline apatite may be involved. From a material science point of view, change of the nano-scale structure and phase composition of enamel, i.e. the microstructural evolution, is tightly linked to the progression of caries.
Our long-term goal is to arrive at a quantitative understanding of this microstructural evolution. Our central hypothesis is that a non-apatitic amorphous intergranular phase (AIGP) between hydroxylapatite crystallites controls the resistance of enamel to dissolution during early caries development. We formulated this hypothesis based on the literature as well as our preliminary data from atom probe tomography (APT), an imaging mass spectrometric technique with unrivaled spatial resolution (<0.4 nm) and chemical sensitivity. APT in combination with X-ray absorption spectroscopy indicates the presence of Mg-substituted amorphous calcium phosphate (Mg-ACP) in murine enamel. Exchange of Mg-ACP for Fe-ACP in pigmented enamel strongly de-creases acid dissolution. Fluoride diffuses rapidly along grain boundaries and co-localizes with Mg-ACP.
A major goal of the proposed research is to determine the extent of microstructural evolution of the Mg-rich AIGP by comparing pristine enamel with enamel in clinical caries lesions. We are prepared to perform this re-search because we pioneered APT imaging of enamel. Furthermore, our team comprises experts with prior experience in imaging enamel lesions, biostatistics, and dental surgery, thus ensuring that our quantitative analysis will account for the heterogeneity of teeth and connect the clinical development of caries to the under-lying principles of materials science, while accomplishing the following specific aims:
Aim 1: Determine the chemical nanostructure of human enamel. Hypothesis: Mg-ACP is present in human enamel as AIGP and is remodeled during the development of white spot enamel lesions (WSEL).
a) Characterize the nanoscale phase composition of pristine smooth surface enamel in human premolars.
b) Compare and contrast nanostructure and phase composition of pristine outer enamel and surface zone enamel in clinical smooth surface WSEL.
Aim 2: Establish an in vivo rat model for subsurface caries lesion formation and determine the chemical nanostructure of rat molar enamel. Hypotheses: Mg-ACP is present as an AIGP in rat enamel; further that the nanostructure and phase composition in the surface zone of caries lesions is significantly different from pristine and sound outer enamel.
a) Compare and contrast the onset and severity of caries in molars of Wistar rats on a cariogenic diet with con-trols, and determine the mineral density profile of caries lesions on rat molars.
b) Chara
StatusActive
Effective start/end date12/1/1511/30/20

Funding

  • National Institute of Dental and Craniofacial Research (5R01DE025702-04)

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Dental Enamel
Nanostructures
Tooth
Dental Caries
Tomography
Durapatite
Solubility
Cariogenic Diet
Chara
X-Ray Absorption Spectroscopy
Biostatistics
Apatites
Acids
Bicuspid