Figure 5. The amelogenin assemblies manipulate the arrangement
of prenucleation clusters into organized
mesostructures.[193] Copyright 2020, National
Academy of Science.
Physiological
processes and disease diagnosis
Enamel mineralization
Teeth are biomineralized body tissues exposed to the external
environment, which differs from bones. Enamel is more susceptible to
exogenous damage from bacteria, food debris, etc., causing plaque,
dental caries, periodontitis, and other diseases in the
teeth.[198,210] Meanwhile, the enamel is produced
under the regulation of ameloblasts, which undergo programmed apoptosis
after enamel maturation. If there is faulty signaling by ameloblasts in
the regulation of enamel maturation, it can lead to irreversible
amelogenesis imperfect.[2,152] Therefore, studying
exogenous and endogenous factors that affect the physicochemical
properties of enamel mineralization is an essential basis for
maintaining enamel function (Figure 6 ).
The full-scale Raman imaging (~7 mm in diameter)
covering the cross-sectional area of the laser beam can be realized to
illustrate biomineralization by using a high-power
laser.[211] The laser can be guided to the sample
without passing through the objective lens, which greatly saves the time
of Raman scanning. The full-scale Raman image based on mineral intensity
distribution can be used to recognize and distinguish enamel and dentin,
as well as the normally healthy and carious
enamel.[211] Polarization resolution hyperspectral
stimulated Raman imaging technology can analyze the direction change of
biomolecules in dental caries on the submicron scale. The depolarization
rate of the microscope objective used is ~ 0.005, which
is much smaller than the difference between the depolarization rates of
normal enamel and caries, allowing the marking of
caries.[56] Polarized Raman spectroscopy revealed
that healthy enamel exhibited strong Raman polarization anisotropy,
while all early caries showed low Raman polarization
anisotropy.[212] The Raman spectroscopy generated
by ν1PO43- vibrations was strongly
polarized, while the polarization dependence was weaker in the caries
region. This difference in the degree of polarization anisotropy of
Raman spectra becomes a distinct marker to distinguish early caries from
sound enamel. Meanwhile, Raman spectroscopy has also been used in
combination with other techniques for the synergistic diagnosis of
dental caries, such as optical coherence
tomography.[57]
Pathological enamel damage causes a change in the crystal structure of
hydroxyapatite, and the result is a change in the characteristic peaks
of Raman spectroscopy.[58,199,213,214] Raman
spectroscopy was especially used to analyze the relationship between
Msx2 gene expression in ameloblasts and
enamel.[105] There were differences in enamel
composition after knocking out Msx2 in ameloblasts. Figure 7ashows the Raman images reflecting the phosphate vibration modes
ν1 PO43- and
ν4 PO43- in enamel.
The position of ν4PO43- in enamel after Msx2 knockout is
uneven, which may be due to the disorder of spatial distribution during
mineralization.[105] And it will affect the
content of hydroxyapatite in enamel (Figure 7b ). After
periodontitis treatment, the main structural changes in tooth tissue
occur in the cementum. The main reasons for the structural changes of
cementum are microbial infection, susceptibility, and periodontal pocket
susceptibility. The alteration of the characteristic peaks of Raman
spectra caused by this phenomenon was used by the Timchenko group to
identify the effect of the treatment of
periodontitis.[198] Marco Antonio diagnosed dental
fluorosis by improving the classification
algorithm.[215] It was found that the b-type
carbonate content increased with fluorosis severity. And the specificity
of the PCA-LDA model, i.e., the combination of principal component
analysis with linear discriminant analysis, for different fluorosis
severity groups was higher than 93%, which could be utilized to
effectively distinguish different degrees of
fluorosis.[215]