Noriko Hiraishi, DDS PhD

Noriko Hiraishi, DDS PhD

Noriko Hiraishi, DDS, PhD Outline of research
Dental caries is one of the most prevalent diseases, resulting in enamel and dentin destruction. Caries treatment involves the removal of the affected dental tissues and their replacement with artificial restorative materials. An approach of enamel and dentin regeneration has not well established; therefore we have to consider to preserve enamel and dentin if these tissue has potentials to recover the function. My research interest is based on the functional restorative technique to preserve enamel/dentin and restore those defect using the dental therapeutic approach and resin adhesive materials.

Key words
Conservative dentistry
Adhesive dentistry
Remineralization and effect of fluoride
Natural compound agents for dental application
Biocompatible dental materialisms
Mussel-mimetic bio-adhesive polymers
Saliva and calculus analysis

Outline of research

➀ Adhesive dentistry

Hydrophobic interaction with collagen at aliphatic compounds
The protons at the aliphatic region show high STD intensities ranging from 73.9% to 100%.
The methyl group protons, H3, also have a high intensity (92.7%)
The methacrylate group protons have relatively weak intensities of 61.1% and 64.1%.

1. Monomers Interaction to Collagen Studied by Saturation Transfer Difference NMR

The interaction with collagen is the most important, because the deterioration of collagen fibrils within the hybrid layer compromises the long-term stability of dentin bonding. We examined the molecular/atomic level interactions of dental resin monomers with collagen model. MDP (10-Methacryloyloxydecyl dihydrogen phosphate) has a relatively stable interaction with the collagen matrix because of the hydrophobic interactions between the hydrophobic MDP moieties and the collagen surface.

2. The auto-degradation of dentine collagen fibrils is responsible for bond degradation within hybrid layers.


Solutions to prevent dentin bond degradation are:
✓Increasing the functional monomers into dentin substrates
✓Inhibitors of Collagenolytic Enzymes
✓The use of cross-linking agents to stabilize collagen matrix, and/or to alter the activities of MMP and cathepsins
2.1 The effect of chlorhexidine to improve dentin bond durability

We evaluated chlorhexidine release from unfilled non-solvated methacrylate-based resins and the effect of chlorhexidine to improve dentin bond durability.

Dental Materials 2008
2.2 Collagen degradation at the resin-dentin interface deteriorates dentin bond durability. The use of natural cross-linkers might offer a positive approach to stabilize the resin-dentin interface.

The incorporation of hesperidin into the self-etching primer had a positive effect on the immediate μTBS and mechanical properties of the resin-dentin interfaces. The 5% HPN group preserved the morphology of the collagen in the hybrid layer after one-year storage in artificial saliva.


TEM images at 80,000x magnification
The Control (without hesperidine, on the left) showed the area of denatured collagen within the hybrid layer indicated by the arrow symbol. The HPN group (with hesperidine in the primer) showed the well organized collagen bundle within the hybrid layer.

② Remineralization and effect of fluoride

Demineralized dentin
Field Emission Scanning Electron Microscope (x 15,000) 
The role of Collagen matrix is important for remineralization

1.The role of collagen matrix on potential of demineralization.

Dentin is a collagenous mineralized tissue, which contains 70% carbonated apatite, 20% organic
matrix, and 10% water (by weight).

In caries:
Demineralization induces expose the collagen matrix. Degradation of collagen fibrils decrease of mechanical properties of dentine

The remineralization of demineralized dentine:
Not simply to form inorganic mineral-like structure,
But also consider the role of collagen fibrils

Collagen preserved by hesperidin application on dentin (on the left). Mineral loss was mild,
Mineral loss was increased in case of collagen degradation (on the right).

2. The role of collagen matrix on potential of demineralization.

The remineralizing process should be regulated through interactions of mineral crystallites with the collagen matrix. We reported the role of collagen matrix on potential of remineralization and the effect of natural cross-linkers such as hesperidin. Hesperidine preserved collagen and inhibited demineralization, and enhanced remineralization.
3. 44Ca doped pH-cycling study on Dentin Remineralization by Isotope Microscopy

Intrinsic 40Ca (tooth-derived mineral) and extrinsic 44Ca (solution-derived mineral) are distinguished by 44Ca doped pH-cycling.
The isotope image of 40Ca and 44Ca distribution is revealed by a high mass-resolution stigmatic secondary ion mass spectrometry system.
The uptake of 44Ca (tooth-derived mineral) is great in intensity especially in the superficial lesions.
When fluoride is used, 40Ca (tooth-derived mineral) distribution is absent in the surface lesions.

Since the fluoride-treated surface is more acid-resistant than intrinsic dentin, alternative minerals were dissolved from the intact intrinsic lesion in the demineralization cycle.


Secondary ion mass spectrometry (SIMS)
Isotopic compositions of rock particles from asteroid 25143 Itokawa returned by the Hayabusa spacecraft.

The pH-cycling was performed for 14 days using 44Ca (a stable calcium isotope) in remineralization solution and fluoride application.
(a) Transverse Microradiography image
(b),(c), (d) Isotope Microscopy image

③ Natural compound agents for dental application

1. Plant-derived Agents to Preserve Dentin Collagen

The effect of various plant-derived agents (hesperidin, proanthocyanidin, epigallocatechin gallate and genipin) was examined on the stability of dentin collagen matrix to resist collagenase degradation. Demineralized human dentin powder was incubated with 0.02 %, 0.1 % and 0.5 % of each test agent and followed by bacterial collagenase digestion. The use of those natural agents could improve the mechanical properties of collagen and resist enzymatic degradation, leading to functional repair of pathological dentin lesion.

When the demineralize dentin was observed at high vacuum SEM condition, the control (without cross-linker) showed collapse collagen network. Meanwhile, glutaraldehyde, grape seed extract and hesperidin preserved collagen networks.

2. The role of flavonoids to preserve collagen matrix for functional remineralization

Dentin collagen can be modified by some plant-derived flavonoids to improve properties of dentin organic matrix. Hesperidin has a potential of dentin modification for being based on evidence that a treatment with HPN may resist collagenase degradation and arrest demineralization of human dentin. Biophysical and molecular-level information on the interaction of HPN and collagen was investigated.
We have performed circular dichroism spectroscopic analysis, sedimentation velocity measurement by ultracentrifuge and saturation transfer difference measurement (STD) by NMR.




Hesperidin interacts through the aromatic parts with atelocollagen.

GSH: Reduced glutathione
ROS: Radical Oxygen Species
➀ GSH deleterious effects of ROS
② GSH binding to HEMA

3. Application of Non-Protein Thiols (NPSH) on dentin application

H3PO4 intensifies the activity of both pro- and active forms of dentinal matrix metalloproteinase (MMPs) activity

NPSH such as reduced glutathione (GSH) was effective to Inhibit H3PO4-activated dentinal MMPs.
NPSH was comparable to chlorhexidine (a standard dentinal MMP inhibitor)
NPSH Inhibit HEMA toxicity on pulpal-like cells:



4. Phytic Acid: Properties and Potential Applications in Dentistry

Phytic Acid has the potential to be the new root canal chelating agent: Phytic Acid proved to be an effective agent in removing the smear layer and restoring the bond-strength to NaOCl-treated dentin while being biocompatible to osteoblast-like cells.




Major storage form of phosphorus in plant seeds and bran

④ Mussel-mimetic bio-adhesive polymers: the alternative to petroleum adhesives

Adhesion mechanism of our bio-adhesives

We has applied the properties of mussel adhesive in synthetic mimics from plant-derived sources as 3,4-dihydroxycinnamic acid (caffeic acid; DHCA) and 4-hydroxycinnamic acid (p-coumaric acid; 4HCA) to synthesize poly-(DHCA-co-4HCA) by transesterification technique (Polymer Journal, 2011). This novel copolymer was found to show strong adhesive characteristics, which were equivalent to conventional superglues from petroleum resources.

⑤ Saliva and calculus analysis

31P-HetCor

19F- and 31P- Solid-state NMR study on fluoridate apatite in Human Dental Calculus

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Fluoride uptake in calculus was investigated by solid-state NMR(Nuclear Magnetic Resonance). 19F-MAS (Magic Angle Spinning) and 1H-31P CP/MAS (Cross Polarization MAS) was applied. 19F-MAS showed considerable fluoride was detected when compared with human enamel and dentin. The 1H-31P HetCor (Heteronuclear correlation)revealed a variety of 31P signals, including hydroxyapatite, brushite and other calcium phosphate compounds.

Varies Fluorides were detected when compared with human enamel and dentin