Tooth decay is prevalent, and secondary caries causes restoration failures, both of which are related to demineralization. There is an urgent need to develop new therapeutic materials with remineralization functions. This article represents the first review on the cutting edge research of poly(amido amine) (PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP). PAMAM was excellent nucleation template, and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization. NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities. PAMAM+NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates, superior acid-neutralization, and ions release. Therefore, the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone. PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions. Besides, the long-term remineralization capability of PAMAM+NACP was established. After prolonged fluid challenge, the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration. Furthermore, the hardness of pre-demineralized dentin was increased back to that of healthy dentin, indicating a complete remineralization. Therefore, the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization, hardness increase, and caries-inhibition capabilities.
Amines ; pharmacology ; Calcium ; Calcium Phosphates ; chemistry ; pharmacology ; Dentin ; chemistry ; Humans ; Nanocomposites ; chemistry ; Nanoparticles ; Tooth Remineralization ; methods

OBJECTIVE: To investigate the effects of novel bioactive glasses (BG) including PSC with high phosphorus component and FBG with fluorine-doped element on promoting remineralization of artificial dentin caries. METHODS: (1) BGs were used in this study as follows: PSC (10.8%P₂O₅-54.2%SiO₂-35.0%CaO, mol.%) were synthesized using phytic acid as the phosphorus precursor through sol-gel method. FBG (6.1%P₂O₅-37.0%SiO₂-53.9%CaO-3.0%CaF₂, mol.%) and 45S5(6.0%P₂O₅-45.0%SiO₂-24.5%CaO-24.5%Na₂O, mol.%) were synthesized by traditional melt method. (2) The above BGs were soaked in simulated body fluid (SBF) for 24 hours. Then X-ray diffraction (XRD) was used to analyze the formation of hydroxyapatite (HA) crystals. (3) Prepared 1 mm thick dentin slices were soaked in 17% ethylene diamine tetraacetic acid (EDTA) for 1 week to demineralize the dentin. Then the dentin slices treated by BG were soaked in SBF for 1 week. Field emission scanning electron micro-scopy (FE-SEM) was used to observe the surface morphology of the dentin slices. (4) Four cavities were prepared to 1 mm depth in each 2 mm thick dentin slice, then were treated with lactic acid for 2 weeks to form the artificial dentin caries. Wax, mineral trioxide aggregate (MTA), PSC and FBG were used to fill four cavities as blank control group, MTA group, PSC group and FBG group respectively. Then the spe-cimens were soaked in SBF for 4 weeks. The changes of depth and density of demineralized dentin were analyzed using Micro-CT before filling and after 2 and 4 weeks filling. RESULTS: (1) PSC and FBG promoted mineral formation on the surfaces of the demineralized dentin. And the speed was faster and crystallinity was higher in PSC group than the FBG and 45S5 groups. (2) The increased mineral density of artificial dentin caries in PSC group were (185.98 ± 55.66) mg/cm³ and (213.64 ± 36.01) mg/cm³ 2 and 4 weeks after filling respectively, which were significantly higher than the control group [(20.38 ± 7.55) mg/cm³, P=0.006; (36.46 ± 10.79) mg/cm³, P=0.001]. At meanwhile, PSC group was also higher than MTA group [(57.29 ± 10.09) mg/cm³; (111.02 ± 22.06) mg/cm³], and it had statistical difference (P=0.015; P=0.006). The depth of remineralized dentin in PSC group were (40.0 ± 16.9) μm and (54.5 ± 17.8) μm 2 and 4 weeks respectively, which were also statistically different from the control group (P =0.010;P=0.001). There were no statistical differences between the control group and MTA group. The above effects of FBG group were between PSC and MTA. CONCLUSION PSC has advantages in the speed, quality and depth of mineral deposition in the demineralized layer of artificial dentin caries. It would be expected to be an ideal material to promote the remineralization of dentin caries.
Dentin ; Silicon Dioxide/pharmacology* ; Dental Caries Susceptibility ; Minerals/pharmacology* ; Phosphorus/pharmacology* ; Tooth Remineralization/methods*

Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility. In the present review, we discuss five pathways toward enamel tissue engineering, (i) enamel synthesis using physico-chemical means, (ii) protein matrix-guided enamel crystal growth, (iii) enamel surface remineralization, (iv) cell-based enamel engineering, and (v) biological enamel regeneration based on de novo induction of tooth morphogenesis. So far, physical synthesis approaches using extreme environmental conditions such as pH, heat and pressure have resulted in the formation of enamel-like crystal assemblies. Biochemical methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals. To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix. Other studies reviewed here have employed amelogenin-derived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces. So far, cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines. Going forward, these limitations may be overcome by new cell culture technologies. Finally, whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration. In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues.
Acid Etching, Dental ; Amelogenin ; Biomimetics ; trends ; Dental Enamel ; metabolism ; Dental Enamel Proteins ; Dentistry ; trends ; Tissue Engineering ; methods ; Tooth Remineralization

To explore the remineralization effect of bioactive glass NovaMin on demineralized dentin specimens, and to study the physical and chemical properties of formed structure at dentin surface.
 Methods: One mm-thickness coronal dentin slices were soaked in ethylene diamine tetraacetic acid (EDTA) for 48 h to prepare the completely demineralized dentin specimens and they were divided into 2 groups: an artificial saliva group (control group) and a NovaMin powder group. The specimens were treated with artificial saliva or NovaMin powder for 2 min (2 times every day), and the interval was 8 hours. Then, the specimens were soaked in the remineralization solution. After 7 days, the scanning electron microscope (SEM), energy dispersive X-ray (EDX), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD) were used to detect dentin morphology, the physical and chemical properties of the formed structure at dentin surface.
 Results: The results of SEM showed that a defined surface layer in the NovaMin powder group could be observed in the SEM imaging at the 7th day, which completely occluded dentinal tubules; the EDX, ATR-FTIR and XRD analysis found that the mineralized layer formed at dentin surface was mainly composed of calcium and phosphate elements, which was similar to the hydroxyapatite-like crystal. However, there were no materials formed at the dentin surface in the control group, and the dentinal tubules were still open.
 Conclusion: NovaMin can remineralize the demineralized dentin specimens and occlude the dentinal tubules in hydroxyapatite-like crystal structure.
Dental Pulp Cavity ; Dentin ; chemistry ; Glass ; Microscopy, Electron, Scanning ; Saliva, Artificial ; Spectroscopy, Fourier Transform Infrared ; Tooth Remineralization ; methods

OBJECTIVETo investigate the adsorption behavior of enamel matrix proteins (EMPs) on the enamel surface and study their effect on biomineralization of enamel using quartz crystal microbalance (QCM) technique.

METHODS AND RESULTSThe EMPs were adsorbed on the enamel surface to form a protein film, which was soaked in simulated body fluid solutions. After 30 days of biomimetic mineralization, the hydroxyapatite nucleation, growth and aggregation occurred with hydroxyapatite crystal formation on the enamel surface.

CONCLUSIONThe EMPs play a key role in regulating enamel mineralization.

Adsorption ; Animals ; Dental Enamel Proteins ; metabolism ; pharmacology ; Humans ; Hydroxyapatites ; analysis ; chemistry ; Quartz ; Rats ; Rats, Sprague-Dawley ; Surface Properties ; Tooth Remineralization ; methods

OBJECTIVETo compare the effect of original and neutral Galla chinensis in promoting the remineralization of initial enamel carious lesions in vitro and to investigate the influence of Galla chinensis with different pH on the promoting effect.

METHODSBovine sound enamel slabs were demineralized to produce initial carious lesion in vitro. Then the lesions were exposed to a pH-cycling regime for 12 days. Each daily cycle included 4 × 1 min application of one of four treatments: distilled and deionized water (DDW), aqueous solutions of NaF, acidic or neutral aqueous solutions of Galla chinensis extract (GCE). Before and after pH-cycling, the surface topography of the enamel slabs was observed by atomic force microscopy (AFM), and the integrated mineral loss and lesion depth of all the specimens were analysed by transverse microradiography.

RESULTSAFM images revealed the surface topographical changes of GCE-treated enamel. The percentage change of integrated mineral loss (ΔIML%) of the samples of NaF group, DDW group, pH 3.8 GCE group and pH 7.0 GCE group was (-38 ± 14)%, (+43 ± 7)%, (-10 ± 4)% and (-11 ± 4)% respectively. The percentage of lesion depth (ΔLD%) of the samples of NaF group, DDW group, pH 3.8 GCE group and pH 7.0 GCE group was (-27.79 ± 3.51)%, (+21.13 ± 2.83)%, (-8.43 ± 3.32)% and (-9.20 ± 3.89)% respectively. There was no significant difference in ΔIML% and ΔLD% between pH 3.8 and pH 7.0 GCE-treated enamel.

CONCLUSIONSThere is no significant difference in enhancement of remineralization of initial enamel carious lesions between the original and neutral Galla chinensis. Different pH Galla chinensis does not have obvious influence on remineralization. It is unnecessary to regulate the pH value of queous solution of Galla chinensis extract which acts as a anti-caries agent.

Animals ; Cariostatic Agents ; pharmacology ; Cattle ; Dental Caries ; drug therapy ; Dental Enamel ; drug effects ; ultrastructure ; Drugs, Chinese Herbal ; pharmacology ; Hydrogen-Ion Concentration ; Microscopy, Atomic Force ; Tooth Remineralization ; methods

OBJECTIVETo evaluate in vivo the remineralization containing trace elements.

METHODSThe volunteers were selected by pre-designed criteria of adopting and eliminating. Caries-like lesions were prepared in the enamel of extracted human premolars with the use of demineralizing solution. Sections of the normal and lesion enamel (approximately 2 mm x 2 mm) were prepared, with the cut surfaces protected by nail varnish. 2 enamel specimens were mounted in a removable appliance. By measuring lesion parameters (area, total and average dye fluorescence) on a tooth with confocal laser scanning microscopy (CLSM), the effect of remineralization was assessed. Specimens were cut and stained with a fluorescent dye (0.1 mmol/L rhodamine B) for 1 h and analyzed using CLSM.

RESULTSCLSM detected significantly greater remineralization (P < 0.05) in the specimens treated with the trace elements fluoride-containing solution and only containing fluoride (P < 0.05), especially more obvious difference was shown upon remineralized solution with trace elements, which means it produced a greater remineralization. CLSM data of remineralized solution with trace elements were showed: delta Z vs. Area = -50.4 +/- 8.1; delta Z vs. TF = -27.8 +/- 3.8; delta Z vs. AF = -91.5 +/- 8.9.

CONCLUSIONSThe ability of remineralization of the new solution is better than that only containing fluoride in in vivo study. It can potentially prevent initiation of caries. This study provides not only the theoretical foundation for clinical application, but also shows a new kind of experimental method in the study of demineralization and remineralization.

Dental Caries ; drug therapy ; metabolism ; Dental Enamel ; drug effects ; metabolism ; Fluorides ; pharmacology ; Humans ; Microscopy, Confocal ; Tooth Remineralization ; methods ; Trace Elements ; pharmacology

AIMThe effect of Galla chinensis on de-/re-mineralization of advanced enamel lesions was investigated by using micro-CT in a prolonged in vitro experiment.

METHODOLOGYBaseline mineral contents of sound enamels were first analyzed. Then lesions were produced in an acidic buffer solution (2.2 m mol x L(-1) Ca(NO3)2, 2.2 mmol x L(-1) KH2PO4, and pH = 4.5) for 21 days, with thrice daily three-minute treatments, divided into four groups: Group A, 4 000 ppm crude aqueous extract of Galla chinensis (GCE); Group B, 4000 ppm gallic acid; Group C, 1000 ppm F aq. (as NaF, positive control); Group D, deionized water (negative control). Next, the blocks were immersed in a remineralization solution (1.5 mmol x L(-1) CaCl2, 0.9 mmol x L(-1) KH2PO4, 0.1 ppm F, and pH = 7.0) for 200 days. Mineral loss (ML) in each region of interest (ROI) and integrated mineral loss (IML) of the lesions were calculated (comparing with baseline mineral content of sound enamel) at different time points.

RESULTSAfter 21 days demineralization, fluoride treatment showed a statistically significant demineralization-inhibiting effect among the four groups, and after 200 days of remineralization, mineral content recovery was ordered (lowest to highest) as A = C < B < D.

CONCLUSIONGCE could slow down the remineralization of enamel in the surface layer and thereby facilitate ion transport into the lesion body. The mechanism of Galla chinensis in enhancing the remineralization of dental caries is different from fluoride.

Animals ; Cariostatic Agents ; therapeutic use ; Cattle ; Dental Enamel ; chemistry ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Gallic Acid ; therapeutic use ; Image Processing, Computer-Assisted ; Materials Testing ; Minerals ; analysis ; Plant Extracts ; therapeutic use ; Sodium Fluoride ; therapeutic use ; Time Factors ; Tooth Demineralization ; prevention & control ; Tooth Remineralization ; methods ; X-Ray Microtomography

To test the efficacy of two calcium phosphate pastes compared to that of fluoride toothpaste on remineralizing artificial caries in situ, this study had a double-blind crossover in situ design, involving three experimental phases of 14 days each, with an 8-day washout period between phases. Nine healthy subjects participated in the study. The subjects wore removable palatal appliances mounted with six human enamel slabs with artificial caries lesions, and in each of the experimental phases, used one of the following methods two times/day: group A, brushing with 1.0 g of Colgate Regular Flavor, followed by applying 0.25 g of Tooth Mousse Plus; group B, brushing with 0.25 g of Clinpro Tooth Crème; and group C, brushing with 1.0 g of Colgate Regular Flavor. After 14 days, the enamel slabs (54 slabs/group) were embedded in resin, sectioned and examined with a polarized-light microscope, and the lesion areas were quantified using Image-Pro Plus. All experimental groups showed a significant reduction in lesion area compared to the initial lesion area (paired t-test, P<0.001). The mean reduction in lesion area of Groups A, B and C were (0.029±0.010), (0.030±0.009) and (0.027±0.009) mm(2), respectively. There were no statistical differences between groups (Kruskal-Wallis test, P>0.05). All three groups remineralized the enamel slab lesions, indicating model sensitivity to fluoride. Given the differences in usage amounts and treated regimens, Clinpro Tooth Crème provided similar benefits to the fluoride toothpaste; however, no additional benefit of Tooth Mousse Plus was observed when used in conjunction with the fluoride toothpaste.
Calcium Phosphates ; therapeutic use ; Cariostatic Agents ; therapeutic use ; Caseins ; therapeutic use ; Cross-Over Studies ; Dental Caries ; prevention & control ; Dental Enamel ; drug effects ; Dentifrices ; therapeutic use ; Double-Blind Method ; Female ; Fluorides ; therapeutic use ; Humans ; Image Processing, Computer-Assisted ; methods ; Male ; Microscopy, Polarization ; Tooth Remineralization ; methods ; Toothbrushing ; methods ; Toothpastes ; therapeutic use ; Treatment Outcome ; Young Adult