Enamel and dentine remineralization by nano-hydroxyapatite toothpastes

Enamel and dentine remineralization by nano-hydroxyapatite toothpastes

Author links open overlay panel

PeterTschoppeaDaniela L.ZandimaPeterMartusbAndrej M.Kielbassaac

Show more


Get rights and content

Under a Creative Commons license

open access



This in vitro study evaluated the effects of nano-hydroxyapatite (n-HAp) toothpastes on remineralization of bovine enamel and dentine subsurface lesions.


Specimens were demineralized, randomly divided into five groups, and exposed to an aqueous remineralizing solution for two and five weeks (37 °C). Brushing procedures were performed with the respective toothpaste/storage solution slurry twice daily (2 × 5 s; total contact time of the slurries 2 × 120 s/d): storage in remineralizing solution only (0); additional brushing with B (20 wt% zinc carbonate nano-hydroxyapatite, ZnCO3/n-HAp); BS (24 wt% ZnCO3/n-HAp); E (0.14 wt% amine fluoride); or A (7 wt% pure n-HAp). Differences in mineral loss (ΔΔZ) before and after storage/treatment were microradiographically evaluated.


Dentine groups 0, B, BS, and A showed significantly higher ΔΔZ values compared to E (p < 0.05; ANOVA). Enamel ΔΔZ values of group A were significantly higher compared to group E (p < 0.05), whilst no significant differences of these groups could be observed compared to 0, B, and BS (p > 0.05).


With the in vitro conditions chosen, toothpastes containing n-HAp revealed higher remineralizing effects compared to amine fluoride toothpastes with bovine dentine, and comparable trends were obtained for enamel.



1. Introduction

The process of de- and remineralization is governed by the degree of saturation of oral fluids (saliva and plaque) with respect to apatite minerals.1 Given an appropriate change in conditions, remineralization may become the predominant process, thus leading to lesion repair.2, 3 To enhance lesion remineralization, increase of calcium or fluoride concentrations in the oral fluids would seem reasonable.4

For this purpose, fluorides have traditionally been used in various formulations, and the concomitant cariostatic mechanisms can be explained by an increased driving force for fluoridated apatites.5 The decline in dental caries experienced in most industrialized countries can be attributed largely to the widespread use of fluorides,6 and this preventive effect is mainly due to the formation of calcium fluoride-like precipitates hampering demineralization, whilst fluoride levels needed for remineralization are assumed to be higher than those to prevent lesion formation.7

Nano-hydroxyapatite (n-HAp) is considered one of the most biocompatible and bioactive materials, and has gained wide acceptance in medicine and dentistry in recent years.8 Whilst former attempts to use hydroxyapatites clinically did not succeed, synthesis of nano-scaled zinc carbonate hydroxyapatite (ZnCO3/n-HAp) yielded a significant progress, and showed considerable affinity to the enamel surface.9 Nano-sized particles have similarity to the apatite crystals of tooth enamel in morphology and crystal structure.10 Recently, a few reports have shown that n-HAp has some potential to repair dental enamel,11, 12, 13, 14, 15 but no information is available for established dentine lesions. To date, it can be summarized that for remineralization of subsurface lesions by n-HAp containing products, different formulations have been developed, and early data have suggested remineralizing properties.8 However, evidence is still incomplete to substantiate claims by manufacturers,16, 17 and, so far, none of these products has been shown to be more effective than fluorides.

Therefore, the aim of the present study was to evaluate the effects of daily treatment with different n-HAp toothpastes on the remineralization of bovine enamel and dentine subsurface lesions stored in a remineralizing solution. An amine fluoride toothpaste was used as a reference for comparative reasons. We hypothesized (H0) that additional brushing with n-HAp or fluoride toothpastes would result in equal remineralizing effects compared to a pure remineralizing solution (positive control). This null hypothesis was tested against the alternative hypothesis of a difference between products.

2. Materials and methods

2.1. Specimen preparation and demineralization

From 35 bovine incisors 70 enamel specimens (6 × 4 × 4 mm3) were prepared from the labial aspects. Dentine specimens (n = 85) derived from the cervical regions (4 × 3 × 4 mm3), and were prepared as described previously.18 One quarter of each specimen’s surface was covered with acid-resistant nail varnish (Jet-Set; Loreal, Karlsruhe, Germany) to serve as sound control. Following earlier studies, enamel lesions were prepared by immersion in a solution (5 l) containing 6 μM methylhydroxydiphosphonate (MHDP), 3 mM calcium chloride dihydrate (CaCl2·2H2O), 3 mM potassium dihydrogen phosphate (KH2PO4), and 50 mM acetic acid (CH3COOH) (Merck, Darmstadt, Germany) at pH 4.95 in an incubator (37 °C; BR 6000; Heraeus Kulzer) for 14 days.19 Dentine lesions were prepared by immersion in a solution containing 0.0476 mM sodium fluoride (NaF), 2.2 mM calcium chloride dihydrate (CaCl2·2H2O), 2.2 mM potassium dihydrogen phosphate (KH2PO4), 50 mM acetic acid (CH3COOH), and 10 mM potassium hydroxide (KOH) (all chemicals from Merck) at pH 5.0 (37 °C) for five days.20 The solutions were not stirred or replaced during the demineralization period. The pH values of the demineralizing solutions were monitored daily (pH-electrode GE 100 BNC connected to pH-meter GMH 3510; Greisinger, Regenstauf, Germany), and slight elevations were corrected with small amounts of hydrochloric acid (HCl) to maintain a constant pH value between 4.94 and 4.96 for enamel as well as 4.99 and 5.01 for dentine during the demineralization period. Standard buffer solutions (Sigma–Aldrich, Steinheim, Germany) with nominal pH values of 4.0 and 7.0, respectively, and with an accuracy of 0.01 units were used to calibrate the pH metre.

2.2. Solution preparation and treatment of the specimens

Subsequently, half of each demineralized surface was covered with nail varnish (control of baseline demineralization) again. Specimens were randomly divided into five groups (enamel n = 14; dentine n = 17), and were separately stored in a remineralizing solution21, 22 for two and five weeks (37 °C). In accordance with EN ISO 11609 (European standards for preparing artificial saliva/toothpaste slurries), the respective toothpaste (Table 1) was diluted in three parts (1:3) of the remineralizing solution to obtain a homogeneous slurry. Test products were commercially available toothpastes with either ZnCO3/n-HAp or n-HAp (all without any fluorides) as active ingredients; a toothpaste containing amine fluorides served as reference group (Table 1). The pH values of the slurries were measured directly after preparation.

Table 1. Treatment products, regimes and specimen grouping.

Treatment products Code Active compound Concentration Treatment pH
(Remineralizing solution) 0 Calcium and phosphate 1.5 mM Only storage no further treatment 7.00

batch no. 928751019

B Zinc carbonate-nano-hydroxyapatite 20 wt% Slurry (ratio 1:3) from toothpaste with the remineralizing storage solution and brushing for 5 s with a total contact time of 120 s twice daily in all groups 7.39

batch no. 90001091_26-01-2010

BS 24 wt% 7.34

batch no. 435909

E Aminefluoride 0.14 wt% 5.24

batch no. 20.10.11

A Nano-hydroxyapatite 7 wt% 6.94


BioRepair and BioRepair Sensitive; Dr. Kurt Wolff, Bielefeld, Germany.


Elmex Kariesschutz; GABA, Lörrach, Germany.


ApaCare; Cumdente, Tübingen, Germany.

Subsequently, specimens were manually brushed by hand with a soft toothbrush (Meridol; GABA, Lörrach, Germany), and with minimum pressure; brushing procedures were carried out in each subgroup twice daily for 5 s each (with an additional contact time with the slurry of 115 s, thus resulting in a total contact time of 120 s). After each brushing treatment, specimens were washed with deionized water (10 s). Every two days the remineralizing solutions were replenished (250 ml per group each time), and pH values were checked. After two weeks, half of the exposed surfaces were nail-varnished to evaluate interim effects (effect after two weeks).

2.3. Transverse microradiography

After in vitro exposure, thin sections (100 μm) were prepared. Following, contact microradiographs of the specimens were obtained by transverse microradiography, and these were evaluated using a dedicated software (TMR for Windows; Inspektor Research System, Amsterdam, The Netherlands) as described previously;23, 24 ethylene glycol (C2H4(OH)2) (99%; Sigma–Aldrich, Munich, Germany) was used to avoid shrinkage of dentine lesions.25 The investigator was blinded with respect to group allocation.

Mineral density profiles were evaluated from which integrated mineral loss (ΔZ) and lesion depth (LD) values were calculated following initial demineralization (ΔZDemin, LDDemin) and after treatment for either two (ΔZEffect 2, LDEffect 2) or five weeks (ΔZEffect 5, LDEffect 5). Each pair of values was corrected by subtracting the respective values for sound enamel (ΔZSound and LDSound) before data analysis. Changes in mineral loss (ΔΔZ2 = ΔZDemin − ΔZEffect 2, ΔΔZ5 = ΔZDemin − ΔZEffect 5) and lesion depth (ΔLD2 = LDDemin − LDEffect 2, ΔLD5 = LDDemin − LDEffect 5) were analyzed for treatment differences. Positive and negative values of ΔΔZ or ΔLD indicated net remineralization and net demineralization, respectively.

2.4. Statistical analyses

Normal distribution of ΔΔZ and ΔLD was tested (Kolmogorov–Smirnov). For overall comparison of solutions one-way ANOVA was applied; pairwise comparisons used Tukey’s post hoc tests. Comparisons of changes in mineral loss and lesion depth before and after storage/treatment were performed by adjusted paired t-test (Bonferroni; correction factor ×5). Level of significance was set at α = 0.05 (two-sided). Statistical analyses were performed using PASW for Windows (version 18.0; SPSS, Chicago, IL).

3. Results

Thirteen enamel and two dentine specimens were lost with preparation procedures. All de- and remineralized specimens developed subsurface lesions consistently revealing a surface layer that was more mineralized than the body of the lesion, and none of the treatment regimens yielded surface erosions. Baseline ΔZDemin and LDDemin values (after demineralization) did not differ significantly between the various groups (p > 0.161; ANOVA). With dentine, specimens of group E revealed a hypermineralized surface layer (with an increased thickness), and subsurface lesions could be found with all groups (Fig. 1). The pH values of the remineralizing solutions remained stable for the experimental period.


Fig. 1. Mean mineral density profiles (enamel and dentine) after two and five weeks with or without additional toothpaste treatment (0 = no further treatment; B = ZnCO3/n-HAp 20 wt%; BS = ZnCO3/n-HAp 24 wt%; E = amine fluoride 0.14 wt%; A = n-HA 7 wt%) compared to baseline. Lesion bodies and surface layers of baseline lesions consistently remineralized; hypermineralization of dentine surface layer occurred with group E, but without any decrease of lesion depths.

Enamel ΔΔZEffect 2 and ΔLDEffect 2 values did not differ significantly between groups (p > 0.705; ANOVA, Tukey; Fig. 2). ΔΔZEffect 5 values of group A were significantly higher compared to group E (p = 0.017), whilst no significant differences of both groups could be observed compared to 0, B, and BS (p > 0.221). Comparable results were evaluated for lesion depths after both periods. With dentine, significantly higher ΔΔZEffect 2 values could be observed for groups 0 and B compared to E (p < 0.05), whilst no differences could be seen compared to BS and A (p > 0.101). Groups 0, B, BS, and A showed significantly higher ΔΔZEffect 5 and ΔLDEffect 2/ΔLDEffect 5 values compared to E (p < 0.05).


Fig. 2. Means and confidence intervals (95%; enamel and dentine) of differences in mineral change (ΔΔZ; vol% × μm) and lesion depth (ΔLD; μm) after two (grey) and five weeks (black) storage/treatment (0 = only storage and no further treatment; B = ZnCO3/n-HAp 20 wt%; BS = ZnCO3/n-HAp 24 wt%; E = amine fluoride 0.14 wt%; A = n-HA 7 wt%). Different letters indicate significant differences between groups within each storage/treatment period (p < 0.05; ANOVA, Tukey post hoc test).

Enamel groups 0, E, and A showed significantly decreased ΔZEffect 2 values compared with baseline demineralization (p < 0.05; adjusted t-test, Table 2); B and A significantly decreased ΔZEffect 5 values (p < 0.05). Comparable LDEffect 2/LDEffect 5 values were observed. All dentine specimens revealed significantly decreased ΔZEffect 2/ΔZEffect 5 values if compared with baseline (p < 0.05). LDEffect 5 values of groups 0, B, BS, and A decreased significantly compared with baseline (p < 0.05), whereas values increased for E (p < 0.05).

Table 2. Means with confidence intervals (CI 95%) of mineral losses (ΔZ; vol% × μm) and lesion depths (LD; μm) of enamel and dentine specimens after in vitro demineralization (ΔZDemin, LDDemin) and storage/treatment for two (ΔZEffect 2, LDEffect 2) and five weeks (ΔZEffect 5, LDEffect 5).

Code Mineral loss (vol% × μm)
ΔZDemin ΔZEffect 2 ΔZEffect 5
Mean CI 95% Mean CI 95% p Mean CI 95% p
0 1288 942;1633 655 420;889 0.015 816 410;1221 1.000
B 1572 1014;2131 1124 705;1543 0.170 905 309;1502 0.015
BS 1848 1236;2460 1407 623;2191 0.075 1333 838;1828 0.070
E 1633 1317;1948 1064 625;1503 0.005 1563 994;2131 1.000
A 2147 1547;2746 1429 817;2042 0.005 1202 737;1666 0.010
Code Lesion depth (μm)
LDDemin LDEffect2 LDEffect5
Mean CI 95% Mean CI 95% p Mean CI 95% p
0 83 67;97 58 45;71 0.030 58 39;78 0.180
B 86 70;102 70 52;88 0.220 59 40;78 0.035
BS 90 75;104 77 57;97 0.085 78 61;95 0.230
E 87 77;97 79 61;96 1.000 99 79;118 0.635
A 102 91;114 82 62;102 0.045 75 61;89 0.005
Code Mineral loss (vol% × μm)
ΔZDemin ΔZEffect2 ΔZEffect5
Mean CI 95% Mean CI 95% p Mean CI 95% p
0 3916 3540;4291 2667 2400;2935 0.0005 2217 1923;2511 0.0005
B 3919 3632;4205 2727 2448;3007 0.0005 1980 1739;2220 0.0005
BS 3708 3539;3878 2818 2579;3056 0.0005 2013 1802;2224 0.0005
E 3888 3605;4172 3145 2876;3413 0.0005 3033 2751;3316 0.0005
A 3870 3533;4207 2724 2465;2983 0.0005 2337 1961;2713 0.0005
Code Lesion depth (μm)
LDDemin LDEffect2 LDEffect5
Mean CI 95% Mean CI 95% p Mean CI 95% p
0 197 180;214 176 162;189 0.015 162 144;180 0.0005
B 191 181;201 176 162;189 0.065 151 140;163 0.0005
BS 185 172;198 168 152;184 0.035 149 140;157 0.0005
E 193 179;206 206 193;219 0.195 210 195;224 0.045
A 199 182;215 173 160;187 0.005 176 153;198 0.010

p-Values of differences between the values after demineralization and storage/treatment for either two or five weeks within each group as analyzed by adjusted paired t-tests (Bonferroni correction factor ×5) are given. Pairs differing significantly are highlighted (grey: demineralization; black: remineralization). Treatment code: 0 = only storage and no further treatment; B = ZnCO3/n-HAp 20 wt%; BS = ZnCO3/n-HAp 24 wt%; E = amine fluoride 0.14 wt%; A = n-HA 7 wt%.

4. Discussion

The present in vitro study mainly showed that the different nano-hydroxyapatite toothpastes exert similar capacities to remineralize enamel and dentine subsurface lesions. Furthermore, the fluoride toothpaste displayed the lowest remineralizing effects on both hard tissues, along with an increase in lesion depths. Thus, the null hypothesis (stating that additional brushing with n-HAp or fluoride toothpastes would not result in significantly different remineralizing effects compared to control) was partially rejected.

Rationales for using bovine enamel and dentine specimens have been discussed previously,26 and this source represents an accepted substitute for human dental hard substances.27, 28, 29 Furthermore, several individual factors could have potential impact on remineralization (e.g., behavioural changes, activity of the lesion, depth of the lesion, diet, stimulation of salivary flow, antibacterial and plaque removal strategies, brushing with fluoride toothpaste),3, 30, 31 and these factors may modulate the natural process of lesion arrest (or repair).

The present set-up used abraded and polished specimens; a recent study reported that the in vitro demineralization pattern of unabraded samples more closely resembles the pattern of a natural white spot lesions. However, the inter-sample variation was greater than with abraded specimens,31 and, therefore, we used abraded specimens for standardization reasons.27 The current brushing procedure was accomplished by brushing the specimens with toothpaste/remineralizing solution slurry for 5 s (with 120 s total contact time of the slurry) twice daily. The specimens were manually brushed without any considerable force by the same operator. Indeed, this should not be considered as a completely standardized procedure (i.e., using a brushing machine), even if slightly differing forces should have averaged during the study period.

Some specimens were lost during preparation for TMR. Main problems were surface losses due to sawing or polishing, and these brittle specimens were not suitable for further investigation. In some cases, thin section preparation could be repeated, but this procedure was limited, due to the small dimensions of the specimens. This problem can be only avoided by using non-destructive techniques (like T-WIM).32 However, due to the surface misalignment in the outer ∼15 μm, this method was not considered useful for the current experimental set-up.

In a clinical setting, toothpaste will be diluted, and this strongly depends on individual salivary secretion;33 with the present experimental set-up, one part of toothpaste was dissolved in three parts (1:3) of remineralizing solution to obtain a homogeneous slurry. A major factor of the de- and remineralization equilibrium of enamel is the ambient pH. For slightly acidic fluoride toothpaste slurries with a pH between 4.5 and 5.1, increased remineralization could be observed compared to higher pH values;34 a pH of 5.24 was evaluated with the fluoride toothpaste (according to the manufacturer, the pH is 4.6 for 10% in water). However, only pH values higher than 5.5 have been assumed to promote lesion arrest and to facilitate remineralization.30 In contrast, pH values of n-HAp toothpastes slurries have not been studied up to now, and it might be speculated that the higher pH values of the n-HAp slurries increased remineralization. Recently, for calcium phosphate based solutions a higher mineral gain could be observed with a pH of 6.5 compared to 5.5.19 Moreover, a (constant) remineralization model was used to evaluate the effects of the different toothpastes (n-HAp or ZnCO3/n-HAp versus fluoride). Whilst pH-cycling experiments (including demineralizing periods) might mimic the clinical dynamics more adequately, remineralization-only models offer the opportunity to effectively monitor caries-preventive regimens on dental hard tissues on a short-time basis, thus simulating a best-case scenario.35 With the present approach, initial screening of the effects of hydroxyapatite was accomplished, thus highlighting the advantages of experimental control, even if the breadth of relevant biological aspects was limited.36 Notwithstanding, the current results provide valuable information on n-HAp containing toothpastes, and are considered a sound basis for further experiments.

Dental enamel comprises by 85–90 vol% of a calcium-deficient carbonate hydroxyapatite, whilst dentine contains considerably lower amounts (∼50 vol%).37 With this in mind, in environments supersaturated with respect to apatites, quantity of dentine remineralization should be higher compared to enamel,38 and this was corroborated by the present results. Thus, the current findings with dentine as substrate seem to indicate a meaningful direction, whilst the observations with enamel lesions are of predominantly confirmative value, but not less momentous.

Treatment of specimens with n-HAp or ZnCO3/n-HAp toothpastes did not show any superior effects, but results were comparable to the pure remineralizing solution. From this outcome, one might speculate that n-HAp had no influence at all. However, it should be considered that the used remineralizing control (Buskes’ solution) represents a solution with a substantial remineralizing potential,21 and, therefore, allegorized a positive control. As a consequence, treatment with n-HAp toothpastes revealed no additionally beneficial effect on remineralization. Therefore, usage of a solution with a lower remineralizing potential24 in combination with n-HAP toothpastes might have resulted in superior effects on mineralization compared to only storage under remineralizing conditions. Future pH cycling studies should elucidate these assumptions and are indicated to verify the observed results.

A direct incorporation of n-HAp or ZnCO3/n-HAp particles into the lesions cannot be deduced from the present microradiographic data; however, from previous studies it is known, that crystal growth can be generated with CO3/n-HAp particles.9, 39 Nonetheless, the present results are hardly comparable, since a control group (i.e., only storage in artificial saliva) was missing in the mentioned papers. With the present set-up, dentine specimens of group B revealed the highest mineral gain of all groups after five weeks. Since the tested n-HAp toothpastes contained various active compounds (zinc carbonate nano-hydroxyapatite versus nano-hydroxyapatite), no direct inference seems derivable from the present data; additionally, from a recent paper, it is known that different n-HAp concentrations (>5%) seem to be of minor importance.12 Consequently, it seems reasonable to assume that the higher pH value of group B slurry favoured remineralization by incorporation of n-HAp particles into the dentine lesions. Moreover, with other products (i.e., CPP–ACP) a reduced fall in plaque pH following an immediate carbohydrate challenge has been reported17 and this should be an interesting focus even for n-HAp toothpastes.

It should be emphasized that the used fluoride toothpaste (containing amine fluorides) is one of the well-known and widely used cariostatic products on the market (with documented remineralizing effects being higher than those of toothpastes containing sodium fluorides or monofluorophosphates),35 and, therefore, has been included for comparative reasons. However, enamel and dentine specimens of group E revealed lower mineral gains compared to all other groups (including the controls). Additionally, dentine specimens treated with E revealed a hypermineralization of the surface layer (with an increased thickness), and it might be surmised that a distinct calcium fluoride-like layer on the specimens’ surfaces should have been established by this regimen.40 Moreover, when preparing the slurry, the degree of saturation with respect to calcium fluoride should have increased, and calcium-fluoride-like precipitates should have been favoured.41 Such precipitates may have blocked any further ion transport into deeper lesion parts by decreasing the pore volume of the surface layer and obstructing the diffusion pathways,30 and this could have inhibited further remineralization.42 Furthermore, the observed hypermineralization of the surface layer was accompanied by an increase in lesion depth. Most likely, the low pH (prevailing during brushing with the slurry of group E) caused a redistribution of calcium and phosphates, and minerals situated at the bottom of the lesion should have diffused outwards and re-precipitated at the surface layer. This would be in accordance with the observation that fluorides can drive demineralization further into enamel by making the surface less soluble.43

Because of the different active toothpaste compounds, the pH of the amine fluoride toothpaste slurry was nearly two units lower compared to the hydroxyapatite toothpastes (5.24 and 6.94–7.34, respectively). Due to the lower pH, surface layer mineralization should have increased compared to a higher pH.44 Groups treated with hydroxyapatite toothpaste revealed remineralized subsurface lesions compared to baseline, but without any hypermineralization. The used nano-sized particles (20 nm in size, with granular dimensions up to 100–150 nm)9 as well as the calcium arising from storage solution should have followed a concentration gradient (with the solution higher than the subsurface lesion), thus leading to a remineralizing effect in deeper lesion parts.38

5. Conclusions

The prevention of tooth decay and the treatment of lesions are ongoing challenges in dentistry, and nanotechnology has been claimed as one of the most revolutionary approaches in this field. Notwithstanding, at the moment, the applied and marketable dental products have been studied rarely.8 Interestingly enough, within the limitations of the present in vitro set-up, the different nano-hydroxyapatite toothpastes revealed similar remineralizing capacities with enamel and dentine lesions. For dentine, even higher remineralization effects could be achieved with n-HAp or ZnCO3/n-HAp toothpastes compared to the amine fluoride dentifrice. From the present outcome, we therefore speculate that nano-hydroxyapatite in dental products might help to promote remineralization. However, it is pertinent to note, that this experimental study did not take into account all oral factors; in particular, the complexity of any tooth–pellicle–plaque–saliva interface was not simulated. Hence, the current findings should be confirmed in future in vitro pH-cycling studies and clinical settings.

Declaration of interests

The authors declare that they have no conflict of interest.


The authors are indebted to Mrs. Annette Steinke and Mr. Rainer Toll (Dept. of Operative Dentistry and Periodontology, CharitéCentrum 3, Berlin, Germany) for their excellent monitoring of the laboratory work. This investigation was supported in parts by Dr. Kurt Wolff GmbH & Co KG (Bielefeld, Germany).



H.C. Margolis, E.C. Moreno

Kinetics of hydroxyapatite dissolution in acetic, lactic, and phosphoric acid solutions

Calcified Tissue International, 50 (1992), pp. 137-143

CrossRefView Record in Scopus


E.I. Pearce, A.J. Moore

Remineralization of softened bovine enamel following treatment of overlying plaque with a mineral-enriching solution

Journal of Dental Research, 64 (1985), pp. 416-421

CrossRefView Record in Scopus


A.M. Kielbassa, J. Müller, C.R. Gernhardt

Closing the gap between oral hygiene and minimally invasive dentistry: a review on the resin infiltration technique of incipient (proximal) enamel lesions

Quintessence International, 40 (2009), pp. 663-681

View Record in Scopus


J.D. Featherstone

Remineralization, the natural caries repair process – the need for new approaches

Advances in Dental Research, 21 (2009), pp. 4-7

CrossRefView Record in Scopus


H.C. Margolis, K. Varughese, E.C. Moreno

Effect of fluoride on crystal growth of calcium apatites in the presence of a salivary inhibitor

Calcified Tissue International, 34 (1982), pp. 33-40

View Record in Scopus


E. Brambilla

Fluoride – is it capable of fighting old and new dental diseases? An overview of existing fluoride compounds and their clinical applications

Caries Research, 35 (2001), pp. 6-9

CrossRefView Record in Scopus


C. González-Cabezas

The chemistry of caries: remineralization and demineralization events with direct clinical relevance

Dental Clinics of North America, 54 (2010), pp. 469-478

ArticleDownload PDFView Record in Scopus


M. Hannig, C. Hannig

Nanomaterials in preventive dentistry

Nature Nanotechnology, 5 (2010), pp. 565-569

CrossRefView Record in Scopus


N. Roveri, E. Battistella, C.L. Bianchi, I. Foltran, E. Foresti, M. Iafisco, et al.

Surface enamel remineralization: biomimetic apatite nanocrystals and fluoride ions different effects

Journal of Nanomaterials (2009), 10.1155/2009/746383


J. Vandiver, D. Dean, N. Patel, W. Bonfield, C. Ortiz

Nanoscale variation in surface charge of synthetic hydroxyapatite detected by chemically and spatially specific high-resolution force spectroscopy

Biomaterials, 26 (2005), pp. 271-283

ArticleDownload PDFView Record in Scopus


S. Huang, S. Gao, L. Cheng, H. Yu

Combined effects of nano-hydroxyapatite and Galla chinensis on remineralisation of initial enamel lesion in vitro

Journal of Dentistry, 38 (2010), pp. 811-819

ArticleDownload PDFView Record in Scopus


S.B. Huang, S.S. Gao, H.Y. Yu

Effect of nano-hydroxyapatite concentration on remineralization of initial enamel lesion in vitro

Biomedical Materials, 4 (2009), p. 034104



M.Y. Kim, H.K. Kwon, C.H. Choi, B.I. Kim

Combined effects of nano-hydroxyapatite and NaF on remineralization of early caries lesion

Key Engineering Materials, 330–332 (2007), pp. 1347-1350

CrossRefView Record in Scopus


G. Orsini, M. Procaccini, L. Manzoli, F. Giuliodori, A. Lorenzini, A. Putignano

A double-blind randomized-controlled trial comparing the desensitizing efficacy of a new dentifrice containing carbonate/hydroxyapatite nanocrystals and a sodium fluoride/potassium nitrate dentifrice

Journal of Clinical Periodontology, 37 (2010), pp. 510-517

CrossRefView Record in Scopus


K. Yamagishi, K. Onuma, T. Suzuki, F. Okada, J. Tagami, M. Otsuki, et al.

Materials chemistry: a synthetic enamel for rapid tooth repair

Nature, 433 (2005), p. 819

CrossRefView Record in Scopus


O.A. Adebayo, M.F. Burrow, M.J. Tyas

An SEM evaluation of conditioned and bonded enamel following carbamide peroxide bleaching and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) treatment

Journal of Dentistry, 37 (2009), pp. 297-306

ArticleDownload PDFView Record in Scopus


P.C. Caruana, S.A. Mulaify, R. Moazzez, D. Bartlett

The effect of casein and calcium containing paste on plaque pH following a subsequent carbohydrate challenge

Journal of Dentistry, 37 (2009), pp. 522-526

ArticleDownload PDFView Record in Scopus


P. Tschoppe, H. Meyer-Lueckel, R. Toll, A.M. Kielbassa

In vitro analysis of a new saliva substitute (Saliva natura) on enamel and dentin

Laryngo-Rhino-Otologie, 86 (2007), pp. 723-727

CrossRefView Record in Scopus


H. Meyer-Lueckel, A.J. Chatzidakis, A.M. Kielbassa

Effect of various calcium/phosphates ratios of carboxymethylcellulose-based saliva substitutes on mineral loss of bovine enamel in vitro

Journal of Dentistry, 35 (2007), pp. 851-857

ArticleDownload PDFView Record in Scopus


P. Tschoppe, H. Meyer-Lueckel, A.M. Kielbassa

Effect of carboxymethylcellulose-based saliva substitutes on predemineralised dentin evaluated by microradiography

Archives of Oral Biology, 53 (2008), pp. 250-256

ArticleDownload PDFView Record in Scopus


J.A. Buskes, J. Christoffersen, J. Arends

Lesion formation and lesion remineralization in enamel under constant composition conditions a new technique with application

Caries Research, 19 (1985), pp. 490-496

CrossRefView Record in Scopus


P. Tschoppe, K. Neumann, J. Mueller, A.M. Kielbassa

Effect of fluoridated bleaching gels on the remineralization of predemineralized bovine enamel in vitro

Journal of Dentistry, 37 (2009), pp. 156-162

ArticleDownload PDFView Record in Scopus


H. Meyer-Lueckel, P. Tschoppe, A.M. Kielbassa

Linseed based saliva substitutes and their effect on mineral dissolution of predemineralized bovine dentin in vitro

Journal of Dentistry, 34 (2006), pp. 751-756

ArticleDownload PDFView Record in Scopus


P. Tschoppe, A.M. Kielbassa

Remineralization of bovine enamel subsurface lesions: effects of different calcium-phosphate saturations in buffered aqueous solutions

Quintessence International, 42 (2011), pp. 501-514

View Record in Scopus


A.M. Kielbassa

In situ induced demineralization in irradiated and non-irradiated human dentin

European Journal of Oral Sciences, 108 (2000), pp. 214-221

View Record in Scopus


R.J. Lynch

Model parameters and their influence on the outcome of in vitro demineralisation and remineralisation studies

(1st ed.)R.M. Duckworth (Ed.), The Teeth and Their Environment, Basel: Karger (2006)

p. 65–85


A.M. Kielbassa, E. Hellwig, H. Meyer-Lueckel

Effects of irradiation on in situ remineralization of human and bovine enamel demineralized in vitro

Caries Research, 40 (2006), pp. 130-135

CrossRefView Record in Scopus


A.M. Kielbassa, S.P. Shohadai, J. Schulte-Monting

Effect of saliva substitutes on mineral content of demineralized and sound dental enamel

Supportive Care in Cancer, 9 (2001), pp. 40-47

CrossRefView Record in Scopus


P. Tschoppe, A.M. Kielbassa, H. Meyer-Lueckel

Evaluation of the remineralizing capacities of modified saliva substitutes in vitro

Archives of Oral Biology, 54 (2009), pp. 810-816

ArticleDownload PDFView Record in Scopus


M.C. Peters

Strategies for noninvasive demineralized tissue repair

Dental Clinics of North America, 54 (2010), pp. 507-525

ArticleDownload PDFView Record in Scopus


J. Xue, W. Li, M.V. Swain

In vitro demineralization of human enamel natural and abraded surfaces: a micromechanical and SEM investigation

Journal of Dentistry, 37 (2009), pp. 264-272

ArticleDownload PDFView Record in Scopus


R.Z. Thomas, J.L. Ruben, J. de Vries, J.J. ten Bosch, M.C. Huysmans

Transversal wavelength-independent microradiography, a method for monitoring caries lesions over time, validated with transversal microradiography

Caries Research, 40 (2006), pp. 281-291

CrossRefView Record in Scopus


S.A. Duke, G.C. Forward

The conditions occurring in vivo when brushing with toothpastes

British Dental Journal, 152 (1982), pp. 52-54

CrossRefView Record in Scopus


W.H. Arnold, A. Haase, J. Hacklaender, Z. Gintner, J. Bánóczy, P. Gaengler

Effect of pH of amine fluoride containing toothpastes on enamel remineralization in vitro

BMC Oral Health, 17 (2007), pp. 7-14



A.M. Kielbassa, P. Tschoppe, E. Hellwig, K.T. Wrbas

Effects of regular and whitening dentifrices on remineralization of bovine enamel in vitro

Quintessence International, 40 (2009), pp. 103-112

View Record in Scopus


D.J. White

Reactivity of fluoride dentifrices with artificial caries. I. Effects on early lesions: F uptake, surface hardening and remineralization

Caries Research, 21 (1987), pp. 126-140

CrossRefView Record in Scopus


M. Goldberg, D. Septier, S. Lécolle, H. Chardin, M.A. Quintana, A.C. Acevedo, et al.

Dental mineralization

International Journal of Developmental Biology, 39 (1995), pp. 93-110

View Record in Scopus


T. Aoba

Solubility properties of human tooth mineral and pathogenesis of dental caries

Oral Diseases, 10 (2004), pp. 249-257

CrossRefView Record in Scopus


N. Roveri, E. Foresti, M. Lelli, I.G. Lesci

Recent advancements in preventing teeth health hazard: the daily use of hydroxyapatite instead of fluoride

Recent Patents on Biomedical Engineering, 2 (2009), pp. 197-215

CrossRefView Record in Scopus


J. Christoffersen, M.R. Christoffersen, W. Kibalczyc, W.G. Perdok

Kinetics of dissolution and growth of calcium fluoride and effects of phosphate

Acta Odontologica Scandinavica, 46 (1988), pp. 325-336

CrossRefView Record in Scopus


M.J. Larsen, S.J. Jensen

Experiments on the initiation of calcium fluoride formation with reference to the solubility of dental enamel and brushite

Archives of Oral Biology, 39 (1994), pp. 23-27

ArticleDownload PDFView Record in Scopus


K. Kawasaki, J. Ruben, H. Tsuda, M.C. Huysmans, O. Takagi

Relationship between mineral distributions in dentine lesions and subsequent remineralization in vitro

Caries Research, 34 (2000), pp. 395-403



J.M. ten Cate, R.A. Exterkate, M.J. Buijs

The relative efficacy of fluoride toothpastes assessed with pH cycling

Caries Research, 40 (2006), pp. 136-141

CrossRefView Record in Scopus


B. Ogaard

CaF2 formation: cariostatic properties and factors of enhancing the effect

Caries Research, 35 (2001), pp. 40-44

CrossRefView Record in Scopus

Copyright © 2011 Elsevier Ltd.

Recommended articles



Citing articles (119)

Article Metrics


  • Exports-Saves:
  • Readers:

Social Media

  • Shares, Likes & Comments:
  • Tweets:


  • Citation Indexes: