Clinical Oral Investigations (2022) 26:4437–4445

https://doi.org/10.1007/s00784-022-04407-y

ORIGINAL ARTICLE

An alkasite restorative material effectively remineralized artificial

interproximal enamel caries in vitro
Thipthida Theerarath1 · Wannakorn Sriarj1 

Received: 15 September 2021 / Accepted: 6 February 2022 / Published online: 21 February 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022

Abstract
Objective  To evaluate the remineralization of artificial interproximal enamel caries (AIEC) adjacent to alkasite, high viscous
glass ionomer cement (HVGIC), and resin composite in class II restorations.
Materials and methods  Human enamel specimens were randomly assigned to 3 groups (n = 22): Filtek™ Z350, EQUIA
­Forte®, and Cention N ­ ®. The baseline hardness was determined using a Knoop microhardness assay. AIEC was formed in
the specimens, and they were placed in contact with the proximal restorative materials then subjected to a 7-day pH cycling.
Microhardness was determined post-artificial caries formation and post-pH cycling. The differences in the percentage of
surface hardness recovery (%SHR) between the groups were compared using the Kruskal–Wallis test. The Dunn’s test was
used for between-group comparisons (p < 0.05). Specimen surface morphology was evaluated using scanning electron micros-
copy (SEM), and the calcium, phosphorus, and fluoride contents were analyzed by energy-dispersive spectroscopy (EDS).
ANOVA with the post hoc Tukey multiple comparison test was used to evaluate the differences between groups (p < 0.05).
Results  The Cention ­N® %SHR was the highest, followed by EQUIA F ­ orte®, and Filtek™ Z350. There was a significant
difference in the %SHR between Cention ­N® and Filtek™ Z350 (p < 0.05). In contrast, there were no significant difference
between Cention N ­ ® and EQUIA F ­ orte®. Significantly increased enamel surface fluoride content was observed in the Cen-
®
tion ­N compared with Filtek™ Z350 specimens (p < 0.05). The SEM image of the Cention N ­ ® specimens demonstrated
the greatest mineral deposition.
Conclusions  Cention ­N® markedly increased the surface hardness and fluoride content of adjacent AIEC compared with
Filtek™ Z350 restorations.
Clinical relevance  Cention ­N® is a promising alternative restorative material to remineralize initial enamel lesions in approxi-
mal adjacent surfaces, especially in high-risk caries patients.

Keywords  Dentistry · Remineralization · Interproximal enamel caries · Surface microhardness · Alkasite

Introduction restorative materials containing fluoride can prevent the

The proximal surfaces of a tooth are the greatest contributors
to the high caries prevalence because these are sites of high
plaque accumulation [1]. Managing an early caries lesion on
a proximal tooth surface provides the opportunity to arrest
or reverse the enamel demineralization and does not require
a restoration [2]. Fluoride ions enhance enamel lesion rem-
ineralization and inhibit demineralization [3]. Furthermore,
* Wannakorn Sriarj
wannakorn.s@chula.ac.th
1
Department of Pediatric Dentistry, Faculty of Dentistry,
Chulalongkorn University, 34 Henri‑Dunant Road,
Wangmai, Pathumwan, Bangkok 10330, Thailand
development of secondary caries. Glass ionomer cements
(GICs) are an alternative material for reducing recurrent
caries. However, GIC has a higher risk of fracture when
the restoration is in a load bearing area [4]. Resin-based
ion leaching materials were introduced. Because these mate-
rials release ions, such as fluoride (F), calcium (Ca), and
phosphate (P) and have good mechanical properties, they
may decrease secondary caries development and enhance
remineralization [5–11].
GICs have been widely used as dental restorations. How-
ever, the disadvantages of GICs are high moisture sensitiv-
ity in the initial phase, low initial mechanical properties,
and inferior translucency compared with other restorative
materials [12–14]. Thus, high viscosity GICs (HVGICs)

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were developed to overcome the limitations of conventional
GICs. Several studies have demonstrated that HVGICs main-
tained fluoride release and uptake with improved mechanical
properties [15–17]. In addition, laboratory and clinical trials
demonstrated that GICs in a class II restoration effectively
remineralized adjacent initial interproximal caries [18–22].
A novel material that releases ions essential for reminerali-
zation could be another restorative material choice.
An alkasite restorative material is a resin-based ion
leaching restorative material and is a modified composite
resin. This material consists of alkaline fillers that release
acid-neutralizing ions: fluoride, calcium, and hydroxide
ions. Alkasite materials can be used by bulk placement and
are dual curing, durable, and esthetic [23]. Several studies
revealed that alkasite released phosphate, calcium, and an
acceptable level of fluoride ions [5, 6, 9]. Alkasite led to
significantly reduced enamel demineralization adjacent to
the material compared with a non-ion releasing material
[23, 24].
To the best of our knowledge about the remineralizing
effect of a restoration on adjacent interproximal caries, no
previous studies have been conducted with these newly
introduced restorative alkasite materials. Therefore, the aim
of our study was to evaluate the remineralization of artificial
interproximal enamel caries adjacent to alkasite, HVGIC, or
resin composite in class II restorations. The null hypotheses
were that the surface microhardness of the artificial inter-
proximal enamel caries would not differ after contact with
Fig. 1  Flow chart of the study procedures
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Clinical Oral Investigations (2022) 26:4437–4445
alkasite, HVGIC, or resin composite restorative materials,
and that there would be no difference in surface mineral
deposition on artificial interproximal enamel caries adjacent
to alkasite, HVGIC, or resin composite.
Materials and methods
Specimen preparation
The study’s protocol was approved by the Human Ethics
Committee (Reference number HREC-DCU 2020–014)
and Institutional Biosafety Committee (DENT CU-IBC
018/2020), at the Faculty of Dentistry, Chulalongkorn Uni-
versity, Bangkok, Thailand. Human upper premolar teeth
extracted for orthodontic reasons were used in this study.
The teeth were stored in 0.1% thymol and used within
3 months from the time of extraction [25, 26]. The mesial
and distal surfaces of the teeth were visually examined using
an explorer and stereomicroscope (Olympus, Tokyo, Japan)
at 10 × magnification. Teeth that were free of caries, white
spot lesions, hypoplasia, restorations, cracks, and other
enamel defects were included in the study. The proximal
surfaces of the selected teeth were ground flat and polished
using 1000 grit abrasive paper (BUEHLER, IL, USA) to
expose fresh enamel and remove the fluoride-rich layer that
might interfere with demineralization during pH cycling. A
slow-speed cutting machine (BUEHLER, IL, USA) was used
Clinical Oral Investigations (2022) 26:4437–4445 4439

and were polished using 600, 800, 1000, and 1200 grit abra-
sive paper and fine polished with aluminum oxide powder
to prepare the enamel surface for the microhardness test.
The baseline surface hardness of each sample was measured
using 5 indentations on the left part of the specimen using a
microhardness tester machine (FUTURE-TECH, Kanagawa,
Japan). Samples with a microhardness more than 270 KHN
were included [27]. The sample size was determined based
on our pilot study using G*Power 3.1.9.4 (Heinrich-Heine
Universität, Düsseldorf, Germany) at a power of 0.8 and
confidence level, type I error of 0.05 [28]. The effect size
was 1.479. This calculation indicated that 12 samples per
group were required. According to the previous studies on
the remineralization effect of the fluoride-releasing materials
on artificial proximal caries lesions, they employed a sample
size of 10–16 samples per group [18, 19, 21, 29]. Due to the
availability of permanent premolar teeth and the reliability
of the study, the sample size per group was 22 samples (17
samples each group for determining the surface microhard-
ness and 5 samples each for EDS analysis). The samples
were pooled and assigned using permuted block randomi-
zation to the artificial caries group (n = 5) or the restoration
group (n = 66) that was divided into 3 groups (n = 22): resin
composite, Filtek™ Z350 (3M ESPE, Minnesota, USA);
HVGIC, EQUIA ­Forte® (GC Corporation, Tokyo, Japan);
and Alkasite, Cention N ­ ® (Ivoclar Vivadent AG, Liechten-
stein, Germany). The study flowchart is presented in Fig. 1.

Artificial caries formation

The left one-third of the enamel surface was covered with

Fig. 2  Specimen preparation. A Front view of the block setup to sim-
ulate proximal contact and B top view of the block setup
to section the teeth into 2 × 3 × 3 mm blocks. Seventy-one
samples were embedded in the center of the resin blocks
nail varnish (Revlon, New York, USA) as a control area.
The method used for preparing the demineralization gel
was modified from Alsaffar et al. [30]. The demineraliza-
tion gel contained hydroxyethyl cellulose (1% w/v) in 0.1
M lactic acid adjusted to pH 5.1 with 1.0 M NaOH at 37 °C
in an incubator. The remaining two-thirds of the exposed
enamel surfaces were subjected to artificial caries formation
by immersion in the demineralization gel for 48 h. After
demineralization, each sample was rinsed in deionized

Table 1  The mean and standard deviation of surface hardness at baseline, post-artificial caries lesion formation, post-pH cycling, and the per-
centage surface hardness recovery

Groups Baseline (KHN) Post artificial caries lesion forma- Post-pH cycling (KHN) Percent of surface
tion (KHN) hardness recovery
(%)

Filtek™ Z350 324.333 ± 20.371*,a 16.852 ± 5.018**, a 12.562 ± 4.914 (− 

1.420) ± 1.513
EQUIA ­Forte® 323.067 ± 18.966*,a 17.136 ± 4.876**, a 32.794 ± 10.218 5.151 ± 2.755
Cention ­N® 323.376 ± 16.644*,a 17.267 ± 4.609**, a 50.188 ± 25.121 10.923 ± 7.818
*
 One-way ANOVA test. **Kruskal–Wallis test
Different superscript letters in the same column indicate significant differences between groups (P < 0.05)

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4440 Clinical Oral Investigations (2022) 26:4437–4445

Table 2  The mean rank and Groups Mean rank Mean rank Median Median
median surface hardness Post-pH cycling Percent of surface Post-pH cycling Percent of surface
post-pH cycling and the hardness recovery hardness recovery
percentage surface hardness
recovery Filtek™ Z350 9.18a 9a 12.806 (− 0.653)
EQUIA ­Forte® 29.94b 29.76b 31.868 4.600
Cention ­N® 38.88b 39.24b 44.894 8.084

Using Dunn’s Test

Different superscript letters in the same column indicate significant differences between groups (P < 0.05)

water for 20 s and dried with tissue paper. The specimen
was immersed in artificial saliva for 24 h and the surface
microhardness was measured.
Restorative material preparation
An upper first premolar was prepared with a class II cavity
(4 × 4 × 2 ­mm3) and was embedded in an acrylic block 3 mm
below the cementoenamel junction. An impression of this
was taken using silicone and served as a mold to prepare
the tooth model with a class II cavity using acrylic resin.
The class II cavities were filled according to the manufac-
turers’ instructions with the following restorative materials:
group 1, Filtek™ Z350 resin composite; group 2, EQUIA
­Forte® HVGIC; and group 3, Cention N ­ ® Alkasite restora-
tive material using a Tofflemire Matrix Retainer. Filtek™
Z350 was placed into the cavity in one increment and light-
cured using an LED light-curing unit (3M ESPE, Minne-
sota, USA). Cention ­N® was placed in a single bulk with an
insertion spatula and EQUIA F ­ orte® was delivered using a
syringe because they are capsulated materials. Cention ­N®
and EQUIA ­Forte® self-cured for 5 min and 2.5 min, respec-
tively. After curing, the matrix was removed. To simulate
the contact point between an occluso-proximal restoration
and the adjacent tooth, the convex surface of the restoration
was fixed in contact with the enamel specimen containing
artificial caries (Fig. 2).
pH cycling model
The samples were subsequently subjected to a 7-day pH
cycling. Each cycle consisted of 8-h demineralization and
16-h remineralization. The demineralization solution con-
tained 2.2 mM ­CaCl2, 2.2 mM N ­ aH2PO4, and 0.05 M acetic
acid, at pH 4.6 adjusted using 1 M KOH. The remineralization
solution consisted of 1.5 mM ­CaCl2, 0.9 mM ­NaH2PO4, and
0.15 M KCl, at pH 7 adjusted using 1 M KOH. The samples
were immersed in separate containers with 2 ml of the respec-
tive solutions at room temperature for 7 days [22]. The solu-
tions were freshly prepared for each cycle. Each sample was
thoroughly rinsed with deionized water for 20 s before being
immersed in the remineralization solution. After 7 days, the
treated samples were stored in separate containers in artificial
saliva for 24 h and the surface microhardness post-pH cycling
was measured at the center part.
Surface microhardness assessment
The surface microhardness measurements of each specimen
(n = 17) were taken using a microhardness tester machine with

Fig. 3  Mean rank of the

percentage surface hardness
recovery. Statistical significance
between groups is indicated by
asterisk (*) using Dunn’s test
(P < 0.05)

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Clinical Oral Investigations (2022) 26:4437–4445
A Knoop diamond indenter. Five indentations were performed
on each sample at baseline sound enamel, demineralized
enamel, and the restorative material-contacting enamel sur-
face after 7 days pH cycling. The indentation load was 50 g for
10 s. The distance between indentations was at least 100 µm.
The mean values of the five measurements at baseline, demin-
eralization after artificial carieslesion formation, and after pH
cycling were compared and the percentage surface hardness
recovery was calculated using the equation below [31].
(Hardness post − pH cycling − Hardness post − artificial caries formation) × 100
The percentage surface hardness recovery =
Baseline hardness − Hardness post − artificial caries information
Energy‑dispersive spectroscopy (EDS) and scanning
electron microscope (SEM)
The calcium (Ca), phosphorus (P), and fluoride (F) con-
tents in weight percent (wt%) on the sample surface were
determined using EDS (FEI, Hillsboro, USA). Post-pH
cycling, 5 samples from each group were air-dried, placed
on a carbon sheet, and mounted on aluminum stubs for EDS
analysis. The EDS analysis was performed at an accelera-
tion voltage of 20 kV. The resulting X-ray was processed to
identify the Ca, P, and F concentrations. For each sample,
three 150 × 150 µm areas were randomly selected. After
EDS analysis, the samples were then sputtered coated with
gold and attached to aluminum stubs. The morphology of
the enamel surface was scanned by SEM (FEI, Hillsboro,
USA) at 5000 × and 10,000 × magnification and the most
representative image of the enamel surface was captured.
Statistical analysis
The SPSS 22.0 (SPSS, Chicago, USA) statistical program
was used for statistical analysis. The Shapiro–Wilk test
was used to determine if the data had a normal distribu-
tion (P ≤ 0.05). The differences in the percentage of sur-
face hardness recovery between the groups was compared
using the Kruskal–Wallis Test at the 95% confidence level.
The Dunn’s test was used for between-group comparisons
(P < 0.05). The Ca, P, and F on the enamel surfaces of the
groups were compared by one-way ANOVA test at the 95%
confidence level. The Tukey’s post hoc test was used for
between-group comparisons (P ≤ 0.05).
Results
Surface microhardness
The enamel surface microhardness values were measured
at baseline, post-artificial caries lesion formation, and
4441
post-pH cycling. The percentage surface hardness recovery
was calculated (Table 1). There was no significant differ-
ence in the mean microhardness values between the groups
at baseline (P = 0.979) or post-artificial caries lesion for-
mation (P = 0.946). The Cention ­N® group demonstrated a
significant increase (mean rank = 38.88) in enamel surface
hardness (p < 0.05) post-pH cycling compared with the com-
posite group (mean rank = 9.18). The surface hardness in the
Cention ­N® group was higher compared with the EQUIA
­Forte® group; however, the difference was not significant
(p = 0.080). The mean and mean rank of the percentage sur-
face hardness recovery revealed a similar pattern (Tables 1
and 2). The highest percentage surface hardness recovery
(mean rank = 39.24) was found in the Cention N ­ ® group,
which was not significantly different (p < 0.05) compared
with the Filtek™ Z350 (mean rank = 9) group. Although
the percentage surface hardness recovery in the Cention
­N® group was higher than that of the EQUIA F ­ orte® (mean
rank = 29.76) group, there was no significant difference
(p = 0.063) (Fig. 3).
Elemental analysis and the SEM images
of remineralized surface
The mean and standard deviation of the elemental con-
tents on the enamel surface post-pH cycling are shown in
Table 3. No significant difference in the weight percent of
Ca or P was observed between the groups. The Cention
­N® group demonstrated a significantly increased enamel
surface F content compared with the Filtek™ Z350 group
(p < 0.05). However, no significant difference in F con-
tent was observed between the EQUIA F ­ orte® and Cen-
®
tion ­N groups (p = 0.366). Although the EQUIA F ­ orte®
group F content was not significantly different compared
Table 3  The mean and standard deviation of the elemental contents
measured by EDS analysis on enamel surface of each group post-pH
cycling
Groups Elemental contents (wt%)
Ca/P ratio F
Filtek™ Z350 1.920 ± 0.041 0.831 ± 0.271
EQUIA ­Forte® 1.868 ± 0.053 2.353 ± 1.070
Cention ­N® 1.865 ± 0.043 3.185 ± 1.220 *
One-way ANOVA test
*
  indicate significant differences compared to Filtek™ (p < 0.05)
13
4442
Fig. 4  The mean and standard deviation of the fluoride contents
measured by EDS analysis on enamel surface of each group post-pH
cycling. Statistical significance between groups is indicated by aster-
isk (*) using Tukey’s post hoc test (P < 0.05)
with the Filtek™ Z350 group (p = 0.193), the F content
in the EQUIA ­Forte® group was markedly higher than in
the Filtek™ Z350 group. The Cention ­N® group demon-
strated the highest F content (3.185 ± 1.220%) followed by
the EQUIA ­Forte® (2.353 ± 1.070%), and Filtek™ Z350
(0.831 ± 0.272%) groups (Fig. 4). The SEM images cor-
responded with the elemental analysis results. The enamel
surface with artificial caries exhibited a porous appear-
ance (Fig. 5). The enamel surface morphology adjacent
to the Filtek™ Z350 sample had porosities similar to the
Fig. 5  SEM images analysis of the artificial enamel caries before and after in contact with the restorative materials. Images illustrate the speci-
mens in the artificial enamel caries (A), Filtek™ Z350 (B), EQUIA F ­ orte® (C), and Cention ­N® (D) groups at × 5000 and × 10,000
13
Clinical Oral Investigations (2022) 26:4437–4445
artificial caries. In contrast, the enamel surface adjacent to
the EQUIA F ­ orte® and Cention N ­ ® samples demonstrated
less porosities. Amorphous deposits were seen when the
enamel specimens were remineralized. The greatest amount
of deposited material was observed in the Cention ­N ®
group.
Discussion
Once the proximal tooth surface is cavitated, it needs to be
prepared and restored. Removing the cariogenic bacteria
can alter the environment of the carious tooth to become
less cariogenic and also affect the proximal surface of the
neighboring tooth [32]. The present study is the first to
demonstrate the remineralizing effect of the alkasite restora-
tive material compared with HVGIC and resin composite
in proximal contact with artificial enamel caries using an
in vitro pH cycling model. Based on the protocol in Gug-
lielmi et al., the pH cycling consisted of an 8-h deminerali-
zation period and a 16-h remineralization period, which is
similar to conditions in the oral cavity [22].
The present study design simulated the natural contact
point between the enamel specimen and a restoration. Flat
enamel specimens were used in this study because the flat
surface can be used to measure the surface microhardness.
Furthermore, fixing the convex surface of the restoration in
contact with the enamel specimen containing artificial caries
simulated the contact point between an occluso-proximal
Clinical Oral Investigations (2022) 26:4437–4445
restoration and the adjacent tooth. Therefore, the model used
in this study was similar to natural proximal tooth contact.
The null hypotheses predicting the surface microhardness
and mineral deposition of the artificial interproximal enamel
caries would not differ after contact with alkasite, HVGIC,
or resin composite restorative materials were rejected. Alka-
site significantly increased the surface hardness recovery and
fluoride content of the adjacent enamel caries compared with
composite. These results corresponded with those of Donly
et al., who demonstrated that alkasite generated significantly
less enamel demineralization compared with composite
when photographed under polarized light [24]. However,
this study also found that V­ itremer®, a resin-modified GIC,
had significantly less enamel demineralization than alkasite.
A study reported that alkasite released F and P ions and had
a high capacity for Ca release [6]. In contrast, the present
study did not observe differences in the Ca and P contents
on the enamel specimen surface in each group. This find-
ing may be because the remineralization solution used in
the pH cycling contained a sufficient amount of Ca and P
for remineralization to occur [33]. However, we found that
the amount of F in the alkasite specimens was significantly
higher than the composite specimens but was similar to the
HVGIC specimens. The low monomer conversion and lower
cross-linking density of the resin matrix, which can enhance
fluoride diffusion, may contribute to alkasite’s satisfactory
fluoride release [34]. In contrast, another study reported that
HVGIC released more fluoride ions compared with dual-
cured alkasite [6]. The difference between the curing modes
likely accounts, at least in part, for the disparate outcomes.
Our findings are similar to those of Gupta et al. who deter-
mined that self-cured alkasite released higher amounts of
fluoride ions compared with GIC in acidic pH [7]. The ion
release from the self-cured material was slightly higher than
that from the dual-cured material [23].
The present study used surface microhardness, SEM, and
EDS to assess remineralization. Previous studies have shown
a correlation between the mechanical properties of dental
hard tissue and its mineral content [35, 36]. Hence, hardness
testing is an indirect method used to assess tooth reminer-
alization [37–39]. The surface microhardness results in the
present study corresponded with the SEM and EDS results
that illustrated the mineral deposition gain in the HVGIC
and alkasite samples. However, future studies using other
methods are required assess the remineralization quality.
The alkasite restorative material consists of a separately
packaged powder and liquid that are mixed by hand directly
before use; thus, it was difficult to obtain the correct pow-
der/liquid proportion and mix exactly the same every time.
In contrast, the HVGIC used in the present study comes in
capsules with a consistent powder/liquid proportion. Several
previous studies have demonstrated that varying the powder/
4443
liquid (P/L) mixing ratio in glass ionomer cement affects
the amount of fluoride release [40, 41]. Therefore, slight
differences in the ratio between the powder and the liquid
portion during mixing may affect the fluoride release and the
mechanical properties of this material.
The limitations of our study are the type of GIC used.
Only HVGIC was used in the present study. Another limi-
tation is that we did not evaluate effect of other fluoride-
containing products, such as fluoride mouthwash in com-
bination with the present experiment. A previous study
indicated that fluoride mouthwash also effectively inhibits
initial proximal caries lesions [42, 43].
Based on these limitations, future studies should inves-
tigate the effect of other ion-releasing restorative materi-
als. Additionally, a study demonstrated that hydroxyapatite
was deposited on polymeric composite resin when using
toothpaste containing Zn-carbonate hydroxyapatite [44].
This hydroxyapatite deposition could prevent secondary
caries on the margins of restoration. It would be interesting
to test the materials of the present study in combination
with biomimetic Zn-carbonate hydroxyapatite.
Conclusion
The present study demonstrated that the percentage of
surface hardness recovery and the fluoride content in the
alkasite group was similar to that of the HVGIC group
but superior to the resin composite group. These findings
demonstrate that the alkasite restorative material generates
significant artificial enamel interproximal caries remin-
eralization and could be an alternative restorative mate-
rial to arrest initial enamel lesions in approximal adjacent
surfaces.
Acknowledgements  The authors thank Dr. Kevin Tompkins for manu-
script revision.
Author contribution  Thipthida Theerarath: Methodology, validation,
formal analysis, investigation, resources, data curation, writing-original
draft preparation, funding acquisition. Wannakorn Sriarj: Concep-
tualization, methodology, writing (review and editing), supervision,
project administration, funding acquisition.
Funding  This work was supported by a grant from the Faculty of Den-
tistry, Chulalongkorn University [DRF64005]; CU Graduate School
Thesis Grant [GCUGR1225632041M].
Declarations 
Ethics approval  This study was approved by the Human Ethics Com-
mittee (Reference number HREC-DCU 2020–014) and Institutional
Biosafety Committee (DENT CU-IBC 018/2020), Faculty of Dentistry,
Chulalongkorn University, Bangkok, Thailand.
13
4444 Clinical Oral Investigations (2022) 26:4437–4445

Informed consent  The present study did not involve human partici- trial of class II restoration in permanent teeth comparing ART
pants. with composite resin after 12 months. Clin Oral Investig
23(9):3623–3635
17. de Medeiros Serpa EB, Clementino MA, Granville-Garcia AF,
Conflict of interest  The authors declare no competing interests.
Rosenblatt A (2017) The effect of atraumatic restorative treat-
ment on adhesive restorations for dental caries in deciduous
molars. J Indian Soc Pedod Prev Dent 35:167–173. https://​doi.​
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