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Secondary caries and marginal
adaptation of ion‑releasing
versus resin composite
restorations: a systematic review
and meta‑analysis of randomized
clinical trials
Eman H. Albelasy1,2, Hamdi H. Hamama1,3*, Hooi Pin Chew4, Marmar Montaser1 &
Salah H. Mahmoud1,5
This systematic review was aimed to evaluate occurrence of secondary caries and marginal adaptation
in ion‑releasing materials versus resin composite. Electronic search of PubMed, Scopus, and Open Grey
databases with no date or language restrictions until May 21st, 2021, was conducted. Randomized
clinical trials that compared ion‑releasing restorations versus resin composite were included. For
quantitative analysis, a random‑eects meta‑analysis with risk dierence as an eect measure
and a 95% condence interval was used. Quality of evidence was assessed using The Grading of
Recommendations, Assessment, Development, and Evaluation criteria. The risk of bias was evaluated
using the Cochran Collaboration Risk of Bias tool. The inclusion criteria were met by 22 studies, and 10
studies were included in the meta‑analysis. Three follow‑up periods (1 year, 18 months–2 years, and
3 years) were evaluated. The overall quality of evidence for secondary caries and marginal adaptation
outcomes was low. The results of the meta‑analysis showed no signicant dierence (p > 0.05) in both
outcomes between ion‑releasing materials and resin composite. The occurrence of secondary caries
was not dependent on the nature of the restorative material. It is more likely a complex process that
involves the same risk factors as primary carious lesions.
Over the last decade, remarkable advances in resin composite formulations have been made to address clinical
challenges. Bulk-placement techniques, new ller formulations, and simplied adhesion protocols have resulted
in a more user-friendly application1,2. However, the clinical problems of technique sensitivity, polymerization
shrinkage, and lack of antibacterial properties remained unchanged3–5 and similarly, the main reasons for its
failure remain to be secondary caries and bulk fractures1,6.
Secondary caries can be dened as caries lesions at the margins of existing restorations7 or caries associated
with restorations or sealants (CARS) (secondary caries and caries around restorations are used synonymously in
this review)8,9. e complexity of caries around restorations is related to its multifactorial origin, combining the
pathological pathway of primary carious lesions with the inuence of the formulations of dierent restorative
materials9. It has been reported that thicker biolms accumulate around resin composite than glass ionomer
restorations10. Invivo plaque studies have also shown that the levels of lactic acid-producing bacteria are sig-
nicantly higher around resin composite restorations than on either amalgam or glass ionomer restorations11,12.
OPEN
1Conservative Dentistry Department, Faculty of Dentistry, Mansoura University, Algomhoria Street, Mansoura,
Aldakhlia 35516, Egypt. 2Research Visiting Scholar, Minnesota Dental Research Centre for Biomaterials and
Biomechanics,SchoolofDentistry,UniversityofMinnesota,Minneapolis,MN55455,USA.3Restorative Dentistry
Department,FacultyofDentistry,New-MansouraUniversity,New-Mansoura,Egypt.4Minnesota Dental Research
CentreforBiomaterialsandBiomechanics,SchoolofDentistry,UniversityofMinnesota,Minneapolis,MN55455,
USA. 5ConservativeDentistryDepartment,Facultyof Dentistry,HorusUniversity,New-Damietta,Egypt. *email:
hamdy_hosny@mans.edu.eg
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erefore, uoride-releasing materials that possess remineralization and/or antibacterial properties have gained
popularity in recent years13 with the hope of preventing secondary caries formation.
Conventional glass ionomer cement (GICs) and its evolutions such as: high-viscosity glass ionomer (HV-
GIC), resin-modied glass ionomer (RMGIC), and compomers are the most frequently used uoride-releasing
restorative materials. An inherent disadvantage of GIC is its low fracture toughness, which limits its clinical
applications to low load-bearing areas such as the buccal and lingual surfaces. Nevertheless, increasing the
powder-liquid ratio, and modications in its chemical composition have shown to lead to improved physical
properties and prolonged clinical survival14,15.
Modied versions of the conventionally set GIC such as HV-GIC were introduced with the hope of extend-
ing the indications of GIC to include load-bearing areas on posterior teeth to provide an alternative for patients
with limited resources16–18. Promising 10-years clinical results have recently emerged for HV-GIC used in class
I and II restorations, where no restoration had to be replaced due to unacceptable clinical wear19. In addition to
HV-GIC, glass hybrid materials such as Equia Forte were introduced in 2015. According to the manufacturer,
these materials are modied with highly reactive glass particles of dierent sizes to signicantly increase their
mechanical properties20,21.
Nonetheless, the clinical indications of GIC and its evolutions in multiple-surface restorations in the stress-
bearing posterior regions of the mouth are still limited due to their poor fracture toughness, tensile strength,
wear resistance, and hardness. A recent systematic review reported that the annual failure rates of approximal
or multi-surface GIC restorations were greater than those of single-surface occlusal restorations22. A solution to
counteract this limitation of GIC is to incorporate resin composite restorations (which have superior mechanical
properties than GIC) with reactive llers that can protect the tooth against secondary caries23. Up to press date,
there are several new commercially available ion-releasing composites with claimed bioactivity such as ACTIVA™
BioACTIVE-RESTORATIVE™ (Pulpdent Corporation, Watertown, MA, USA), Cention N (Ivoclar Vivadent,
Schaan, Liechtenstein), and Surel one (Dentsply Sirona). ese materials are relatively recent additions to the
realm of ion-releasing materials, that are claimed by their respective manufacturer, to release sucient amounts
of ions other than uoride to promote remineralization24–26 around restorations. Tiskaya etal. 27, reported sig-
nicant release of Al3+ and Ca2+ ions from Cention N and Activa Bioactive in acidic media of pH 4, which in
turn indicate an ability to protect against secondary caries.
Clinical investigations regarding their ability to inhibit caries around restorations are scarce in the current
literature. While invitro studies have shown that uoride-releasing restorative materials such as GICs can inhibit
tooth demineralization adjacent to restoration margins28–30, the caries inhibitory eect of these new ion-releasing
materials remains unclear. erefore, this systematic review and meta-analysis were aimed to answer the follow-
ing question: Is there a dierence in the occurrence of secondary caries and marginal adaptation in ion-releasing
restorations compared to resin composite?
Materials and methods
e recommendation of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) were
followed in this review31,32.
Eligibility criteria and PICO question. e research question was as follows: Is there a dierence in the
incidence secondary caries and marginal adaptation in ion-releasing restorations compared to resin composite?
e following PICO questions were established:
• Population: patients with permanent dentition in need of restorations.
• Intervention: ion-releasing restorations. From here forth, the term ‘ion-releasing’ will be used in this article
to encompass uoride and all other ion-releasing materials. All GIC derivatives including (RMGIC, HV-GIC,
conventional GIC, and glass hybrid), polyacid-modied composite (compomer), giomer, and any material
stated by the manufacturer to be capable of ion-release will be in the intervention group.
• Comparison: the intervention should be compared with a resin composite restoration applied in conjunction
with any adhesive system.
• Outcomes: caries around restorations and marginal adaptation.
Inclusion criteria.
1. Randomized clinical trials in patients with permanent dentition comparing an ion-releasing material to resin
composite in any form of cavities (Black’s Class I, II, V) and non-carious cervical lesions (NCCLs).
2. Parallel or split-mouth studies.
3. A minimum follow-up period of 1year.
4. Evaluation criteria: FDI criteria and/or USPHS.
5. e investigated materials must be commercially available. Any study investigating discontinued products
was excluded.
Exclusion criteria.
1. Editorial letters, pilot studies, historical reviews, literature reviews, systematic reviews, invitro studies,
cohort, observational and descriptive studies, such as case reports and case series.
2. Randomized clinical trials were excluded if.
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a. Ion-releasing materials were compared to each other with no resin composite restoration as a reference
for comparison.
b. Restorations were done on primary teeth,
c. e follow-up period was less than 1year.
Information source and search strategy. An electronic search within the following databases (Medline
via PubMed and Scopus) was conducted until May 21st, 2021. Grey literature was searched through the Open
Grey database http:// www. openg rey. eu/.
e following keywords were used in the electronic search: “FDI criteria AND randomized clinical trial”,
“modied USPHS criteria AND randomized clinical trials”, “Secondary caries OR caries adjacent to restorations
and randomized clinical trials”, “marginal adaptation and randomized clinical trial”, “ion releasing restorations
OR bioactive resin composite OR bio interactive restorations AND clinical trials”. To identify ongoing clinical
trials, we also searched the ClinicalTrials.gov website. e outcome of the search among the abovementioned
databases was comprehensively checked and duplicated results was excluded.
To minimize publication bias, no language or publication date restrictions were applied. Two reviewers (E.H.
and H.H.) independently extracted data and assessed their eligibility and risk of bias. Any disagreements were
resolved by consulting a third reviewer (H.C.).
Study selection and assessment of eligibility. According to the search strategy, assessment of the
eligibility of trials was performed by the two reviewers according to the relevance of the title. Abstracts of studies
that could not be excluded based on the title were retrieved and evaluated. At the nal stage of evaluation, full
texts were assessed to determine if they met the predetermined inclusion criteria. e included studies received
an identication code composed of the rst author’s last name and the year of publication.
Two reviewers extracted data from included studies such as the number of patients and restorations per
group, intervention, and comparator, follow-up period, study design, evaluation criteria, adhesive strategy, cavity
design, isolation technique, patient’s age, settings, and location of data collection. In studies that reported multiple
follow-up periods, data from the longest follow-up were extracted. If more than one type of resin composite was
used, the data were combined into a single entry. For ion-releasing restorations, GIC-based restorations (HVGIC,
glass hybrid, and RMGIC) were combined into a single entry and compomer restorations were pooled together.
Assessment of risk of bias. e Risk of Bias (RoB) of the included studies was assessed using the Cochrane
Collaboration Risk of Bias Tool (version 2.0) for RCTs33. e six domains of the RoB Tool are assessment of
random sequence generation, allocation concealment, blinding of participants and personnel, blinding of the
outcome assessors, incomplete outcome data (attrition bias), selective outcome reporting, and other sources of
bias. In this study, the other sources of bias domain was not included. Each entry received a judgment of low,
unclear, or high risk of bias. At the study level, a study was considered at low risk of bias if all 5 domains of the
RoB tool for each outcome were at low risk of bias. If one or more domains were judged to have unclear risk,
the study was judged to have unclear risk. If at least one item was considered at high risk of bias, the study was
considered to have a high risk of bias.
Assessment of quality of evidence. e condence in evidence was evaluated using the Grading of
Recommendations Assessment, Development, and Evaluation (GRADE)34. According to GRADE, the body of
evidence can be rated as high, moderate, low, or very low. e GRADE pro-Guideline Development Tool (www.
grade pro. org) was used to create a summary-of-ndings table.
e strength of cumulative evidence was assessed based on, the risk of bias, inconsistencies, indirectness,
imprecision, and publication bias. e data were summarized in the summary of ndings (Table2). e qual-
ity of evidence for the rst 4 domains may be downgraded by 1, 2, or 3 levels based on “serious or very serious
risks. Publication bias may either be suspected or undetected. In the case of suspected bias, downgrading by 2
levels was made35,36.
Synthesis of data. Data were analysed using Revman 5.4 (Review Manager Version 5.4, e Cochrane
Collaboration, Copenhagen, Denmark). Data from included studies were either dichotomous for the “Second-
ary Caries” outcome measure or ordinal for the “Marginal Adaptation” outcome measure. Marginal adaptation
data were dichotomized to NO representing Alpha and Bravo scores of the modied USPHS criteria, and scores
1 and 2 of the FDI criteria, or YES corresponding to Charlie and Delta scores of the modied USPHS criteria,
and 3, 4, and 5 scores of the FDI criteria. Risk dierences as an eect measure with 95% condence intervals
and random eects model were employed. Heterogeneity was evaluated using the Q test and I2 statistics, where
25%, 50%, and 75% represent low, moderate heterogeneity, and high heterogeneity respectively. For both the
outcomes (secondary caries and marginal adaptation), data from 3 follow-up periods were included, i.e., 1year,
18months—2years, and 3years. For secondary caries outcome, two analyses were performed, one with all types
of cavities, and one for load-bearing cavities.
Results
Search details. e initial search in the databases resulted in 3744 studies being identied aer dupli-
cates exclusion. Aer title screening, 3584 articles were excluded, and the remaining 160 abstracts were further
assessed for eligibility. Articles that had multiple reports corresponding to dierent follow-up periods were com-
bined into a single entry and the data of the longest follow-up were included in this study. is process culmi-
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nated in 39 studies that were to be progressed to full-text analysis. Subsequent full-text analysis of these studies
resulted in 22 studies that met the inclusion criteria (Fig.1).
Risk of bias evaluation. Overall, 3 studies were deemed to have a low risk of bias19,37,38, 3 studies showed39–41
unclear risk of bias while the remaining 16 studies had a high risk of bias. Seven studies17,42–47 did not report
random sequence generation, while 50% of the included studies reported allocation concealment. Performance
bias was unclear in the majority of studies (16 out of 22), while outcome assessment was blinded in all studies
except for 343,48,49. No attrition bias was noticed in any of the included studies except for one44, which did not
adequately report the number of dropouts (Fig.2).
Figure1. Prisma ow chart of the study selection process.
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Included studies characteristics. e characteristics and methodological assessment of the 22 included
studies are summarized in Table1. In 15 of the included studies16,19,37,38,41–44,46–48,50–53, split-mouth design was
employed while 7 studies reported a parallel study design17,39,40,45,49,54,55. Most of the studies employed the modi-
ed USPHS criteria for restorations evaluation except for 4 studies16,17,50,51 that used FDI criteria. One study43
used the McComb etal., criteria56. Five studies used HV-GIC16,17,19,39,49. Two studies used glass hybrid38,51. Resin-
modied glass ionomer was used in 9 studies37,41–43,45,50,52,54,57, while 2 studies used conventional GIC43,53. Com-
pomer (poly-acid modied composite) was used in 7 studies40,44–48,54. Most of the studies used nano- or micro-
hybrid composite. Bulk-ll composite was used in one study39. Nano-lled composite was used in 2 studies46,57
while one study used micro-lled composite44. Most follow-up periods ranged between 2 and 3years. Long-
term follow-up was reported in 2 studies19,40 which had a follow-up period of 10 and 7years respectively. One
study41 was terminated aer 1year due to an unacceptable failure rate. Class II cavities were reported in 7
studies19,39,41,47,49,51. Class I cavities were evaluated in 3 studies 17,19,41. Non-carious cervical lesions were evaluated
in 11 studies16,38,42,44–46,48,50,52,53,57. Class V carious lesions were evaluated in 4 studies37,40,43,54. For HV-GIC, glass
hybrid, and conventional GIC, Cavity conditioner of poly-acrylic acid was used in all studies except 2 which did
not report any type of pre-treatment38,53. For RMGIC, 2 studies used 37% phosphoric acid etching for 5 s37,41.
Two studies used Vitremer primer45,52 while another study used GC cavity conditioner for RMGIC, and Ketac
nano primer for nano-lled RMGIC42,57. For Compomer, 5 studies used self-etch adhesive (SE)40,45,46,48,54, while
2 studies used etch-and-rinse adhesive (ER)44,47.
For resin composite,8 studies used ER adhesive system16,37,42–45,47,52,57 while 9 studies used SE
adhesives17,19,40,41,46,48,50,51,54. Two studies used a universal adhesive in selective etch mode38,49, 1 in SE mode39,
and 1 in ER mode53. For moisture control, cotton rolls and saliva ejectors were reported in the majority of studies
except for 3 studies that used rubber dam isolation44,51,52.
Patients in all studies had no systemic diseases except two43,53. In one study53, patients were required to have
at least one systemic disease and the other one43 included subjects who were xerostomic, head and neck, cancer
patients who received radiation therapy. Ten studies16,19,37–39,41,49–51,53 were published in the years (2018–2020) with
6 in 2020, 3 in 2019, and 1 in 2018. No studies were identied from January to May of 2021. Five studies17,40,43,52,57
were published between 2010 and 2014. Seven studies42,44–48,54 were published before 2010.
Descriptive analysis. Studies that reported secondary caries and marginal adaptation in dierent follow-
up periods were included in the meta-analysis (Figs.3, 4, 5). For secondary caries outcome for all types of
cavities, the meta-analysis was grouped as follows: ion releasing materials (GIC) vs resin composite (RC) with
the following 3 follow-up periods, i. e. 1year, 18–24months, and 3years. For secondary caries in load-bearing
cavities, ion-releasing material (GIC and compomer) vs resin composite, and data were extracted from the last
follow-up.
e dierence in the number of studies in each follow-up is attributed to whether the outcome was reported
by the authors. For marginal adaptation outcome, GIC vs resin composite comparison was evaluated at the same 3
follow-up periods. secondary caries was not reported in all studies that compared compomer and resin composite
at dierent follow-up periods. erefore, no meta-analysis was performed for compomer vs resin composite
comparison. Out of a total of 1448 GIC restorations, only 15 showed secondary caries with a percentage of 0.8%.
Similarly, 16 composite restorations failed due to caries out of 1637 with a percentage of 0.9%. In all studies that
compared compomer and resin composite, no occurrence of secondary caries was observed over the follow-up
periods which ranged between 2 and 3years.
Meta‑analysis. Secondary caries. e risk dierence for the comparison between GIC and RC for the
1-year and18 month–2years follow-up periods was -0.00 with 95% CI between [− 0.1–0.01]. e 3-year follow-
up risk dierence was 0.00 with 95% CI between [− 0.2–0.02] with no occurrence of secondary caries in both
arms. ere was no statistically signicant dierence (P = 0.61) between GIC and RC in secondary caries devel-
opment at any of the follow-up periods. For a total of 1448 GIC restorations, 15 failed due to secondary caries,
in comparison with 16 out of 1637 composite restorations. Overall heterogeneity was low with I2 = 0%. (Fig.3).
For secondary caries in load-bearing cavities, the risk dierence was 0.0 with 95% CI between [− 0.01–0.02].
No statistically signicant dierence (P = 0.77) was found between ion-releasing material and secondary caries.
Marginal adaptation. e risk dierence for the 1-year follow-up was 0.0.1 with 95% CI between [− 0.02–0.03].
Heterogeneity was high with an I2 = 75%. No statistically signicant dierence (p ˃ 0.5) was found between the 2
materials. At 18months–2years follow-up, the risk dierence was 0.03 with 95% CI between [− 0.02–0.08]. Het-
erogeneity was high with an I2 = 94%. At the 3-year follow-up, the risk dierence was 0.00 with 95%CI between
[− 0.02–0.02]. Heterogeneity was low with an I2 = 0%.
e overall risk dierence was 0.01 with 95%CI between [− 0.01–0.03]. Out of a total of 1255 GIC restora-
tions, 78 showed unacceptable marginal adaptation compared to 16 out of 1470 RC restorations. No statistically
signicant dierence was found between the 2 materials. Overall heterogeneity was high with an I2 = 84%. (Fig.4).
GRADE quality of evidence. Assessment of the quality of evidence for secondary caries and marginal adapta-
tion outcomes for the 3 follow-up periods (1year, 18–24months, and 3years) was low. is nding suggests
that the condence in the eect estimate is limited, and that further research is likely to have an impact on the
condence of the estimate of eect (Table2).
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Figure2. Risk of bias summary: authors’ judgments about each risk of bias item for each included study. Filled
Green circle Low ROB Filled Red circle High ROB Filled Yellow Circle Unclear ROB.
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Study ID
1. Ion-
releasing
material 2. Type of
composite 3. Evaluation
criteria
4. Number of
restorations/
per group
5. Total
number of
restorations
and/patients 6. Follow-up
period
7. Location/
settings
of data
collection 8. Trial
design 9. Recall
rate
10. Secondary
caries
detection
Balkaya etal.39 Glass hybrid:
Equia Forte
Fil a
1.Bulk-ll
resin compos-
ite: Filtek Bulk
Fill Posterior a
2. Micro
hybrid
composite:
Charisma
Smart c
Modied USPHS
1. Equia
Forte/34
2. Filtek Bulk-
ll /38
3. Charisma
smart /37
109/54 2 Yea rs Turkey/Uni-
versity Parallel 100%
Visual-tactile
with mirror,
intraoral pho-
tographs, prob
and bitewing
radiographs
Gurgan etal.19 1. HVGIC:
Equia Fil a
1. Microhy-
brid resin
composite:
Gradia Direct
Posterior a
Modied USPHS
1. Equia Fil/40
class I, 30
class II
2. Gradia
Direct
Posteior/40
class I, 30
class II
140/59 10 Years Turkey/Uni-
versity Split-mouth 88.1%
Visual-tactile
with mirror,
coloured pho-
tographs and
prob
Koc Vural
etal.37 1. RMGIC:
Riva LC J
1. Microhy-
brid compos-
ite: Spectrum
TPH3 e
Modied USPHS 1. Riva LC/55
2. Spectrum
TPH3/55 110/33 3 Ye ar s Turkey/Uni-
versity Split-mouth 90.91%
Visual-tactile
method with
mouth mirror
and explorer
under the dental
light unit
Koc Vural
etal.38
Glass hybrid:
Equia Forte
Fil a
1. Nanolled
composite:
Ceram X One
Universal e
Modied USPHS
1. Equia Forte
Fil/74
2. Ceram X
One/74
148/52 2 Yea rs Turkey/Uni-
versity Split-mouth 88% Visual with the
aid of coloured
photographs
Miletić etal.51 Glass hybrid:
Equia Forte
Fil a
1. Nanohybrid
composite/
Tetric Evo-
ceram c
FDI
1. Equia
Forte/179
2. Tetric Evo-
ceram/178
358/184 2 Yea rs
Multicenter:
Croatia, Italy,
Turkey, and
Serbia/Uni-
versity
Split-mouth 90.6%
Visual-
tactile with
(magnication
2.5X), mirrors,
and very thin
(250-μm-thick)
dental probes
Oz etal.53 Conventional
GIC: Fuji
Bulk a
1.MFR Hybrid
Composite/
Gaenial Poste-
rior a
Modies USPHS 1. Fuji Bulk/67
2. Gaenial
Posterior/67 134/30 1 Ye ar Turkey/Uni-
versity Split-mouth 93%
Visual-tactile
with mirrors,
probes, and air
streams
Celik etal.16 1. HVGIC:
Equia Fil a
1.MFR Hybrid
Composite
G-aenial
Posterior a
FDI 1. Equia Fil /67
2. G-aenial/67 134/22 3 Yea rs Turkey/Uni-
versity Split-mouth 82% Visual-tactile
using a mirror
and an explorer
Menezes-Silva
etal.49 1. HVGIC:
Equia Fil a2. Filtek Z350
XT Universal bModied USPHS 1. Equia Fil/77
2. Filtek
Z350/77 154/154 1year Brazil/17 pub-
lic primary
schools Parallel 94.8%
Visual-tactile
with photo-
graphs, mirror,
and ballpoint
periodontal
prob
Van Dijken
etal.41
1. RMGIC:
Activa Bioac-
tive f
1. Nanolled
composite:
Ceram X eModied USPHS 1. Activa
Bioactive/82
2. Ceram X/82 164/67 1 Ye ar Sweden/Uni-
versity Split-mouth 96.3%
Visual-tactile
using mirror
and explorer
and radiographs
one-year recall
Jassal etal.50 1. RMGIC:
GC II LC a
1. Microne
hybrid comp-
iste/Solar X aFDI
1. GC II LC/98
2. Solar X , pas-
sive adhesive
application/98
3. Solar X, rig-
ouros adhesive
application/98
294/56 18 Months India/n.r Split-mouth 90.81%
Visual using
dental-operating
microscope at
1 × magnica-
tion
Diem t al.17 1. HVGIC:
Fuji IX GP
Extra a
1. Microne
hybrid Com-
posite: Solar aFDI
1. Fuji IX GP
Extra/87
2. Fuji IX GP
Extra with
G-coat plus/84
3. Solar /83
254/91 3 Yea rs
Vietnam/Pri-
mary school
in semi-rual
area
Parallel 77.9%
Visual using
headlight,
natural light,
and digital
photographs
Van Dijken
etal.40 1. Compomer:
Dyract AP e
1. Hybrid
compiste/Tet-
ric Ceram cModied USPHS
1. Dyract
AP/69
2. Tetric
Ceram/70
139/60 7 Yea rs University Parallel 97.1% Visual-tactile
using a mirror,
and an explorer
Perdigão
etal.57
1. RMGIC:
Fuji II LC a
2. Nanolled
RMGIC:
Ketac Nano b
1. Nanolled
composite:
Filtek Suprem
Plus b
Modied USPHS
1. Fuji II LC/31
2. Ketac
Nano/30
3. Filtek
Suprem/31
92/33 1 Yea r Brazil/Uni-
versity Parallel 84.8%
Visual using
a mirror and
intra-oral-
coloured
photographs at
1.5 × magnica-
tion
Continued
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Study ID
1. Ion-
releasing
material 2. Type of
composite 3. Evaluation
criteria
4. Number of
restorations/
per group
5. Total
number of
restorations
and/patients 6. Follow-up
period
7. Location/
settings
of data
collection 8. Trial
design 9. Recall
rate
10. Secondary
caries
detection
De Moor
etal.43
1. Conven-
tional GIC:
Ketac Fil b
2. RMGIC:
Photac Fil b
1. Microhy-
brid compiste:
Herculite
XRV d
McComb etal.,
criteria
1. Ketac Fil/35
2. Photac Fil/35
3. Herculite/35 105/35 2 Ye ar s Belgium/Pri-
vat practice Split-mouth 77.1% Tactile using an
explorer
Santiago
etal.52 1. RMGIC:
Vitremer b
2. Nanohybrid
composite:
Tetric Ceram cModied USPHS 1. Vitremer/35
2. Tetric
Ceram/35 70/35 2 Yea rs Brazil/Uni-
versity Split-mouth 93.3% Visual-tactile
using a mirror,
and an explorer
Pollington
etal.48 1. Compomer:
Hytac b
1. Univer-
sal Hybrid
composite:
Pertac II b
Modied USPHS 1. Hytac/30
2. Pertac II/30 60/30 3 Yea rs United
Kingdom/
University Split-mouth 100% Visual-tactile
(no details are
mentioned)
Türkün etal.46 1. Compomer:
Dyract e
1. Nanolled
compos-
ite: Filtek
Supreme b
USPHS 1. Dyract/50
2. Filtek
Supreme/50 100/24 2 Ye ar s Turkey/Uni-
versity Split-mouth 100%
Visual-tactile
using a mirror,
an explorer and
radiographs
Gallo etal.44 1. Compomer:
F 2000 b
1. Microlled
composite:
Silux Plus bModied USPHS
1. F 2000 + Sin-
gle bond
(ER)/30
2. F 2000 + SE
primer/30
3. Silux
Plus + Single
bond/30
90/30 3 Yea rs USA/Univer-
sity Split-mouth 100% Visual-tactile
(No details are
mentioned)
Onal etal.45
1. RMGIC:
Vitremer b
2. Compomer:
F 2000 b
3. Compomer:
Dyract e
1. Universal
composite:
Valus Plus bModied USPHS
1. Vitremer /24
2. F 2000/38
3. Dyract 64
4. Valus
Plus/22
130/30 2 Yea rs Turkey/Uni-
versity Parallel ara> 93.8% Visual-tactile
(no details are
mentioned)
Brackett
etal.42 1. RMGIC:
Fuji II LC a
1. Microhy-
brid compos-
ite/Z250 bModied USPHS 1. Fuji II LC/37
2. Z250/37 74/24 2 Yea rs Mexico/Uni-
versity Split-mouth 73% Visual-tactile
(no details are
mentioned)
Wucher etal.47 1. Compomer:
Dyract e
1. Microhy-
brid compiste:
Spectrum
TPH e
USPHS
1. Dyract/23
2 Dyract
covered with
Spectrum /23
3. Spectrum
TPH/23
69/23 3 Yea rs South Africa/
Private
practice Split-mouth 86.9%
Visual-tactile
using mirror,
periodontal rob,
and periapical
radiographs at
1-year recalls
Folwaczny.,
etal.54
1. Compomer:
Dyract e
2. RMGIC:
Fuji II LC a
3. RMGIC:
Photac Fil b
1. Hybrid
Compoiste:
Tetric Ceram cModied USPHS
1. Dyract/79
2. Fuji II LC/51
3. Tetric
Ceram/36
197/37 2 Yea rs Germany/
University
setting Parallel N.r Visual-tactile
using mirrors
and a prob
Study ID 10. Black’s
classication
11. Cavity
design and
size
12. Gingival
margin location/
enamel bevel 13. Moisture
control
14. Adhesive
technique/
Composite
15. Adhesive
technique/
Ion-releasing
material
16. Patient’s
age
Mean ± SD
[Range], in
years
Balkaya etal.39 Class II Conservative
slot design Enamel/no bevel Cotton pellets
and suction Single Bond
Universal b/SE
Polyacrylic
acid condi-
tioner a2220–32
Gurgan etal.19 Class I and II Conservative Enamel/no bevel C otton rolls G-bond a/One
step SE
Polyacrylic
acid condi-
tioner a2415–37
Koc Vural
etal.37 Class V (cari-
ous) Conservative Dentine/no bevel Cotton rolls
and saliva
ejector
Prime & Bond
NT e/2-step
ER
37% phos-
phoric acid
for 5s 52.69 ± 9.737–88
Koc Vural
etal.38 Class V
(NCCL)
Wedge
shaped, and
saucer-shaped N.R Cotton rolls
and saliva
ejector
Prime & Bond
Elect One e/
Univeral
adhseive
with selective
enamel etch-
ing
No precondi-
tioning 55 ± 8.340,42–71
Miletić
etal.51ara> Class II Conservative,
moderate to
large Enamel/no bevel
Rubber dam
for composite
High suction
and cotton roll
for GIC
Adhese c/2-
step SE Polyacrlic acid
condition a> 18
Oz etal.53 Class V
(NCCL) Non-retentive Enamel + dentine/
n.r Cotton rolls
G-premio
bond a/Uni-
versal adhesive
in ER mode
No pre-
treatment
61.8 ± n.r
Patient had at
least one sys-
temic disease
Continued
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Discussion
is systematic review discussed the occurrence of secondary caries in ion-releasing materials versus resin com-
posite. Glass ionomer and its derivatives are the most clinically reported ion-releasing materials. Compomer was
less frequently used. e results of the meta-analysis showed no signicant dierence between the secondary
caries in resin composite and all derivatives of GIC.
Secondary caries is inuenced by several factors with the most frequent ones being: the location of the lesion
(cervical, proximal, or occlusal), patient’s caries risk, age, and socioeconomic status, operator’s skills variation,
and detection methods and criteria58. e majority of studies included in this review were conducted in university
settings with trained operators and under standardized conditions with patients who demonstrated moderate
oral hygiene. is could explain the low number of events. Secondary caries was found to be more frequent in
Study ID 10. Black’s
classication
11. Cavity
design and
size
12. Gingival
margin location/
enamel bevel 13. Moisture
control
14. Adhesive
technique/
Composite
15. Adhesive
technique/
Ion-releasing
material
16. Patient’s
age
Mean ± SD
[Range], in
years
Celik etal.16 Class V
(NCCL) Wedge or
saucer-shaped Dentine/no bevel
Cotton rolls,
retraction cord,
and a saliva
aspirator
Optibond
FLd/a 3-step
ER
Polyacrylic
acid a47.8 ± nr34–62
Menezes-Silva
etal.49 Class II GIC/ATR
Composite/
conservative
Dentine/retention
grooves for GIC Cotton rolls Single Bond
Universal bPolyacrylic
acid aN.r8–19
Van Dijken
etal.41 Class I and II Retentive
cavity N.r/no bevel Cotton rolls
and suction Xeno select
e/1- step SE
Etching for
5s with phos-
phoric acid 58.3 ± n.r37–85
Jassal etal.50 Class V
(NCCL) Non-retentive Enamel + dentine/
no bevel
Cotton rolls
and retraction
cord
G-bond a/1-
step SE Polyacrylic
acid > 18
Diem etal.17 Class I Adhesive cav-
ity preparation No bevel Cotton rolls G-bond a/1-
step SE Polyacrylic
acid
N.r11,12 with
occlusal caries
in permanent
rst molars
Van Dijken
etal.40 Class V (cari-
ous) Non-retentive Dentine/no bevel Cotton rolls
and saliva suc-
tion device
Xeno III e/1-
step SE Xeno III e/1-
step SE 61.5 ± n.
r40,43–83
Perdigão
etal.57 Class V
(NCCL) Non-retentive n.r/no bevel Cotton rolls FGM k/2-step
ER
1. Ketac Nano
primer b
. Polyacrylic
acid condi-
tioner with
Fuji LC
48.7 ± n.r30–78
De Moor
etal.43 Class V (cari-
ous)
Conventional
cavity prepa-
ration Enamel/bevel N.r Optibond FL
d/3-step ER Polyacrylic
acid a
45 [n.r]
Head and
neck cancer
patients
Santiago
etal.52 Class V
(NCCL) Non-retentive Enamel/no bevel Rubber dam Excite c/2-step
ER Vitremer
Primer bN.r 18–50
Pollington
etal.48 Class V
(NCCL) Non-retentive Enamel + dentine/
no bevel
Cotton rolls
and high suc-
tion
Prompt L-Pop
b/1-step Prompt L-Pop
b/1-step 54 [N.r]
Türkün etal.46 Class V
(NCCL) Non-retentive No bevel Cotton rolls
and retraction
cord
Clearl
protect y/2-
step SE
Clearl
protect y/2-
step SE 44 25–54
Gallo etal.44 Class V
(NCCL) Non-retetnive Enamel + dentine/
bevel Rubber dam Single Bond
b/2-step ER
1. Single Bond
b/2-step ER
2. F 2000 b/SE N.r
Onal etal.45 Class V
(NCCL) Non-retentive Enamel + dentine/
no bevel Cotton rolls
and suction Scotchbond
b/3-step ER
1. Vitremer
Primer b
2N.r 27–63
Brackett
etal.42 Class V
(NCCL) Non-retentive Enamel + dentine/
n.r
Cotton rolls
and retraction
cord
Single Bond
b/3-step ER Polyacrylic
acid a47 ± n.r 28–72
Wucher etal.47 Class II Conventional
design N.r/no bevels Cotton rolls
and saliva
ejector
Prime and
Bond 2.1 e/2-
step ER
Prime and
Bond 2.1 e/2-
step ER N.r 25–61
Folwaczny
etal.54
Class V
(carious and
NCCL) Non-retentive Enamel + dentine/
bevel Cotton rolls Syntac C/3-
step ER PSA Dyract
e/2-step SE N.r 26–66
Table 1. Characteristics of the included studies. a: GC,Tokyo, Japan, b: 3M. c: Heraeus Kulzer, Ha-nau,
Germany. d: Kerr—Sybron Gmbh, Karlsruhe, Germany. e: Dentsply,Konstanz, Germany. C: Vivadent, Schaan,
Liechtenstein), f: Pulpdent, Watertown, MA, USA). j: SDI, Bayswater, Australia). y: Kuraray; Osaka, Japan).
k: Joinville, Brazil. n.r: not reported. ER: Etch-and-rinse. SE: Self-etch. ART: atraumatic restorative technique.
RC: resin composite.
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practice-based settings7. is could be attributed to the technique sensitivity of composite placement that requires
highly skilled and calibrated operators which is oen the case in university settings59. Regarding operative pro-
cedures, the majority of studies in this review used cotton rolls and saliva ejectors for moisture control while
only 3 studies reported rubber dam isolation. Previous literature reported no signicant dierence between the
survival of composite restorations performed under either of the isolation protocols60.
Figure3. Forest plot of comparison: Ion releasing restoration (GIC) versus resin composite, outcome: 1.1
Secondary caries for all types of cavities.
Figure4. Forest plot of comparison: Ion releasing restoration versus resin composite, outcome: 1.2 Secondary
caries for load-bearing cavities.
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e location of the lesion is an important factor that could explain the generally low incidence of events.
Around 45% of the included studies involved NCCL which are less aected by secondary caries than posterior
occlusal and proximal cavities59. Secondary caries is reported to be more frequent with deep proximal restora-
tions with gingival margins extending beyond the cementoenamel junction with dentine and cementum as the
substrate61,62. Furthermore, the placement of such restorations is highly technique sensitive and isolation in every
restorative step cannot be strictly followed9.
e Patient’s caries susceptibility is crucial in secondary caries development, as primary caries and secondary
caries are inherently the same diseases and consequently patients with high caries risk are more suspectable to
secondary caries63. e ndings of this review were based on the results of studies performed on a population
of healthy individuals with good to moderate oral hygiene and with no debilitating conditions. One exception
is the study by De Moor etal.43, in which the population was head and neck xerostomic cancer patients who
received radiation therapy. De Moor etal. 43, reported a signicantly higher failure rate due to secondary caries
in resin composite restorations in comparison with conventional GIC. Nevertheless, the ndings of this study
cannot be generalized as this population is highly specic. However, the dierence in the performance of dierent
materials in populations with compromised oral health indicates that patient factors could be more inuential
than the choice of material.
Adhesive strategy and interfacial gap formation were speculated to play a role in secondary caries develop-
ment. Gaps at the margins of restorations can permit bacterial invasion and biolm accumulation along the
tooth/restoration interface64. However, until now there is no Conesus in the literature regarding the role of gaps
in secondary caries development. In a study by Kidd etal.,65, it was suggested that microleakage cannot solely
induce active demineralization beneath a restoration, only when bacterial invasion takes place at the composite-
restoration interface, the size of the gap becomes pertinent.
e durability of the adhesive interface is critical for the survival of resin composite restorations, especially
with dentin margins. Several attempts have been made to increase the durability of adhesives to dentine including
using MMPs inhibitors, biomimetic remineralization, and increasing the hydrophobicity of the adhesive66–68. e
adhesion protocols in this systematic review varied between etch-and-rinse (9 studies) and self-etch adhesives
Figure5. Forest plot of comparison: Ion releasing restoration (GIC) versus resin composite, outcome: 1.3
marginal adaptation.
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(8 studies), while 2 studies used universal adhesives in selective etch mode38,49, one in SE mode39 and one in ER
mode53. e ndings of this systematic review suggest that regarding secondary caries development, all adhesive
strategies performed similarly considering the low number of events. In a previous study that utilized a short-
term invitro biolm model69, the adhesive type aected carious lesion development and progression in gaps.
However, a recent systematic review and Network meta-analysis showed similar performance of all adhesive
strategies in preventing secondary caries70. It is worth mentioning that the impact of adhesive strategy/type on
secondary caries development was not assessed quantitatively in this review, considering the overall scarcity of
secondary caries occurrence in the included follow-up periods.
e short follow-up period (2–3years) in the majority of studies might have contributed to an overall low
incidence of events. Longer-term follow-up clinical trials showed an increased reporting of secondary carious
lesions71,72. According to the ndings of a recent review59, the highest mean incidence of secondary caries devel-
opment was recorded aer ve years. Interestingly, the only long-term 10-year follow-up study for posterior
restorations (class I and II) in this review19, did not report failure due to secondary caries for composites and glass
ionomer restorations over the 10-year observational period. Furthermore, the detection methods and criteria of
evaluation might have played a role in reporting secondary caries. According to a systematic review by Brouwer
etal.73, only visual assessment would mean that 40% of secondary carious lesions will be missed, while 20% of
Table 2. Quality assessment of the included studies according to the GRADE tool. CI: Condence interval.
A: most of the information is from studies with an unclear or high risk of bias. B: Control and intervention
arms had no events. High quality: We are very condent that the true eect lies close to that of the estimate
of the eect. Moderate quality: We are moderately condent in the eect estimate: e true eect is likely to
be close to the estimate of the eect, but there is a possibility that it is substantially dierent. Low quality: Our
condence in the eect estimate is limited: e true eect may be substantially dierent from the estimate of
the eect. Very low quality: We have very little condence in the eect estimate: e true eect is likely to be
substantially dierent from the estimate of eect.
Certainty assessment Summary of ndings
Participants
(studies)
Follow up Risk of bias Inconsistency Indirectness Imprecision Publication
bias
Overall
certainty of
evidence
Study event rates (%)
Relative
eect (95%
CI)
Anticipated absolute
eects
With resin
composite
restorations
With Ion
releasing
material
(GIC)
Risk with
resin
composite
restorations
Risk
dierence
with Ion
releasing
material
(GIC)
Secondary caries—1-year follow-up
1677 (12
RCTs) SeriousANot serious Not serious SeriousBnone ⨁⨁◯◯
LOW 8/880 (0.9%) 6/797 (0.8%) Not esti-
mable 9 per 1000
0 fewer per
1000
(from 10
fewer to 10
more)
Secondary caries—18months to 2years follow-up
1087
(8 RCTs) SeriousANot serious Not serious SeriousBnone ⨁⨁◯◯
LOW 8/594 (1.3%) 9/493 (1.8%) Not esti-
mable 13 per 1000
0 fewer per
1000
(from 10
fewer to 10
more)
Secondary caries—ree-year follow-up
321
(3 RCTs) SeriousANot serious Not serious SeriousBnone ⨁⨁◯◯
LOW 0/163 (0.0%) 0/158 (0.0%) Not esti-
mable 0 per 1000
0 fewer per
1000
(from 20
fewer to 20
more)
Marginal adaptation—One-Year follow-up
1386
(9 RCTs) SeriousANot serious Not serious SeriousBnone ⨁⨁◯◯
LOW 6/748 (0.8%) 30/638
(4.7%) Not esti-
mable 8 per 1,000
10 fewer per
1000
(from 30
fewer to 20
more)
Marginal adaptation—18months to 2years follow-up
1018
(7 RCTs) SeriousANot serious Not serious SeriousBnone ⨁⨁◯◯
LOW 10/559
(1.8%) 48/459
(10.5%) Not esti-
mable 18 per 1,000
30 fewer per
1000
(from 80
fewer to 20
more)
Marginal adaptation – ree-year follow-up
321
(3 RCTs) SeriousANot serious Not serious SeriousBnone ⨁⨁◯◯
LOW 0/163 (0.0%) 0/158 (0.0%) Not esti-
mable 0 per 1,000
0 fewer per
1000
(from 20
fewer to 20
more)
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sound surfaces will be misdiagnosed as carious. Until now, there is no clear consensus on what constitutes a
secondary carious lesion that requires intervention8,9.
While the ndings of invitro studies74,75 reported a reduced risk of secondary caries in ion-releasing resto-
rations such as GICs and their derivatives, the relation between the restorative material and secondary caries
development is not clear in clinical settings. It is worth mentioning that clinical reporting in the form of ran-
domized clinical trials on the recently developed ion-releasing materials is still scarce. Developments such as
RMGIC with ionic resin matrix (Activa Bioactive) which is claimed to release ions in sucient quantities to
induce remineralization and inhibit secondary caries have not been thoroughly evaluated. e short-term per-
formance was disappointing with an unacceptable failure rate due to the absence of an adhesive41. (a protocol no
longer recommended by the manufacturer). Recent invitro data regarding the ion-releasing Cention n showed
its ability to neutralize the acidic environment76. However, no clinical evidence in the literature is available to
validate the laboratory data.
e quality of the interface between the tooth structure and the restoration can play a signicant role in the
occurrence of secondary caries. While not the only route for secondary caries, the presence of a defective res-
toration margin can allow acidic uids or biolm to enter the interface via gaps. However, there is currently no
agreement on the role of microleakage in the development of caries near composites. Nonetheless, some in vivo
and in vitro studies suggest that the presence of a gap next to a composite restoration can result in the formation
of a "wall lesion.". e literature also suggests the presence of a correlation between the size of the gap and the
size of the dentinal wall lesions59,64,77–79.
e results of marginal adaptation between GIC derivatives showed comparable performance with resin
composite restorations with no signicant dierence between them. Marginal adaptation of restorations is highly
dependent on the quality of the adhesive interface80,81. Traditionally, attachment of resin composite restorations
was achieved through micromechanical adhesion that involved the etching of the dental substrates82. Due to
their user-friendly application, simplied universal adhesives have grown in popularity. According to the lit-
erature, these adhesives are a single-bottle, no-mix adhesive system that works well with any adhesion strategy
and bonds adequately to tooth structure as well as various direct and indirect restorative materials83,84. However,
the simplication came at the expense of hydrophilicity which can lead to water seepage through the hybrid
layer causing nano leakage 85. erefore, dierent protocols have been suggested to improve the performance of
simplied adhesives including increasing the application time86, the addition of a hydrophobic resin layer over
the adhesive87, and application of several layers of the simplied adhesive88. ere is no clear consensus in the
literature on the optimal way to improve the long-term performance of simplied adhesives.
e results of this systematic review showed a wide variation in the adhesion protocol for the ion-releasing
materials, ranging from no pre-treatments to polyacrylic acid conditioners, ER, and SE adhesives. Nevertheless,
the overall incidence of marginal deterioration was low. It is important to highlight that the adherent substrate
which is a determining factor in the quality of the adhesion, is not consistent in all studies, with margins being
in enamel, dentine, or cementum. GICs were applied in the majority of studies aer pre-treatment with a cav-
ity conditioner of poly-acrylic acid. It has been proposed that a tooth-GIC interaction interphase layer is seen
aer GIC comes in contact with pre-treated dentin, as the pre-treatment facilitates diusion of ions into the
demineralized substrate89,90.
A recent systematic review has shown that this interphase layer is notably resistant to acidic dissolution and
hence improving the quality of the adhesive interface91. It is important to note that in this review, scores 1 and 2
of the FDI criteria in the marginal adaptation outcome were considered to be a sign of no signicant marginal
deterioration. is was done to distinguish early stages of marginal deterioration between ion-releasing materi-
als and resin composite restorations. Since, the presence of small marginal gaps, ditches could potentially be a
culprit in secondary caries development.
e risk of bias in more than 60% of the included studies was high, with only 3 studies reporting a low risk
of bias19,37,38. Performance bias was high or unclear in most studies as the nature and presentation of the used
materials are dierent and easily identied by dentists. It should be noted that the overall risk of bias of the study
was not considered as a ground for meta-analysis exclusion. erefore, the results of this analysis should be cau-
tiously interpreted. e GRADE assessment of the quality of evidence was low for both outcomes (secondary
caries and marginal adaptation) which weakens condence in the eect estimate. Consequently, the true eect
might be substantially dierent from the estimate of the eect. Imprecision and risk of bias for both outcomes
had to be downgraded by one level each. e risk of bias for 2 of the primary domains (performance bias and
selection bias) was high for studies that contributed to the weight of the analysis. e absence of events in control
and intervention arms led to a downgrading for impression by one level92.
ere are some limitations to this review. Firstly, no restriction was placed on the date of publication. Studies
that were published in the early 2000s presented a higher risk of bias and inadequate reporting which aected
their quality assessment. Although the Consolidated Standards of Reporting Trials (CONSORT) statement was
developed in 199693 and undergone a couple of revisions94,95, many clinical trial reports remained inadequate.
Furthermore, short follow-up periods resulted in an overall low number of events. Also, several new ion-releasing
materials have emerged in the last 5years. e results of this analysis were based on two broad categories of
materials (GICs and compomers). e ndings of this review cannot be applied to all commercially available
ion-releasing materials.
Conclusions
1. Within the limitation of this work, this systematic review and meta-analysis revealed that secondary caries
occurrence is not dependent on the ion-releasing capability of restorative material.
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2. Short-term follow-ups are a common denominator among the available body of evidence. Longer follow-
ups are recommended to accurately detect the performance of dierent restorative materials aer prolonged
clinical service.
3. Several new ion-releasing materials lack high-quality clinical reporting and need further investigations.
Data availability
e data used in this article are available upon request from the corresponding author.
Received: 30 April 2022; Accepted: 31 August 2022
References
1. van Dijken, J. W. & Pallesen, U. A randomized 10-year prospective follow-up of Class II nanohybrid and conventional hybrid resin
composite restorations. J. Adhes. Dent. 16, 585–592. https:// doi. org/ 10. 3290/j. jad. a33202 (2014).
2. van Dijken, J. W. & Pallesen, U. Randomized 3-year clinical evaluation of Class I and II posterior resin restorations placed with a
bulk-ll resin composite and a one-step self-etching adhesive. J. Adhes. Dent. 17, 81. https:// doi. org/ 10. 3290/j. jad. a33502 (2015).
3. Barata, J. S. et al. Inuence of gaps in adhesive restorations in the development of secondary caries lesions: An insitu evaluation.
Am. J. Dent. 25, 244–248 (2012).
4. Da Rosa Rodolpho, P. A. et al. 22-Year clinical evaluation of the performance of two posterior composites with dierent ller
characteristics. Dent. Mater. 27, 955–963. https:// doi. org/ 10. 1016/j. dental. 2011. 06. 001 (2011).
5. Kramer, N. et al. Determination of caries risk at resin composite margins. Am. J. Dent. 20, 59–64 (2007).
6. Opdam, N. J. et al. Longevity of posterior composite restorations: A systematic review and meta-analysis. J. Dent. Res. 93, 943.
https:// doi. org/ 10. 1177/ 00220 34514 544217 (2014).
7. Mjor, I. A. & Toenetti, F. Secondary caries: A literature review with case reports. Quintessence Int 31, 165–179 (2000).
8. Machiulskiene, V. et al. Terminology of dental caries and dental caries management: Consensus report of a workshop organized
by ORCA and cariology research group of IADR. Caries Res. 54, 7–14. https:// doi. org/ 10. 1159/ 00050 3309 (2020).
9. Askar, H. et al. Secondary caries: What is it, and how it can be controlled, detected, and managed?. Clin Oral Investig 24, 1869–1876.
https:// doi. org/ 10. 1007/ s00784- 020- 03268-7 (2020).
10. de Fucio, S. B. et al. Analyses of biolms accumulated on dental restorative materials. Am. J. Dent. 22, 131–136 (2009).
11. Hansel, C., Leyhausen, G., Mai, U. E. & Geurtsen, W. Eects of various resin composite (co)monomers and extracts on two caries-
associated micro-organisms invitro. J. Dent. Res. 77, 60–67. https:// doi. org/ 10. 1177/ 00220 34598 07700 10601 (1998).
12. Zalkind, M. M., Keisar, O., Ever-Hadani, P., Grinberg, R. & Sela, M. N. Accumulation of Streptococcus mutans on light-cured
composites and amalgam: An invitro study. J. Esthet. Dent. 10, 187–190. https:// doi. org/ 10. 1111/j. 1708- 8240. 1998. tb003 56.x
(1998).
13. Pires, P. M. et al. Contemporary restorative ion-releasing materials: Current status, interfacial properties and operative approaches.
Br Dent J 229, 450–458. https:// doi. org/ 10. 1038/ s41415- 020- 2169-3 (2020).
14. Lohbauer, U. Dental glass ionomer cements as permanent lling materials? – Properties. Limit. Future Trends 3, 76–96 (2010).
15. Banerjee, A. e role of glass-ionomer cements in minimum intervention (MI) caries management. In Glass-Ionomers in Dentistry
(ed. Sidhu, S. K.) 81–96 (Springer International Publishing, Cham, 2016).
16. Celik, E. U., Tunac, A. T. & Yilmaz, F. ree-year clinical evaluation of high-viscosity glass ionomer restorations in non-carious
cervical lesions: A randomised controlled split-mouth clinical trial. Clin. Oral. Investig. 23, 1473–1480. https:// doi. org/ 10. 1007/
s00784- 018- 2575-y (2019).
17. Diem, V. T., Tyas, M. J., Ngo, H. C., Phuong, L. H. & Khanh, N. D. e eect of a nano-lled resin coating on the 3-year clinical
performance of a conventional high-viscosity glass-ionomer cement. Clin. Oral Investig. 18, 753–759. https:// doi. org/ 10. 1007/
s00784- 013- 1026-z (2014).
18. Friedl, K., Hiller, K. A. & Friedl, K. H. Clinical performance of a new glass ionomer based restoration system: A retrospective
cohort study. Dent. Mater. 27, 1031–1037. https:// doi. org/ 10. 1016/j. dental. 2011. 07. 004 (2011).
19. Gurgan, S., Kutuk, Z. B., Yalcin Cakir, F. & Ergin, E. A randomized controlled 10 years follow up of a glass ionomer restorative
material in class I and class II cavities. J Dent 94, 103175. https:// doi. org/ 10. 1016/j. jdent. 2019. 07. 013 (2020).
20. Najeeb, S. et al. Modications in glass ionomer cements: Nano-sized llers and bioactive nanoceramics. Int. J. Mol. Sci. https://
doi. org/ 10. 3390/ ijms1 70711 34 (2016).
21. Salinovic, I. et al. Mechanical properties of high viscosity glass ionomer and glass hybrid restorative materials. Acta Stomatol.
Croat. 53, 125–131. https:// doi. org/ 10. 15644/ asc53/2/4 (2019).
22. Ruengrungsom, C., Palamara, J. E. A. & Burrow, M. F. Comparison of ART and conventional techniques on clinical performance
of glass-ionomer cement restorations in load bearing areas of permanent and primary dentitions: A systematic review. J. Dent. 78,
1–21. https:// doi. org/ 10. 1016/j. jdent. 2018. 07. 008 (2018).
23. Vallittu, P. K., Boccaccini, A. R., Hupa, L. & Watts, D. C. Bioactive dental materials-Do they exist and what does bioactivity mean?.
Dent. Mater. 34, 693–694. https:// doi. org/ 10. 1016/j. dental. 2018. 03. 001 (2018).
24. Garoushi, S., Vallittu, P. K. & Lassila, L. Characterization of uoride releasing restorative dental materials. Dent. Mater. J. 37,
293–300. https:// doi. org/ 10. 4012/ dmj. 2017- 161 (2018).
25. Todd, J. C. Scientic Documentation: Cention N. Ivoclar Vivadent AG, research and development. Sci. Doc. 1–58. (2016).
26. Francois, P., Fouquet, V., Attal, J. P. & Dursun, E. Commercially available uoride-releasing restorative materials: A review and a
proposal for classication. Materials (Basel) https:// doi. org/ 10. 3390/ ma131 02313 (2020).
27. Tiskaya, M., Al-eesa, N. A., Wong, F. S. L. & Hill, R. G. Characterization of the bioactivity of two commercial composites. Dent.
Mater. 35, 1757–1768. https:// doi. org/ 10. 1016/j. dental. 2019. 10. 004 (2019).
28. Glasspoole, E. A., Erickson, R. L. & Davidson, C. L. Demineralization of enamel in relation to the uoride release of materials.
Am. J. Dent. 14, 8–12 (2001).
29. Yaman, S. D., Er, O., Yetmez, M. & Karabay, G. A. Invitro inhibition of caries-like lesions with uoride-releasing materials. J. Oral
Sci. 46, 45–50. https:// doi. org/ 10. 2334/ josnu sd. 46. 45 (2004).
30. Okida, R. C., Mandarino, F., Sundfeld, R. H., de Alexandre, R. S. & Sundefeld, M. L. Invitro-evaluation of secondary caries forma-
tion around restoration. Bull. Tokyo Dent. Coll. 49, 121–128 (2008).
31. Hutton, B. et al. e PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of
health care interventions: checklist and explanations. Ann. Intern. Med. 162, 777–784. https:// doi. org/ 10. 7326/ M14- 2385 (2015).
32. Moher, D., Liberati, A., Tetzla, J., Altman, D. G. & Group, P. Preferred reporting items for systematic reviews and meta-analyses:
e PRISMA statement. PLoS Med. 6, e1000097. https:// doi. org/ 10. 1371/ journ al. pmed. 10000 97 (2009).
33. Higgins, J. P. T. et al. e Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. J. BMJ 343, d5928. https://
doi. org/ 10. 1136/ bmj. d5928 (2011).
Content courtesy of Springer Nature, terms of use apply. Rights reserved
15
Vol.:(0123456789)
Scientic Reports | (2022) 12:19244 | https://doi.org/10.1038/s41598-022-19622-6
www.nature.com/scientificreports/
34. Alonso-Coello, P. et al. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well
informed healthcare choices. 1: Introduction. BMJ 353, i2016. https:// doi. org/ 10. 1136/ bmj. i2016 (2016).
35. Guyatt, G. H. et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336,
924–926. https:// doi. org/ 10. 1136/ bmj. 39489. 470347. AD (2008).
36. Balshem, H. et al. GRADE guidelines: 3. Rating the quality of evidence. J. Clin. Epidemiol. 64, 401–406. https:// doi. org/ 10. 1016/j.
jclin epi. 2010. 07. 015 (2011).
37. Koc Vural, U., Kerimova, L. & Kiremitci, A. Clinical comparison of a micro-hybride resin-based composite and resin modied
glass ionomer in the treatment of cervical caries lesions: 36-month, split-mouth, randomized clinical trial. Odontology https:// doi.
org/ 10. 1007/ s10266- 020- 00550-8 (2020).
38. Koc Vural, U., Meral, E., Ergin, E. & Gürgan, S. Twenty-four-month clinical performance of a glass hybrid restorative in non-carious
cervical lesions of patients with bruxism: A split-mouth, randomized clinical trial. Clin. Oral Investig. 24, 1229–1238. https:// doi.
org/ 10. 1007/ s00784- 019- 02986-x (2020).
39. Balkaya, H. & Arslan, S. A two-year clinical comparison of three dierent restorative materials in class II cavities. Oper Dent. 45,
E32-e42. https:// doi. org/ 10. 2341/ 19- 078-c (2020).
40. van Dijken, J. W. & Pallesen, U. A 7-year randomized prospective study of a one-step self-etching adhesive in non-carious cervical
lesions. e eect of curing modes and restorative material. J. Dent. 40, 1060–1067. https:// doi. org/ 10. 1016/j. jdent. 2012. 08. 017
(2012).
41. van Dijken, J. W. V., Pallesen, U. & Benetti, A. A randomized controlled evaluation of posterior resin restorations of an altered
resin modied glass-ionomer cement with claimed bioactivity. Dent. Mater. 35, 335–343. https:// doi. org/ 10. 1016/j. dental. 2018.
11. 027 (2019).
42. Brackett, W. W., Dib, A., Brackett, M. G., Reyes, A. A. & Estrada, B. E. Two-year clinical performance of Class V resin-modied
glass-lonomer and resin composite restorations. Oper. Dent. 28, 477–481 (2003).
43. De Moor, R. J., Stassen, I. G., van’t Veldt, Y., Torbeyns, D. & Hommez, G. M. Two-year clinical performance of glass ionomer and
resin composite restorations in xerostomic head- and neck-irradiated cancer patients. Clin. Oral Investig. 15, 31–38. https:// doi.
org/ 10. 1007/ s00784- 009- 0355-4 (2011).
44. Gallo, J. R. et al. ree-year clinical evaluation of a compomer and a resin composite as Class V lling materials. Oper. Dent. 30,
275–281 (2005).
45. Onal, B. & Pamir, T. e two-year clinical performance of esthetic restorative materials in noncarious cervical lesions. J. Am. Dent.
Assoc. 136, 1547–1555. https:// doi. org/ 10. 14219/ jada. archi ve. 2005. 0085 (2005).
46. Türkün, L. S. & Celik, E. U. Noncarious class V lesions restored with a polyacid modied resin composite and a nanocomposite:
A two-year clinical trial. J. Adhes. Dent. 10, 399–405 (2008).
47. Wucher, M., Grobler, S. R. & Senekal, P. J. A 3-year clinical evaluation of a compomer, a composite and a compomer/composite
(sandwich) in class II restorations. Am. J. Dent. 15, 274–278 (2002).
48. Pollington, S. & van Noort, R. A clinical evaluation of a resin composite and a compomer in non-carious Class V lesions. A 3-year
follow-up. Am. J. Dent. 21, 49–52 (2008).
49. Menezes-Silva, R. et al. Randomized clinical trial of class II restoration in permanent teeth comparing ART with composite resin
aer 12months. Clin. Oral Investig. 23, 3623–3635. https:// doi. org/ 10. 1007/ s00784- 018- 2787-1 (2019).
50. Jassal, M., Mittal, S. & Tewari, S. Clinical eectiveness of a resin-modied glass ionomer cement and a mild one-step self-etch
adhesive applied actively and passively in noncarious cervical lesions: An 18-month clinical trial. Oper. Dent. 43, 581–592. https://
doi. org/ 10. 2341/ 17- 147-c (2018).
51. Miletić, I. et al. Clinical performance of a glass-hybrid system compared with a resin composite in the posterior region: Results of
a 2-year multicenter study. J. Adhes. Dent. 22, 235–247. https:// doi. org/ 10. 3290/j. jad. a44547 (2020).
52. Santiago, S. L. et al. Two-year clinical evaluation of resinous restorative systems in non-carious cervical lesions. Braz. Dent. J. 21,
229–234. https:// doi. org/ 10. 1590/ s0103- 64402 01000 03000 10 (2010).
53. Oz, F. D., Meral, E., Ergİn, E. & Gurgan, S. One-year evaluation of a new restorative glass ionomer cement for the restoration of
non-carious cervical lesions in patients with systemic diseases: A randomized, clinical trial. J. Appl. Oral Sci. 28, e20200311. https://
doi. org/ 10. 1590/ 1678- 7757- 2020- 0311 (2020).
54. Folwaczny, M., Loher, C., Mehl, A., Kunzelmann, K. H. & Hinkel, R. Tooth-colored lling materials for the restoration of cervical
lesions: A 24-month follow-up study. Oper. Dent. 25, 251–258 (2000).
55. Perdigão, J. et al. Randomized clinical trial of four adhesion strategies: 18-month results. Oper. Dent. 37, 3–11. https:// doi. org/ 10.
2341/ 11- 222-c (2012).
56. McComb, D., Erickson, R. L., Maxymiw, W. G. & Wood, R. E. A clinical comparison of glass ionomer, resin-modied glass ionomer
and resin composite restorations in the treatment of cervical caries in xerostomic head and neck radiation patients. Oper. Dent.
27, 430–437 (2002).
57. Perdigão, J., Dutra-Corrêa, M., Saraceni, S. H., Ciaramicoli, M. T. & Kiyan, V. H. Randomized clinical trial of two resin-modied
glass ionomer materials: 1-year results. Oper. Dent. 37, 591–601. https:// doi. org/ 10. 2341/ 11- 415-c (2012).
58. Demarco, F. F. et al. Should my composite restorations last forever? Why are they failing?. Braz. Oral Res. 31, e56. https:// doi. org/
10. 1590/ 1807- 3107B OR- 2017. vol31. 0056 (2017).
59. Nedeljkovic, I., Teughels, W., De Munck, J., Van Meerbeek, B. & Van Landuyt, K. L. Is secondary caries with composites a material-
based problem?. Dent. Mater. 31, e247–e277. https:// doi. org/ 10. 1016/j. dental. 2015. 09. 001 (2015).
60. Raskin, A., Setcos, J. C., Vreven, J. & Wilson, N. H. Inuence of the isolation method on the 10-year clinical behaviour of posterior
resin composite restorations. Clin. Oral Investig. 4, 148–152. https:// doi. org/ 10. 1007/ s0078 40000 069 (2000).
61. Mjor, I. A. Clinical diagnosis of recurrent caries. J. Am. Dent. Assoc. 136, 1426–1433 (2005).
62. Kuper, N. K. et al. Gap size and wall lesion development next to composite. J. Dent. Res. 93, 108S-S113. https:// doi. org/ 10. 1177/
00220 34514 534262 (2014).
63. Nedeljkovic, I. et al. Secondary caries: Prevalence, characteristics, and approach. Clin. Oral Investig. 24, 683–691. https:// doi. org/
10. 1007/ s00784- 019- 02894-0 (2020).
64. Cenci, M. S., Pereira-Cenci, T., Cury, J. A. & Ten Cate, J. M. Relationship between gap size and dentine secondary caries formation
assessed in a microcosm biolm model. Caries Res. 43, 97–102. https:// doi. org/ 10. 1159/ 00020 9341 (2009).
65. Kidd, E. A. & Fejerskov, O. What constitutes dental caries? Histopathology of carious enamel and dentin related to the action of
cariogenic biolms. J. Dent. Res. https:// doi. org/ 10. 1177/ 15440 59104 08301 s07 (2004).
66. Tjaderhane, L. et al. Strategies to prevent hydrolytic degradation of the hybrid layer-A review. Dent. Mater. 29, 999–1011. https://
doi. org/ 10. 1016/j. dental. 2013. 07. 016 (2013).
67. Toledano, M., Yamauti, M., Osorio, E. & Osorio, R. Zinc-inhibited MMP-mediated collagen degradation aer dierent dentine
demineralization procedures. Caries Res. 46, 201–207. https:// doi. org/ 10. 1159/ 00033 7315 (2012).
68. Tezvergil-Mutluay, A. et al. e requirement of zinc and calcium ions for functional MMP activity in demineralized dentin matrices.
Dent. Mater. 26, 1059–1067. https:// doi. org/ 10. 1016/j. dental. 2010. 07. 006 (2010).
69. Kuper, N. K. et al. Restoration materials and secondary caries using an invitro biolm model. J. Dent. Res. 94, 62–68. https:// doi.
org/ 10. 1177/ 00220 34514 553245 (2015).
Content courtesy of Springer Nature, terms of use apply. Rights reserved
16
Vol:.(1234567890)
Scientic Reports | (2022) 12:19244 | https://doi.org/10.1038/s41598-022-19622-6
www.nature.com/scientificreports/
70. Askar, H., Krois, J., Gostemeyer, G. & Schwendicke, F. Secondary caries risk of dierent adhesive strategies and restorative materi-
als in permanent teeth: Systematic review and network meta-analysis. J. Dent. 104, 103541. https:// doi. org/ 10. 1016/j. jdent. 2020.
103541 (2021).
71. Laske, M., Opdam, N. J. M., Bronkhorst, E. M., Braspenning, J. C. C. & Huysmans, M. Ten-year survival of class II restorations
placed by general practitioners. JDR Clin. Trans. Res. 1, 292–299. https:// doi. org/ 10. 1177/ 23800 84416 663192 (2016).
72. Opdam, N. J., Bronkhorst, E. M., Loomans, B. A. & Huysmans, M. C. 12-year survival of composite vs. amalgam restorations. J.
Dent. Res. 89, 1063–1067. https:// doi. org/ 10. 1177/ 00220 34510 376071 (2010).
73. Brouwer, F., Askar, H., Paris, S. & Schwendicke, F. Detecting secondary caries lesions: A systematic review and meta-analysis. J.
Dent. Res. 95, 143–151. https:// doi. org/ 10. 1177/ 00220 34515 611041 (2016).
74. Askar, H., Brouwer, F., Lehmensiek, M., Paris, S. & Schwendicke, F. e association between loading of restorations and secondary
caries lesions is moderated by the restoration material elasticity. J. Dent. 58, 74–79. https:// doi. org/ 10. 1016/j. jdent. 2017. 01. 002
(2017).
75. Hetrodt, F., Lausch, J., Meyer-Lueckel, H., Conrads, G. & Apel, C. Evaluation of restorative materials containing preventive addi-
tives in a secondary caries model invitro. Caries Res. 53, 447–456. https:// doi. org/ 10. 1159/ 00049 6401 (2019).
76. Gupta, N. et al. Comparison of uoride ion release and alkalizing potential of a new bulk-ll alkasite. J. Conserv. Dent. 22, 296–299.
https:// doi. org/ 10. 4103/ JCD. JCD_ 74_ 19 (2019).
77. Nassar, H. M. & Gonzalez-Cabezas, C. Eect of gap geometry on secondary caries wall lesion development. Caries Res. 45, 346–352.
https:// doi. org/ 10. 1159/ 00032 9384 (2011).
78. omas, R. Z., Ruben, J. L., ten Bosch, J. J., Fidler, V. & Huysmans, M. C. Approximal secondary caries lesion progression, a 20-week
insitu study. Caries Res. 41, 399–405. https:// doi. org/ 10. 1159/ 00010 4799 (2007).
79. Espejo, L. C., Simionato, M. R., Barroso, L. P., Netto, N. G. & Luz, M. A. Evaluation of three dierent adhesive systems using a
bacterial method to develop secondary caries invitro. Am. J. Dent. 23, 93–97 (2010).
80. Kakaboura, A., Rahiotis, C., Watts, D., Silikas, N. & Eliades, G. 3D-marginal adaptation versus setting shrinkage in light-cured
microhybrid resin composites. Dent. Mater. 23, 272–278. https:// doi. org/ 10. 1016/j. dental. 2006. 01. 020 (2007).
81. He, Z., Shimada, Y., Sadr, A., Ikeda, M. & Tagami, J. e eects of cavity size and lling method on the bonding to Class I cavities.
J. Adhes. Dent. 10, 447–453 (2008).
82. Foxton, R. M. Current perspectives on dental adhesion: (2) Concepts for operatively managing carious lesions extending into
dentine using bioactive and adhesive direct restorative materials. Jpn. Dent. Sci. Rev. 56, 208–215. https:// doi. org/ 10. 1016/j. jdsr.
2020. 08. 003 (2020).
83. Matos, A. B. et al. Bonding eciency and durability: current possibilities. Braz. Oral Res. 31, e57. https:// doi. org/ 10. 1590/ 1807-
3107B OR- 2017. vol31. 0057 (2017).
84. Alex, G. Universal adhesives: the next evolution in adhesive dentistry?. Compend. Contin. Educ. Dent. 36, 15–26 (2015).
85. Van Landuyt, K. L. et al. e role of HEMA in one-step self-etch adhesives. Dent. Mater. 24, 1412–1419. https:// doi. org/ 10. 1016/j.
dental. 2008. 02. 018 (2008).
86. Toledano, M. et al. Increases in dentin-bond strength if doubling application time of an acetone-containing one-step adhesive.
Oper. Dent. 32, 133–137. https:// doi. org/ 10. 2341/ 06- 32 (2007).
87. Sezinando, A. et al. Inuence of a hydrophobic resin coating on the immediate and 6-month dentin bonding of three universal
adhesives. Dent. Mater. 31, e236–e246. https:// doi. org/ 10. 1016/j. dental. 2015. 07. 002 (2015).
88. Chasqueira, A. F., Arantes-Oliveira, S. & Portugal, J. Eect of changes to the manufacturer application techniques on the shear
bond strength of simplied dental adhesives. J. Appl. Biomater. Funct. Mater. 11, e117–e121. https:// doi. org/ 10. 5301/ jabfm. 50001
56 (2013).
89. Toledano, M. et al. Invitro mechanical stimulation facilitates stress dissipation and sealing ability at the conventional glass ionomer
cement-dentin interface. J. Dent. 73, 61–69. https:// doi. org/ 10. 1016/j. jdent. 2018. 04. 006 (2018).
90. Yilmaz, Y., Gurbuz, T. & Kocogullari, M. E. e inuence of various conditioner agents on the interdiusion zone and microleak-
age of a glass lonomer cement with a high viscosity in primary teeth. Oper. Dent. 30, 105–112 (2005).
91. Mustafa, H. A., Soares, A. P., Paris, S., Elhennawy, K. & Zaslansky, P. e forgotten merits of GIC restorations: A systematic review.
Clin. Oral Investig. 24, 2189–2201. https:// doi. org/ 10. 1007/ s00784- 020- 03334-0 (2020).
92. Castellini, G., Bruschettini, M., Gianola, S., Gluud, C. & Moja, L. Assessing imprecision in Cochrane systematic reviews: A com-
parison of GRADE and Trial Sequential Analysis. Syst. Rev. 7, 110. https:// doi. org/ 10. 1186/ s13643- 018- 0770-1 (2018).
93. Begg, C. et al. Improving the quality of reporting of randomized controlled trials. e CONSORT statement. JAMA 276, 637–639.
https:// doi. org/ 10. 1001/ jama. 276.8. 637 (1996).
94. Moher, D., Schulz, K. F. & Altman, D. G. e CONSORT statement: revised recommendations for improving the quality of reports
of parallel-group randomised trials. Lancet 357, 1191–1194 (2001).
95. Schulz, K. F., Altman, D. G., Moher, D. & Grop, C. CONSORT 2010 Statement: updated guidelines for reporting parallel group
randomised trials. Trials 11, 32. https:// doi. org/ 10. 1186/ 1745- 6215- 11- 32 (2010).
Author contributions
Conception and design of study: H.H. H.A.M.A.M.A., S.H.M., E.A.; Acquisition of data: E.A., H.H.
H.A.M.A.M.A., H.C., M.M., S.H.M.; Analysis and/or interpretation of data: E.A., H.H. H.A.M.A.M.A.; Dra-
ing the manuscript: E.A., H.C., H.H. H.A.M.A.M.A., S.H.M.; Revising the manuscript critically for important
intellectual content: H.C., H.H. H.A.M.A.M.A., S.H.M.
Funding
is study was funded by 3M/Key Opinion Leader Scholarship.
Competing interests
e authors declare no competing interests.
Additional information
Supplementary Information e online version contains supplementary material available at https:// doi. org/
10. 1038/ s41598- 022- 19622-6.
Correspondence and requests for materials should be addressed to H.H.H.
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