Biomimetic Remineralization Strategies for Dentin Bond Stability—Systematic Review and Network Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Outcomes
2.3. Eligibility Criteria
2.4. Data Extraction and Collection
2.5. Risk of Bias Assessment
2.6. Data Synthesis and Statistical Analysis
2.6.1. Qualitative Synthesis
2.6.2. Quantitative Synthesis
- Random selection of one treatment intervention: Instead of combining interventions belonging to the same intervention category, as in the main analysis, we randomly selected only one.
- Removal of SBS test results: Instead of including all bond strength tests, as in the main analysis, we included only results from µSBS and µTBS tests.
3. Results and Discussion
3.1. Search Results
3.2. Characteristics of Included Studies
Study/Year | RoB (Score) | Study Type | ACAD | BRP | Groups | N (Teeth) | Mean (SD) | AT | OM Test | |
---|---|---|---|---|---|---|---|---|---|---|
24 h measurement | ||||||||||
ER + C | Altinci et al., 2018 [40] | M (50) | Exp. | 32% phosphoric acid | Control | Control | 9 | 35.27 (4.63) a | ER | µTBS |
F | NaF + 6 mM F | 34.7 (4.63) a | ||||||||
NaF + 24 mM F | 54.66 (4.63) a | |||||||||
NaF + 179 mM F | 47.11 (4.63) a | |||||||||
KF + 6 mM F | 51.8 (4.63) a | |||||||||
KF + 24 mM F | 48.56 (4.63) a | |||||||||
KF + 179 mM F | 47.58 (4.63) a | |||||||||
CaF2 + 6 mM F | 36.34 (4.63) a | |||||||||
CaF2 + 24 mM F | 39.49 (4.63) a | |||||||||
CaF2 + 179 mM F | 48.47 (4.63) a | |||||||||
Excite F | 48.84 (4.63) a | |||||||||
Barbosa-Martins et al. (A) 2018 [8] | M (54) | Exp. | 6% CMC | Control | Control | 6 | 26.38 (8.64) | ER | µTBS | |
F | NaF | 33.43 (10.41) | ||||||||
CaP | CPP-ACP | 45.25 (8.82) | ||||||||
Pept. | P11-4 | 46.42 (12.03) | ||||||||
Barbosa-Martins et al. (B) 2018 [7] | M (54) | Quasi-Exp. | 6% CMC | Control | Control | 6 | 21.96 (5.92) | ER | µTBS | |
F | NaF | 33.43 (10.42) | ||||||||
CaP | CPP-ACP | 45.25 (8.83) | ||||||||
Pept. | P11-4 | 46.42 (12.03) | ||||||||
Bauer et al., 2018 [29] | M (50) | Exp. | 35% phosphoric acid | Control | Control | 13 | 17 (4.1) | ER | SBS | |
CaP | 5% NbG | 17.9 (5) | ||||||||
10%NbG | 15.8 (6.4) | |||||||||
20%NbG | 16.6 (4.4) | |||||||||
40%NbG | 15.8 (4.1) | |||||||||
Cardenas et al., 2021 [30] | M (63) | Exp. | pH cycling | Control | Control | 5 | 33.74 (3.6) | Univ. | µTBS | |
F | SDF 12% | 38.03 (3.5) | ||||||||
SDF 38% | 39.68 (2.7) | |||||||||
SDF 38% without KI | 39.38 (2.5) | |||||||||
Control | Control | 34.9 (3.3) | ||||||||
F | SDF 12% | 42.45 (2.9) | ||||||||
SDF 38% | 40.47 (4.2) | |||||||||
SDF 38% without KI | 41.3 (2.5) | |||||||||
Chen et al., 2020 c | M (54) | Quasi-Exp. | pH cycling | Control | Control | 4 | 13.8 (3.35) a | Univ. | µTBS | |
CaP | Ca/P-PILP | 23.8 (3.35) a | ||||||||
Pept. | PAA-PASP | 14 (3.35) a | ||||||||
CaP | Ca/P | 11.9 (3.35) a | ||||||||
Cifuentes-Jimenez et al., 2021 [31] | M (50) | Exp. | pH cycling | Control | Control | 5 | 31.4 (4.63) a | ER | µTBS | |
F | Cariestop | 15.1 (4.63) a | ||||||||
RivaStar1 | 10.1 (4.63) a | |||||||||
RivaStar2 | 7.5 (4.63) a | |||||||||
Saforide | 23.2 (4.63) a | |||||||||
Gungormus et al., 2021 [33] | M (50) | Exp. | 37% phosphoric acid | Control | Control | 10 | 15.38 (1.3) | ER | SBS | |
CaP | NPR 60 min | 15.85 (1.44) | ||||||||
Pept. | PR 10 min | 20.81 (1.74) | ||||||||
PR 30 min | 20 (1.68) | |||||||||
PR 60 min | 16.21 (1.1) | |||||||||
Krithi et al., 2020 [34] | M (54) | Exp. | 0.5% citric acid | Control | Control | 15 | 11.83 (0.43) | ER | µSBS | |
F | NaF | 11.56 (0.15) | ||||||||
CaP | CPP-ACP | 12.12 (0.57) | ||||||||
Novamin | 11.66 (0.28) | |||||||||
Ca | Non-Fidated | 11.94 (0.27) | ||||||||
Meng et al., 2021 [35] | M (50) | Exp. | 1% citric acid | Control | Control | 8 | 46.8 b (4.63) a | Univ. | µTBS | |
Hap | Biorepair | 50.72 b (4.63) a | ||||||||
Dontodent Sensitive | 50.71 b (4.63) a | |||||||||
nHAp | 51.24 b (4.63) a | |||||||||
Control | Control | 50.41 b (4.63) a | ||||||||
Hap | Biorepair | 53.38 b (4.63) a | ||||||||
Dontodent Sensitive | 54.5 b (4.63) a | |||||||||
nHAp | 55.63 b (4.63) a | |||||||||
Control | Control | 46.85 b (4.63) a | ||||||||
Hap | Biorepair | 50.77 b (4.63) a | ||||||||
Dontodent Sensitive | 53.82 b (4.63) a | |||||||||
nHAp | 55 b (4.63) a | |||||||||
Pulidindi et al., 2021 [38] | M (63) | Exp. | 37% phosphoric acid | Control | Control | 15 | 48.84 (4.63) a | ER | µTBS | |
Pept. | P11-4 | 38.66 (4.63) a | ||||||||
CaP | CPP-ACP | 34.07 (4.63) a | ||||||||
Control | Control | 22.63 (4.63) a | ||||||||
Pept. | P11-4 | 25.37 (4.63) a | ||||||||
CaP | CPP-ACP | 23.62 (4.63) a | ||||||||
Van Duker et al., 2019 [46] | H (46) | Quasi-Exp. | 7 days in ADS | Control | Control | 10 | 23.5 (10.7) | Univ. | µTBS | |
F | SDF 38% | 19.8 (8.4) | ||||||||
SDF 38% without KI | 7.9 (6.6) | |||||||||
Yang et al., 2018 [39] | M (50) | Exp. | 1% citric acid | Control | Control | 10 | 46.5 b (4.63) a | ER | µTBS | |
CaP | CPP-ACP | 42.6 b (4.63) a | ||||||||
Novamin | 43.3 b (4.63) a | |||||||||
Control | Control | 22.3 b (4.63) a | ||||||||
CaP | CPP-ACP | 41.2 b (4.63) a | ||||||||
Novamin | 31.4 b (4.63) a | |||||||||
ER + B | Barbosa-Martins et al. (B) 2018 | M (54) | Quasi-Exp. | BHI+ S.Mutans | Control | Control | 6 | 22.89 (2.68) | ER | µTBS |
F | NaF | 26.94 (6.7) | ||||||||
CaP | CPP-ACP | 47.95 (6.69) | ||||||||
Pept. | P11-4 | 42.07 (7.83) | ||||||||
Dávila-Sánchez et al., 2020 [32] | M (54) | Exp. | Cariogenic + S. Mutans | Control | Control | 7 | 14.42 (4.43) | Univ. | µTBS | |
Fls. | QUE | 24.58 (4.9) | ||||||||
HES | 18.41 (5.3) | |||||||||
RUT | 26 (5.51) | |||||||||
NAR | 24.64 (3.7) | |||||||||
PRO | 20.66 (3.92) | |||||||||
de Sousa et al., 2019 [44] | M (50) | Quasi-Exp. | Cariogenic + S. Mutans | Control | Control | 8 | 21.07 (3.24) | ER | µTBS | |
Pept. | P11-4 | 42.07 (7.83) | ||||||||
Moreira et al., 2021 [15] | M (54) | Exp. | Cariogenic + S. Mutans | Control | Control | 8 | 25.4 (2.45) | ER | µTBS | |
F | NaF | 25.47 (4.8) | ||||||||
CaP | CPP-ACP | 41.79 (5.85) | ||||||||
Pept. | P11-4 | 40.12 (3.62) | ||||||||
Siqueira et al., 2020 [37] | M (63) | Exp. | Cariogenic + S. Mutans | Control | Control | 5 | 16.81 (3.5) | Univ. | µTBS | |
F | SDF 12% | 21.11 (4.1) | ||||||||
SDF 38% | 24.36 (3.4) | |||||||||
Control | Control | 19.89 (2.4) | ||||||||
F | SDF 12% | 24.47 (3.4) | ||||||||
SDF 38% | 26.32 (2) | |||||||||
SE + C | Atomura et al., 2018 [43] | H (46) | Quasi-Exp. | 7 days in ADS | Control | Control | unknown | 48.3 (13) | SE | µTBS |
F | NaF | 47.7 (8.6) | ||||||||
FCP complex | 43.9 (14.3) | |||||||||
Barbosa-Martins et al. (A) 2018 [8] | M (54) | Exp. | 48 h 6% CMC | Control | Control | 6 | 25.38 (8.58) | SE | µTBS | |
F | NaF | 35.59 (9.18) | ||||||||
CaP | CPP-ACP | 48.11 (11.71) | ||||||||
Pept. | P11-4 | 25.7 (8.95) | ||||||||
Cardenas et al., 2021 [30] | M (63) | Exp. | pH cycling | Control | Control | 5 | 33.74 (3.6) | Univ. | µTBS | |
F | SDF 12% | 39.53 (4.2) | ||||||||
SDF 38% | 41.31 (2) | |||||||||
SDF 38% without KI | 40.55 (2.9) | |||||||||
Control | Control | 36.56 (4.1) | ||||||||
F | SDF 12% | 39.98 (1.7) | ||||||||
SDF 38% | 41.08 (3) | |||||||||
SDF 38% without KI | 41.57 (2.4) | |||||||||
Chen et al., 2020 [14] | M (54) | Quasi-Exp. | pH cycling | Control | Control | 4 | 13.8 (3.35) a | Univ. | µTBS | |
CaP | Ca/P-PILP | 23.8 (3.35) a | ||||||||
Pept. | PAA-PASP | 14 (3.35) a | ||||||||
CaP | Ca/P | 11.9 (3.35) a | ||||||||
Control | Control | 9.2 (3.35) a | ||||||||
CaP | Ca/P-PILP | 15.1 (3.35) a | ||||||||
Pept. | PAA-PASP | 9.3 (3.35) a | ||||||||
CaP | Ca/P | 9.8 (3.35) a | ||||||||
Cifuentes-Jimenez et al., 2021 [31] | M (50) | Exp. | pH cycling | Control | Control | 5 | 31.4 (3.35) a | SE | µTBS | |
F | Cariestop | 9.6 (3.35) a | ||||||||
Saforide | 8.03 (3.35) a | |||||||||
Gungormus et al., 2021 [33] | M (50) | Exp. | 37% phosphoric acid | Control | Control | 10 | 15.38 (1.3) | SE | SBS | |
CaP | NPR 60 min | 15.49 (1.17) | ||||||||
Pept. | PR 10 min | 18.93 (0.99) | ||||||||
PR 30 min | 19.62 (0.9) | |||||||||
PR 60 min | 21.73 (1.57) | |||||||||
Krithi et al., 2020 [34] | M (54) | Exp. | 0.5% citric acid | Control | Control | 15 | 11.83 (0.43) | SE | µSBS | |
F | NaF | 12.4 (0.18) | ||||||||
CaP | CPP-ACP | 11.97 (0.39) | ||||||||
Novamin | 11.97 (0.17) | |||||||||
Ca | Non-Fidated | 10.62 (0.11) | ||||||||
Meng et al., 2021 [35] | M (50) | Exp. | 1% citric acid | Control | Control | 8 | 46.8 b (3.35) a | Univ. | µTBS | |
Hap | Biorepair | 47.62 b (3.35) a | ||||||||
Dontodent Sensitive | 51.89 b (3.35) a | |||||||||
nHAp | 51.89 b (3.35) a | |||||||||
Control | Control | 56.3 b (3.35) a | ||||||||
Hap | Biorepair | 51.62 b (3.35) a | ||||||||
Dontodent Sensitive | 57.47 b (3.35) a | |||||||||
nHAp | 58.39 b (3.35) a | |||||||||
Control | Control | 56.8 b (3.35) a | ||||||||
Hap | Biorepair | 52.25 b (3.35) a | ||||||||
Dontodent Sensitive | 50.8 b (3.35) a | |||||||||
nHAp | 56.1 b (3.35) a | |||||||||
Paik et al., 2022 [42] | M (50) | Exp. | 35% phosphoric acid | Control | Control | 4 | 21.66 (3.35) a | Univ. | µTBS | |
Fls. | ICT | 24.4 (3.35) a | ||||||||
FIS | 26.81 (3.35) a | |||||||||
SIB | 25.65 (3.35) a | |||||||||
CPIC | 25.97 (3.35) a | |||||||||
ICT + C | 30.63 (3.35) a | |||||||||
FIS + C | 25.63 (3.35) a | |||||||||
SIB + C | 24.76 (3.35) a | |||||||||
Pei et al., 2019 [36] | M (50) | Exp. | 1% citric acid | Control | Control | 4 | 43.61 (3.35) a | SE | µTBS | |
Hap | Biorepair | 33.16 (3.35) a | ||||||||
Dontodent Sensit. | 35.41 (3.35) a | |||||||||
nHAp | 46.92 (3.35) a | |||||||||
Control | Control | 47.47 (3.35) a | ||||||||
Hap | Biorepair | 43.47 (3.35) a | ||||||||
Dontodent Sensit. | 42.3 (3.35) a | |||||||||
nHAp | 41.24 (3.35) a | |||||||||
Priya et al., 2020 [45] | H (46) | Quasi-Exp. | 37% phosphoric acid | Control | Control | 13 | 6.677 (1.254) | Univ. | SBS | |
F | VivaSens | 3.332 (0.78) | ||||||||
MS Coat F | 3.127 (0.478) | |||||||||
HEMA | GLUMA Desensit. | 4.572 (0.718) | ||||||||
Systemp | 9.697 (1.127) | |||||||||
Zang et al., 2018 [41] | M (50) | Exp. | 37% phosphoric acid | Control | Control | 6 | 19.73 b (2.108) | Univ. | SBS | |
SiO2 | Charged mesoporous | 20.57 b (2.244) | ||||||||
Zumstein et al., 2018 [47] | M (50) | Quasi-Exp. | pH cycling | Control | Control | 20 | 24.7 (8.1) c | SE | µTBS | |
F | SnCl2/AmF4 | 23.3 (8.2) c | ||||||||
Control | Control | 23.73 (8) c | Univ. | |||||||
F | SnCl2/AmF4 | 21.39 (6.8) c | ||||||||
SE + B | Siqueira et al., 2020 [37] | M (63) | Exp. | Cariogenic + S. Mutans | Control | Control | 5 | 16.81 (3.5) | Univ. | µTBS |
F | SDF 12% | 20.02 (4.6) | ||||||||
SDF 38% | 25.21 (3) | |||||||||
Control | Control | 19.61 (3.3) | ||||||||
F | SDF 12% | 23.82 (4.4) | ||||||||
SDF 38% | 27.16 (3.6) | |||||||||
TMC measurement | ||||||||||
ER + C | Pulidindi et al., 2021 [38] | M (63) | Exp. | 37% phosphoric acid | Control | Control | 15 | 48.84 (4.63) a | ER | µTBS |
Pept. | P11-4 | 25.37 (4.63) a | ||||||||
CaP | CPP-ACP | 23.62 (4.63) a | ||||||||
ER + B | Dávila-Sánchez et al., 2020 [32] | M (54) | Exp. | Cariogenic + S. Mutans | Control | Control | 7 | 14.42 (4.43) | Univ. | µTBS |
Fls. | QUE | 12.02 (5.21) | ||||||||
HES | 15.73 (6.07) | |||||||||
RUT | 21.08 (4.75) | |||||||||
NAR | 22.12 (2.92) | |||||||||
PRO | 17.2 (2.72) | |||||||||
SE + C | Chen et al., 2020 [14] | M (54) | Quasi-Exp. | pH cycling | Control | Control | 4 | 13.8 (3.35) a | Univ. | µTBS |
CaP | Ca/P-PILP | 15.1 (3.35) a | ||||||||
Pept. | PAA-PASP | 9.3 (3.35) a | ||||||||
CaP | Ca/P | 9.8 (3.35) a | ||||||||
Paik et al., 2022 [42] | M (50) | Exp. | 35% phosphoric acid | Control | Control | 4 | 21.66 (3.35) a | Univ. | µTBS | |
Fls. | ICT | 20.53 (3.35) a | ||||||||
FIS | 19.4 (3.35) a | |||||||||
SIB | 22.04 (3.35) a | |||||||||
CPIC | 23.43 (3.35) a | |||||||||
ICT + C | 26.74 (3.35) a | |||||||||
FIS + C | 23.42 (3.35) a | |||||||||
SIB + C | 25.17 (3.35) a | |||||||||
Storage in a fluid solution for 3-month measurement | ||||||||||
ER + C | Bauer et al., 2018 [29] | M (50) | Exp. | 35% phosphoric acid | Control | Control | 13 | 17 (4.1) | ER | SBS |
CaP | 5% NbG | 11.8 (3.7) | ||||||||
10%NbG | 13.9 (3.2) | |||||||||
20%NbG | 13.2 (2.7) | |||||||||
40%NbG | 14.7 (2.9) | |||||||||
SE + C | Atomura et al., 2018 [43] | H (46) | Quasi-Exp. | 7 days in ADS | Control | Control | unknown | 48.3 (13) | SE | µTBS |
F | NaF | 42.6 (12.1) | ||||||||
FCP complex | 47.4 (9.2) | |||||||||
Storage in a fluid solution for 6-month measurement | ||||||||||
ER + C | Altinci et al., 2018 [40] | M (50) | Exp. | 32% phosphoric acid | Control | Control | 9 | 35.27 (4.63) a | ER | µTBS |
F | NaF + 6 mM F | 50.31 (4.63) a | ||||||||
NaF + 24 mM F | 49.28 (4.63) a | |||||||||
NaF+179 mM F | 47.73 (4.63) a | |||||||||
KF + 6 mM F | 41.95 (4.63) a | |||||||||
KF + 24 mM F | 51.53 (4.63) a | |||||||||
KF + 179 mM F | 54.29 (4.63) a | |||||||||
CaF2 + 6 mM F | 52.25 (4.63) a | |||||||||
CaF2+24 mM F | 41.1 (4.63) a | |||||||||
CaF2+179 mM F | 40.85 (4.63) a | |||||||||
Excite F | 46.22 (4.63) a | |||||||||
de Sousa et al., 2019 [44] | M (50) | Quasi-Exp. | Cariogenic + S. Mutans | Control | Control | 8 | 21.07 (3.24) | ER | µTBS | |
Pept. | P11-4 | 31.98 (3.44) | ||||||||
Moreira et al., 2021 [15] | M (54) | Exp. | Cariogenic + S. Mutans | Control | Control | 8 | 25.4 (2.45) | ER | µTBS | |
F | NaF | 18.36 (5.5) | ||||||||
CaP | CPP-ACP | 36.55 (4.27) | ||||||||
Storage in a fluid solution for 12-month measurement | ||||||||||
ER + C | Altinci et al., 2018 [40] | M (50) | Exp. | 32% phosphoric acid | Control | Control | 9 | 35.27 (4.63) a | ER | µTBS |
F | NaF + 6 mM F | 51.63 (4.63) a | ||||||||
NaF + 24 mM F | 45.56 (4.63) a | |||||||||
NaF + 179 mM F | 39.31 (4.63) a | |||||||||
KF + 6 mM F | 40.01 (4.63) a | |||||||||
KF + 24 mM F | 51.85 (4.63) a | |||||||||
KF + 179 mM F | 36.48 (4.63) a | |||||||||
CaF2 + 6 mM F | 33.06 (4.63) a | |||||||||
CaF2 + 24 mM F | 38.24 (4.63) a | |||||||||
CaF2 + 179 mM F | 0.88 (4.63) a | |||||||||
Excite F | 42.4 (4.63) a | |||||||||
Yang et al., 2018 [39] | M (50) | Exp. | 1% citric acid | Control | Control | 10 | 46.5 b (4.63) a | ER | µTBS | |
CaP | CPP-ACP | 41.2 b (4.63) a | ||||||||
Novamin | 31.4 b (4.63) a | |||||||||
SE + C | Zumstein et al., 2018 [51] | M (50) | Quasi-Exp. | pH cycling | Control | Control | 20 | 24.7 (8.1) c | SE | µTBS |
F | SnCl2/AmF4 | 16.3 (6.36) c | ||||||||
Control | Control | 15.43 (6.53) c | Univ. | |||||||
F | SnCl2/AmF4 | 14.12 (7.12) c | ||||||||
Storage in a fluid solution for 18-month measurement | ||||||||||
ER + B | Moreira et al., 2021 [15] | M (54) | Exp. | Cariogenic + S. Mutans | Control | Control | 8 | 25.4 (2.45) | ER | µTBS |
F | NaF | 7.81 (4.48) | ||||||||
CaP | CPP-ACP | 26.01 (3.28) | ||||||||
Pept. | P11-4 | 25.24 (3.98) |
3.3. Meta-Regressions
3.3.1. Influence of the Adhesive Technique on NMA Effect Estimates
3.3.2. Influence of the ACAD Protocol on NMA Effect Estimates
3.4. Network Meta-Analysis
3.4.1. ER Technique with Chemical ACAD Protocol
3.4.2. ER Technique with Biological ACAD Protocol
3.4.3. SE Technique with Chemical ACAD Protocol
3.5. NMA Confidence Ratings
3.5.1. ER Technique with Chemical ACAD Protocol
3.5.2. ER Technique with Biological ACAD Protocol
3.5.3. SE Technique with Chemical ACAD Protocol
3.6. Rankings
3.6.1. ER Technique with Chemical ACAD Protocol
3.6.2. ER Technique with Biological ACAD Protocol
3.6.3. SE Technique with Chemical ACAD Protocol
3.7. Sensitivity Analyses
3.7.1. ER Technique with Chemical ACAD Protocol
3.7.2. ER Technique with Biological ACAD Protocol
3.7.3. SE Technique with Chemical ACAD Protocol
3.8. Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
NMA | Network meta-analysis |
ACAD | Artificial caries-affected dentin |
BR | Biomimetic remineralization |
Appendix A
Appendix A.1. Search Strategies
Studies | Reason for Exclusion |
---|---|
Doozandeh et al. (2015) [57] | 1—Without ACAD |
Bergamin et al. (2016 )[58] | 1—Without ACAD |
Ghani et al. (2017) [59] | 1—Without ACAD |
Komori et al. (2009) [60] | 1—Without ACAD |
Leal et al. (2017) [61] | 1—Without ACAD |
Luong et al. (2020) [62] | 1—Without ACAD |
Meraji et al. (2018) [63] | 1—Without ACAD |
Prasansuttiporn et al. (2020) [64] | 1—Without ACAD |
Sajjad et al. (2022) [65] | 1—Without ACAD |
Yilmaz et al. (2017) [66] | 1—Without ACAD |
Castellan et al. (2010) [67] | 2—Without remineralization procedures |
Okuyama et al. (2011) [68] | 2—Without remineralization procedures |
Wang et al. (2012) [69] | 2—Without remineralization procedures |
de-Melo et al. (2013) [70] | 2—Without remineralization procedures |
Carvalho et al. (2016) [71] | 2—Without remineralization procedures |
Deari et al. (2017) [72] | 2—Without remineralization procedures |
Giacomini et al. (2017) [73] | 2—Without remineralization procedures |
Rodrigues et al. (2017) [74] | 2—Without remineralization procedures |
Imiolczyk et al. (2017) [75] | 2—Without remineralization procedures |
Stape et al. (2021) [76] | 2—Without remineralization procedures |
Hartz et al. (2022) [77] | 2—Without remineralization procedures |
Wang et al. (2016) [78] | 3—Modified Materials |
Moda et al. (2018) [79] | 3—Modified Materials |
Choi et al. (2020) [80] | 3—Modified Materials |
Abdelshafi et al. (2021) [81] | 3—Modified Materials |
Al-Qahtani et al. (2021) [82] | 3—Modified Materials |
Khor et al. (2022) [83] | 3—Modified Materials |
Adebayo et al. (2010) [84] | 4—Without bond strength measurement |
Liu et al. (2011) [85] | 4—Without bond strength measurement |
Chen et al. (2016) [86] | 4—Without bond strength measurement |
Bortolotto et al. (2017) [87] | 4—Without bond strength measurement |
Liang et al. (2017) [88] | 4—Without bond strength measurement |
Wang et al. (2021) [89] | 4—Without bond strength measurement |
Zhou et al. (2016) [90] | 5—Modified adhesive |
Flury et al. (2017) [91] | 5—Modified adhesive |
Ye et al. (2017) [92] | 5—Modified adhesive |
Liang et al. (2018) [93] | 5—Modified adhesive |
Cardenas et al. (2021) [48] | 5—Modified adhesive |
Hasegawa et al. (2021) [94] | 5—Modified adhesive |
Bridi et al. (2012) [95] | 6—Not biomimetic remineralization agents |
Castellan et al. (2013) [96] | 6—Not biomimetic remineralization agents |
Monteiro et al. (2013) [97] | 6—Not biomimetic remineralization agents |
Abu Nawareg et al. (2016) [98] | 6—Not biomimetic remineralization agents |
Lee et al. (2017) [99] | 6—Not biomimetic remineralization agents |
Prasansuttiporn et al. (2017) [100] | 6—Not biomimetic remineralization agents |
Ramezanian Nik et al. (2017) [101] | 6—Not biomimetic remineralization agents |
Costa et al. (2019) [102] | 6—Not biomimetic remineralization agents |
Fialho et al. (2019) [103] | 6—Not biomimetic remineralization agents |
Landmayer et al. (2020) [104] | 6—Not biomimetic remineralization agents |
Costa et al. (2021) [105] | 6—Not biomimetic remineralization agents |
Giacomini et al. (2021) [106] | 6—Not biomimetic remineralization agents |
Shioya et al. (2021) [107] | 6—Not biomimetic remineralization agents |
Xu et al. (2021) [108] | 6—Not biomimetic remineralization agents |
Atay et al. (2022) [109] | 6—Not biomimetic remineralization agents |
Lemos et al. (2022) [110] | 6—Not biomimetic remineralization agents |
Zhang et al. (2015) [111] | 7—Non-Roman Alphabet language after unsuccessful contact with authors |
Wang et al. (2017) [112] | 7—Non-Roman Alphabet language after unsuccessful contact with authors |
Meng et al. (2022) [113] | 7—Non-Roman Alphabet language after unsuccessful contact with authors |
Kim et al. (2020) [13] | 8—Missing control group |
Study | Reason for Exclusion |
---|---|
Atomura et al. (2018) [43] | Standard deviation and sample size (N) missing and authors did not respond to emails. |
Study | Data Information |
---|---|
Zumstein et al. (2018) [50] | Missing data obtained from another meta-analysis by Wiegand et al., 2021 [57]. Authors did not respond to emails. |
Study | Data Information |
---|---|
Barbosa-Martins et al. (A) (2018) [8] | Unit of statistical analysis |
Barbosa-Martins et al. (B) (2018) [7] | Unit of statistical analysis |
de Sousa et al. (2019) [44] | Unit of statistical analysis |
Moreira et al. (2021) [15] | Unit of statistical analysis |
Meng et al. (2021) [35] | Mean and SD values |
Pei et al. (2019) [36] | Unit of statistical analysis |
Pulidindi et al. (2021) [38] | Unit of statistical analysis |
Yang et al. (2018) [39] | Mean and SD values and unit of statistical analysis |
Zang et al. (2018) [41] | Mean and SD values and unit of statistical analysis |
Appendix A.2. OpenBUGS Code for Random Effects Meta-Regression Model with a Subgroup Indicator Covariate
Appendix A.3. Meta-Regression
NMA Comparison | Mean | 95% CrI |
---|---|---|
CTRL:F | 0.8846 | (−1.72; 3.52) |
CTRL:CaP | −3.351 | (−6.664; −0.03009) |
CTRL:Pept. | −5.384 | (−9.103; −1.65) |
CTRL:SiO2 | −0.8296 | (−10.72; 9.049) |
CTRL:HEMA | −1.728 | (−10.22; 6.768) |
CTRL:FLs | −4.982 | (−12.35; 2.382) |
CTRL:Ca | 0.3152 | (−5.575; 6.211) |
CTRL:HAp | 1.223 | (−2.536; 4.98) |
F:CaP | −4.236 | (−7.499; −0.9842) |
F:Pept. | −6.268 | (−9.996; −2.552) |
F:SiO2 | −1.714 | (−11.95; 8.521) |
F:HEMA | −2.613 | (−11.1; 5.868) |
F:FLs | −5.867 | (−13.45; 1.726) |
F:Ca | −0.5694 | (−6.352; 5.196) |
F:HAp | 0.3381 | (−3.942; 4.631) |
CaP:Pept. | −2.032 | (−5.601; 1.525) |
CaP:SiO2 | 2.522 | (−7.906; 12.94) |
CaP:HEMA | 1.623 | (−7.297; 10.54) |
CaP:FLs | −1.631 | (−9.428; 6.172) |
CaP:Ca | 3.666 | (−2.196; 9.529) |
CaP:HAp | 4.574 | (−0.07638; 9.248) |
Pept.:SiO2 | 4.554 | (−6.013; 15.1) |
Pept.:HEMA | 3.656 | (−5.425; 12.76) |
Pept.:FLs | 0.4015 | (−7.578; 8.394) |
Pept.:Ca | 5.699 | (−0.6984; 12.08) |
Pept.:HAp | 6.606 | (1.658; 11.56) |
SiO2:HEMA | −0.8984 | (−13.94; 12.13) |
SiO2:FLs | −4.153 | (−16.46; 8.18) |
SiO2:Ca | 1.145 | (−10.37; 12.64) |
SiO2:HAp | 2.052 | (−8.496; 12.66) |
HEMA:FLs | −3.254 | (−14.41; 7.904) |
HEMA:Ca | 2.043 | (−8.051; 12.17) |
HEMA:HAp | 2.951 | (−6.264; 12.18) |
FLs:Ca | 5.297 | (−3.932; 14.52) |
FLs:HAp | 6.205 | (−1.944; 14.31) |
Ca:HAp | 0.9075 | (−5.872; 7.675) |
NMA Comparison | Mean | 95% CrI |
---|---|---|
CTRL:F | −7.588 | (−11.3; −3.877) |
CTRL:CaP | −12.97 | (−17.32; −8.628) |
CTRL:Pept. | −14.2 | (−18.64; −9.77) |
CTRL:SiO2 | −10.15 | (−20.78; 0.5214) |
CTRL:HEMA | −10.62 | (−19.71; −1.499) |
CTRL:FLs | −11.2 | (−18.69; −3.706) |
CTRL:Ca | −9.321 | (−15.94; −2.717) |
CTRL:HAp | −9.208 | (−14.65; −3.78) |
F:CaP | −5.381 | (−8.621; −2.139) |
F:Pept. | −6.617 | (−10.3; −2.935) |
F:SiO2 | −2.563 | (−12.68; 7.6) |
F:HEMA | −3.031 | (−11.43; 5.39) |
F:FLs | −3.61 | (−11.2; 3.981) |
F:Ca | −1.734 | (−7.48; 3.999) |
F:HAp | −1.62 | (−5.972; 2.749) |
CaP:Pept. | −1.236 | (−4.793; 2.332) |
CaP:SiO2 | 2.818 | (−7.433; 13.12) |
CaP:HEMA | 2.35 | (−6.401; 11.14) |
CaP:FLs | 1.77 | (−6.08; 9.585) |
CaP:Ca | 3.647 | (−2.149; 9.428) |
CaP:HAp | 3.761 | (−0.8584; 8.391) |
Pept.:SiO2 | 4.055 | (−6.382; 14.52) |
Pept.:HEMA | 3.586 | (−5.386; 12.55) |
Pept.:FLs | 3.007 | (−4.964; 10.97) |
Pept.:Ca | 4.884 | (−1.454; 11.21) |
Pept.:HAp | 4.997 | (−0.001725; 10.01) |
SiO2:HEMA | −0.4682 | (−13.38; 12.48) |
SiO2:FLs | −1.048 | (−13.4; 11.32) |
SiO2:Ca | 0.829 | (−10.56; 12.18) |
SiO2:HAp | 0.9427 | (−9.562; 11.42) |
HEMA:FLs | −0.5796 | (−11.75; 10.58) |
HEMA:Ca | 1.297 | (−8.708; 11.3) |
HEMA:HAp | 1.411 | (−7.759; 10.56) |
FLs:Ca | 1.877 | (−7.369; 11.12) |
FLs:HAp | 1.991 | (−6.31; 10.31) |
Ca:HAp | 0.1137 | (−6.606; 6.846) |
Appendix A.4. Contribution Tables
NMA Treatment Effect/Comparisons | Ca:CaP | Ca:CTRL | Ca:F | CaP:CTRL | CaP:F | CaP:Pept. | CTRL:F | CTRL:HAp | CTRL:Pept. | F:Pept. |
---|---|---|---|---|---|---|---|---|---|---|
Mixed estimates | ||||||||||
CaP:CTRL | 2.935 | 2.375 | 0.56 | 63.32 | 7.4 | 7.4783 | 8.4533 | 0 | 6.985 | 0.4933 |
CaP:F | 4.195 | 0.0675 | 4.2625 | 22.975 | 31.11 | 6.1242 | 25.1317 | 0 | 2.2242 | 3.9 |
CaP:Pept. | 1.1317 | 0.6967 | 0.435 | 16.795 | 5.04 | 52.39 | 0.535 | 0 | 18.0267 | 4.94 |
Ca:CaP | 38.27 | 15.92 | 11.94 | 17.4467 | 7.655 | 2.7583 | 3.2517 | 0 | 1.725 | 1.0333 |
Ca:CTRL | 15.095 | 36.58 | 15.3917 | 13.445 | 0.125 | 1.775 | 14.73 | 0 | 2.3117 | 0.5367 |
Ca:F | 12.5817 | 15.78 | 38.56 | 3.1633 | 7.905 | 1.5133 | 18.9033 | 0 | 0.04 | 1.5533 |
CTRL:F | 0.5775 | 2.515 | 3.0925 | 8.505 | 8.155 | 0.2275 | 70.38 | 0 | 3.3875 | 3.16 |
CTRL:HAp | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 100 | 0 | 0 |
CTRL:Pept. | 0.8633 | 0.8783 | 0.015 | 14.86 | 1.5317 | 17.255 | 7.2017 | 0 | 51.7 | 5.685 |
F:Pept. | 1.5167 | 0.5925 | 2.1092 | 3.9225 | 10.465 | 15.9042 | 25.565 | 0 | 22.235 | 17.69 |
Indirect estimates | ||||||||||
CaP:HAp | 2.0033 | 1.5833 | 0.42 | 31.66 | 4.9333 | 5.0267 | 5.7233 | 43.6233 | 4.6567 | 0.37 |
Ca:HAp | 10.2008 | 18.29 | 10.3225 | 8.9633 | 0.1 | 1.3375 | 9.82 | 38.8133 | 1.74 | 0.4025 |
Ca:Pept. | 17.22 | 16.965 | 12.4708 | 0.7075 | 1.7067 | 19.6342 | 4.2742 | 0 | 20.5317 | 6.49 |
F:HAp | 0.4445 | 1.6767 | 2.1212 | 5.6992 | 5.4367 | 0.182 | 35.19 | 44.8545 | 2.2887 | 2.1067 |
HAp:Pept. | 0.6475 | 0.6595 | 0.012 | 9.9067 | 1.1495 | 11.7037 | 4.9275 | 41.3437 | 25.85 | 3.79 |
NMA Treatment Effect/Comparisons | CaP:CTRL | CaP:F | CaP:Pept. | CTRL:FLs | CTRL:F | CTRL:Pept. | F:Pept. |
---|---|---|---|---|---|---|---|
Mixed estimates | |||||||
CaP:CTRL | 47.08 | 13.7 | 12.3317 | 0 | 14.5567 | 11.475 | 0.8567 |
CaP:F | 17.525 | 40.42 | 11.1833 | 0 | 19.6783 | 2.1533 | 9.03 |
CaP:Pept. | 16.035 | 11.5217 | 43.84 | 0 | 1.0367 | 17.0717 | 10.485 |
CTRL:FLs | 0 | 0 | 0 | 100 | 0 | 0 | 0 |
CTRL:F | 6.015 | 6.345 | 0.33 | 0 | 71.49 | 8.075 | 7.745 |
CTRL:Pept. | 7.505 | 1.1033 | 8.6083 | 0 | 12.8783 | 58.13 | 11.775 |
F:Pept. | 0.9933 | 8.17 | 9.1633 | 0 | 21.8183 | 20.825 | 39.04 |
Indirect estimates | |||||||
CaP:FLs | 23.54 | 9.1333 | 8.2925 | 40.9658 | 9.7758 | 7.65 | 0.6425 |
FLs:F | 4.01 | 4.2575 | 0.2475 | 45.1658 | 35.745 | 5.4108 | 5.1633 |
FLs:Pept. | 5.0033 | 0.8275 | 5.8308 | 42.7458 | 8.6775 | 29.065 | 7.85 |
NMA Treatment Effect/Comparisons | Ca:CaP | Ca:CTRL | Ca:F | CaP:CTRL | CaP:F | CaP:Pept. | CTRL: FLS | CTRL:F | CTRL: HEMA | CTRL:HAp | CTRL:Pept. | CTRL:SiO2 | F:HEMA | F:Pept. |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mixed estimates | ||||||||||||||
CaP:CTRL | 5.215 | 3.955 | 1.26 | 51.94 | 9.345 | 8.4575 | 0 | 10.425 | 0.4725 | 0 | 8.165 | 0 | 0.4725 | 0.2925 |
CaP:F | 6.4433 | 0.7333 | 5.71 | 20.78 | 29.56 | 5.3175 | 0 | 23.9333 | 1.1025 | 0 | 3.5225 | 0 | 1.1025 | 1.795 |
CaP:Pept. | 1.9783 | 1.3433 | 0.635 | 14.09 | 4.5933 | 54.07 | 0 | 2.3683 | 0.13 | 0 | 17.932 | 0 | 0.13 | 2.73 |
Ca:CaP | 41.85 | 14.96 | 11.2705 | 15.37 | 8.04 | 2.8205 | 0 | 2.5325 | 0.168 | 0 | 2.2905 | 0 | 0.168 | 0.53 |
Ca:CTRL | 13.2408 | 37.83 | 16.005 | 10.395 | 0.6525 | 2.1933 | 0 | 15.825 | 0.6925 | 0 | 2.3333 | 0 | 0.6925 | 0.14 |
Ca:F | 11.2397 | 16.065 | 39.64 | 3.365 | 6.74 | 1.1347 | 0 | 19.125 | 0.773 | 0 | 0.468 | 0 | 0.773 | 0.6667 |
CTRL:FLs | 0 | 0 | 0 | 0 | 0 | 0 | 100 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
CTRL:F | 0.4375 | 2.85 | 3.2875 | 5.19 | 5.3533 | 0.6008 | 0 | 72.96 | 3.15 | 0 | 1.8108 | 0 | 3.15 | 1.21 |
CTRL:HEMA | 0.174 | 0.9567 | 1.1307 | 1.74 | 1.8025 | 0.2365 | 0 | 18.35 | 52.86 | 0 | 0.6432 | 0 | 21.6898 | 0.4067 |
CTRL:HAp | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 100 | 0 | 0 | 0 | 0 |
CTRL:Pept. | 1.553 | 1.29 | 0.263 | 11.88 | 2.5467 | 15.9797 | 0 | 5.8717 | 0.248 | 0 | 56.8 | 0 | 0.248 | 3.31 |
CTRL:SiO2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 100 | 0 | 0 |
F:HEMA | 0.174 | 0.9433 | 1.1173 | 1.72 | 1.78 | 0.234 | 0 | 18.125 | 21.4223 | 0 | 0.634 | 0 | 53.44 | 0.4 |
F:Pept. | 2.31 | 0.455 | 2.765 | 3.8833 | 9.255 | 15.4483 | 0 | 28.2333 | 1.265 | 0 | 26.07 | 0 | 1.265 | 9.05 |
Indirect estimates | ||||||||||||||
CaP:FLs | 3.5907 | 2.6367 | 0.954 | 25.97 | 6.23 | 5.6773 | 41.468 | 7.04 | 0.378 | 0 | 5.4433 | 0 | 0.378 | 0.234 |
CaP:HEMA | 4.1842 | 1.6142 | 2.57 | 23.36 | 12.08 | 4.2917 | 0 | 3.6925 | 24.7767 | 0 | 3.495 | 0 | 19.1392 | 0.7967 |
CaP:HAp | 3.5907 | 2.6367 | 0.954 | 25.97 | 6.23 | 5.6773 | 0 | 7.04 | 0.378 | 41.468 | 5.4433 | 0 | 0.378 | 0.234 |
CaP:SiO2 | 3.5907 | 2.6367 | 0.954 | 25.97 | 6.23 | 5.6773 | 0 | 7.04 | 0.378 | 0 | 5.4433 | 41.468 | 0.378 | 0.234 |
Ca:FLs | 9.097 | 18.915 | 10.685 | 6.93 | 0.522 | 1.645 | 38.697 | 10.55 | 0.552 | 0 | 1.75 | 0 | 0.552 | 0.105 |
Ca:HEMA | 8.9795 | 17.48 | 17.97 | 5.1542 | 2.6933 | 1.132 | 0 | 1.0295 | 22.5367 | 0 | 0.932 | 0 | 21.8928 | 0.2 |
Ca:HAp | 9.097 | 18.915 | 10.685 | 6.93 | 0.522 | 1.645 | 0 | 10.55 | 0.552 | 38.697 | 1.75 | 0 | 0.552 | 0.105 |
Ca:Pept. | 17.575 | 16.975 | 11.148 | 0.668 | 1.6767 | 19.9197 | 0 | 5.6533 | 0.298 | 0 | 22.258 | 0 | 0.298 | 3.52 |
Ca:SiO2 | 9.097 | 18.915 | 10.685 | 6.93 | 0.522 | 1.645 | 0 | 10.55 | 0.552 | 0 | 1.75 | 38.697 | 0.552 | 0.105 |
FLs:F | 0.35 | 1.9 | 2.25 | 3.46 | 3.5825 | 0.4725 | 45.2192 | 36.48 | 2.1 | 0 | 1.2792 | 0 | 2.1 | 0.8067 |
FLs:HEMA | 0.145 | 0.7175 | 0.8625 | 1.305 | 1.355 | 0.195 | 41.1858 | 12.2333 | 26.43 | 0 | 0.5 | 0 | 14.7558 | 0.305 |
FLs:HAp | 0 | 0 | 0 | 0 | 0 | 0 | 50 | 0 | 0 | 50 | 0 | 0 | 0 | 0 |
FLs:Pept. | 1.1862 | 0.9675 | 0.2187 | 7.92 | 1.91 | 11.0162 | 41.6228 | 4.1287 | 0.2067 | 0 | 28.4 | 0 | 0.2067 | 2.2067 |
FLs:SiO2 | 0 | 0 | 0 | 0 | 0 | 0 | 50 | 0 | 0 | 0 | 0 | 50 | 0 | 0 |
F:HAp | 0.35 | 1.9 | 2.25 | 3.46 | 3.5825 | 0.4725 | 0 | 36.48 | 2.1 | 45.2192 | 1.2792 | 0 | 2.1 | 0.8067 |
F:SiO2 | 0.35 | 1.9 | 2.25 | 3.46 | 3.5825 | 0.4725 | 0 | 36.48 | 2.1 | 0 | 1.2792 | 45.2192 | 2.1 | 0.8067 |
HEMA:HAp | 0.145 | 0.7175 | 0.8625 | 1.305 | 1.355 | 0.195 | 0 | 12.2333 | 26.43 | 41.1858 | 0.5 | 0 | 14.7558 | 0.305 |
HEMA:Pept. | 1.4625 | 0.2 | 1.2625 | 4.635 | 4.37 | 10.4675 | 0 | 5.7817 | 25.81 | 0 | 26.757 | 0 | 15.3342 | 3.92 |
HEMA:SiO2 | 0.145 | 0.7175 | 0.8625 | 1.305 | 1.355 | 0.195 | 0 | 12.2333 | 26.43 | 0 | 0.5 | 41.1858 | 14.7558 | 0.305 |
HAp:Pept. | 1.1862 | 0.9675 | 0.2187 | 7.92 | 1.91 | 11.0162 | 0 | 4.1287 | 0.2067 | 41.623 | 28.4 | 0 | 0.2067 | 2.2067 |
HAp:SiO2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 50 | 0 | 50 | 0 | 0 |
Pept.:SiO2 | 1.1862 | 0.9675 | 0.2187 | 7.92 | 1.91 | 11.0162 | 0 | 4.1287 | 0.2067 | 0 | 28.4 | 41.6228 | 0.2067 | 2.2067 |
Appendix A.5. Confidence Rating Output of CINeMA Software
Comparison | Number of Studies | Within-Study Bias | Reporting Bias | Indirectness | Imprecision | Heterogeneity | Incoherence | Confidence Rating |
---|---|---|---|---|---|---|---|---|
Mixed estimates | ||||||||
CaP:CTRL | 1 | Some concerns | Low risk | No concerns | Major concerns | No concerns | No concerns | Low |
CaP:F | 1 | Some concerns | Low risk | No concerns | Major concerns | No concerns | No concerns | Low |
CaP:Pept. | 1 | Some concerns | Low risk | No concerns | Major concerns | No concerns | No concerns | Low |
Ca:CaP | 7 | Some concerns | Low risk | No concerns | No concerns | Major concerns | No concerns | Low |
Ca:CTRL | 3 | Some concerns | Low risk | No concerns | No concerns | Major concerns | Major concerns | Very low |
Ca:F | 4 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | No concerns | Moderate |
CTRL:F | 8 | Some concerns | Low risk | No concerns | No concerns | Major concerns | Major concerns | Very low |
CTRL:HAp | 3 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Major concerns | Low |
CTRL:Pept. | 4 | Some concerns | Low risk | No concerns | Some concerns | No concerns | No concerns | Moderate |
F:Pept. | 2 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | No concerns | Moderate |
Indirect estimates | ||||||||
CaP:HAp | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Major concerns | Low |
Ca:HAp | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Major concerns | Low |
Ca:Pept. | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Major concerns | Low |
F:HAp | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Major concerns | Low |
HAp:Pept. | 0 | Some concerns | Low risk | No concerns | Major concerns | No concerns | Major concerns | Very low |
ER with Biological | ||||||||
---|---|---|---|---|---|---|---|---|
Comparison | Number of Studies | Within-Study Bias | Reporting Bias | Indirectness | Imprecision | Heterogeneity | Incoherence | Confidence Rating |
Mixed estimates | ||||||||
CaP:CTRL | 2 | Some concerns | Low risk | No concerns | No concerns | No concerns | No concerns | Moderate |
CaP:F | 2 | Some concerns | Some concerns | No concerns | No concerns | No concerns | No concerns | Moderate |
CaP:Pept. | 2 | Some concerns | Low risk | No concerns | Some concerns | No concerns | No concerns | Moderate |
CTRL:FLs | 1 | Some concerns | Some concerns | No concerns | No concerns | Some concerns | No concerns | Moderate |
CTRL:F | 4 | Some concerns | Low risk | No concerns | No concerns | Some concerns | No concerns | Moderate |
CTRL:Pept. | 3 | Some concerns | Low risk | No concerns | No concerns | No concerns | No concerns | Moderate |
F:Pept. | 2 | Some concerns | Some concerns | No concerns | No concerns | No concerns | No concerns | Moderate |
Indirect estimates | ||||||||
CaP:FLs | 0 | Some concerns | Low risk | No concerns | No concerns | No concerns | No concerns | Moderate |
FLs:F | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | No concerns | Moderate |
FLs:Pept. | 0 | Some concerns | Low risk | No concerns | No concerns | Some concerns | No concerns | Moderate |
SE with Chemical | ||||||||
---|---|---|---|---|---|---|---|---|
Comparison | Number of Studies | Within-Study Bias | Reporting Bias | Indirectness | Imprecision | Heterogeneity | Incoherence | Confidence rating |
Mixed estimates | ||||||||
CaP:CTRL | 1 | Some concerns | Low risk | No concerns | Some concerns | No concerns | No concerns | Moderate |
CaP:F | 1 | Some concerns | Low risk | No concerns | No concerns | Some concerns | No concerns | Moderate |
CaP:Pept. | 1 | Some concerns | Low risk | No concerns | No concerns | Major concerns | No concerns | Low |
Ca:CaP | 4 | Some concerns | Low risk | No concerns | No concerns | Some concerns | Some concerns | Moderate |
Ca:CTRL | 2 | Some concerns | Low risk | No concerns | No concerns | Some concerns | No concerns | Moderate |
Ca:F | 3 | Some concerns | Low risk | No concerns | No concerns | Major concerns | No concerns | Low |
CTRL:FLs | 1 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
CTRL:F | 8 | Some concerns | Low risk | No concerns | No concerns | Some concerns | No concerns | Moderate |
CTRL:HEMA | 1 | Major concerns | Low risk | No concerns | Some concerns | No concerns | No concerns | Low |
CTRL:HAp | 5 | Some concerns | Low risk | No concerns | No concerns | Some concerns | Some concerns | Moderate |
CTRL:Pept. | 3 | Some concerns | Low risk | No concerns | No concerns | Some concerns | Some concerns | Moderate |
CTRL:SiO2 | 1 | Some concerns | Low risk | No concerns | No concerns | Major concerns | Some concerns | Low |
F:HEMA | 1 | Major concerns | Low risk | No concerns | Some concerns | No concerns | No concerns | Low |
F:Pept. | 1 | Some concerns | Low risk | No concerns | No concerns | Some concerns | Major concerns | Low |
Indirect estimates | ||||||||
CaP:FLs | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
CaP:HEMA | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
CaP:HAp | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
CaP:SiO2 | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
Ca:FLs | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
Ca:HEMA | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
Ca:HAp | 0 | Some concerns | Low risk | No concerns | No concerns | Major concerns | Some concerns | Low |
Ca:Pept. | 0 | Some concerns | Low risk | No concerns | No concerns | Some concerns | Some concerns | Moderate |
Ca:SiO2 | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
FLs:F | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
FLs:HEMA | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
FLs:HAp | 0 | Some concerns | Low risk | No concerns | No concerns | Some concerns | Some concerns | Moderate |
FLs:Pept. | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
FLs:SiO2 | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
F:HAp | 0 | Some concerns | Low risk | No concerns | No concerns | Some concerns | Some concerns | Moderate |
F:SiO2 | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
HEMA:HAp | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
HEMA:Pept. | 0 | Some concerns | Low risk | No concerns | No concerns | Major concerns | Some concerns | Low |
HEMA:SiO2 | 0 | Some concerns | Low risk | No concerns | Some concerns | Some concerns | Some concerns | Moderate |
HAp:Pept. | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
HAp:SiO2 | 0 | Some concerns | Low risk | No concerns | Some concerns | No concerns | Some concerns | Moderate |
Appendix A.6. Sensitivity Analyses
Random | Calcium | |||||
1.106 (−7.711, 9.922) | CaP | |||||
−0.123 (−8.738, 8.491) | −1.229 (−5.371, 2.913) | Control | ||||
−1.291 (−10.094, 7.512) | −2.397 (−7.595, 2.802) | −1.168 (−5.227, 2.892) | Fluorine | |||
5.813 (−4.953, 16.580) | 4.707 (−2.965, 12.380) | 5.937 (−0.522, 12.395) | 7.104 (−0.524, 14.733) | HAp | ||
5.028 (−4.929, 14.984) | 3.922 (−1.860, 9.704) | 5.151 (−0.520, 10.822) | 6.319 (−0.223, 12.860) | −0.786 (−9.381, 7.809) | Peptide | |
Without SB | Calcium | |||||
1.849 (−10.377, 14.074) | CaP | |||||
−1.065 (−12.941, 10.810) | −2.914 (−9.377, 3.549) | Control | ||||
−1.323 (−13.357, 10.710) | −3.172 (−10.460, 4.116) | −0.258 (−5.532, 5.016) | Fluorine | |||
3.777 (−10.759, 18.313) | 1.928 (−8.656, 12.513) | 4.842 (−3.540, 13.225) | 5.100 (−4.804, 15.004) | HAp | ||
5.947 (−8.203, 20.096) | 4.098 (−4.949, 13.145) | 7.012 (−1.747, 15.771) | 7.270 (−2.143, 16.683) | 2.170 (−9.954, 14.293) | Peptide |
Random | Calcium phosphate | ||||
−21.320 (−26.341, −16.299) | Control | ||||
−11.160 (−20.061, −2.258) | 10.160 (2.810, 17.510) | Flavonoids | |||
−17.063 (−22.451, −11.675) | 4.257 (0.806, 7.708) | −5.903 (−14.023, 2.217) | Fluorine | ||
−2.924 (−8.500, 2.652) | 18.396 (14.256, 22.535) | 8.236 (−0.200, 16.672) | 14.139 (9.408, 18.870) | Peptide |
Random | Calcium | ||||||||||||||
1.938 (−2.927, 6.803) | CaP | ||||||||||||||
1.437 (−3.182, 6.057) | −0.500 (−3.617, 2.616) | Control | |||||||||||||
10.407 (1.928, 18.887) | 8.470 (0.706, 16.233) | 8.970 (1.859, 16.081) | FLs | ||||||||||||
0.937 (−3.774, 5.649) | −1.000 (−4.507, 2.507) | −0.500 (−2.804, 1.804) | −9.470 (−16.945, −1.995) | Fluorine | |||||||||||
0.768 (−5.753, 7.290) | −1.169 (−6.806, 4.467) | −0.669 (−5.510, 4.172) | −9.639 (−18.241, −1.036) | −0.169 (−5.004, 4.667) | HEMA | ||||||||||
−3.124 (−8.605, 2.357) | −5.061 (−9.352, −0.771) | −4.561 (−7.511, −1.611) | −13.531 (−21.230, −5.832) | −4.061 (−7.804, −0.318) | −3.892 (−9.561, 1.776) | HAp | |||||||||
4.256 (−1.421, 9.932) | 2.318 (−1.565, 6.201) | 2.818 (−0.994, 6.632) | −6.152 (−14.220, 1.917) | 3.318 (−0.931, 7.568) | 3.487 (−2.601, 9.576) | 7.380 (2.559, 12.200) | Peptide | ||||||||
2.277 (−5.235, 9.789) | 0.340 (−6.354, 7.033) | 0.840 (−5.084, 6.764) | −8.130 (−17.385, 1.125) | 1.340 (−5.016, 7.696) | 0.509 (−6.141, 9.159) | 5.401 (−1.217, 12.019) | −1.978 (−9.024, 5.066) | Silica | |||||||
Without SB | Calcium | ||||||||||||||
3.937 (−3.398, 11.273) | CaP | ||||||||||||||
0.117 (−6.760, 6.994) | −3.820 (−9.111, 1.471) | Control | |||||||||||||
4.721 (−6.357, 15.800) | 0.784 (−9.386, 10.954) | 4.604 (−4.082, 13.290) | FLs | ||||||||||||
0.254 (−6.695, 7.203) | −3.684 (−9.251, 1.884) | 0.137 (−3.243, 3.516) | −4.467 (−13.787, 4.853) | Fluorine | |||||||||||
−2.875 (−10.771, 5.021) | −6.812 (−13.373, −0.252) | −2.992 (−6.871, 0.887) | −7.596 (−17.108, 1.916) | −3.129 (−8.273, 2.016) | HAp | ||||||||||
−2.811 (−11.987, 6.365) | −6.748 (−13.994, 0.498) | −2.928 (−9.722, 3.866) | −7.532 (−18.559, 3.495) | −3.065 (−10.240, 4.111) | 0.064 (−7.759, 7.888) | Peptide |
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Plot of the NMA ER + Chemical ACAD | Plot of the NMA ER + Biological ACAD | Plot of the NMA SE + Chemical ACAD |
NMA | NMA Results | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ER + chemical | Calcium | |||||||||||||||
0.596 (−7.289, 8.482) | Calcium Phosphate | |||||||||||||||
−0.508 (−8.207, 7.191) | −1.105 (−4.828, 2.619) | Control | ||||||||||||||
−0.628 (−8.504, 7.248) | −1.224 (−5.931, 3.482) | −0.120 (−3.783, 3.544) | Fluorine | |||||||||||||
4.333 (−5.240,13.906) | 3.736 (−3.063, 0.536) | 4.841 (−0.848,10.530) | 4.960 (−1.806,11.727) | HAp | ||||||||||||
4.044 (−4.923, 3.011) | 3.448 (−1.833, 8.729) | 4.553 (−0.635, 9.740) | 4.672 (−1.320,10.665) | −0.288 (−7.988, 7.411) | Peptide | |||||||||||
ER + biological | Calcium Phosphate | |||||||||||||||
−21.209 (−25.954, −16.463) | Control | |||||||||||||||
−12.771 (−20.538, −5.003) | 8.438 (2.289, 14.587) | Flavonoids | ||||||||||||||
−17.012 (−22.103, −11.920) | 4.197 (1.080, 7.314) | −4.241 (−11.135, 2.652) | Fluorine | |||||||||||||
−2.914 (−8.210, 2.382) | 18.295 (14.418, 22.172) | 9.857 (2.588, 17.126) | 14.098 (9.684, 18.512) | Peptide | ||||||||||||
SE + chemical | Calcium | |||||||||||||||
2.663 (−2.395, 7.722) | Calcium Phosphate | |||||||||||||||
1.124 (−3.670, 5.917) | −1.539 (−4.817, 1.738) | Control | ||||||||||||||
5.728 (−2.442,13.897) | 3.065 (−4.318, 10.447) | 4.604 (−2.011, 11.219) | Flavonoids | |||||||||||||
0.523 (−4.358, 5.404) | −2.140 (−5.787, 1.506) | −0.601 (−2.932, 1.730) | −5.205 (−12.219, 1.809) | Fluorine | ||||||||||||
3.023 (−3.815, 9.861) | 0.360 (−5.589, 6.309) | 1.899 (−3.210, 7.009) | −2.705 (−11.063, 5.654) | 2.500 (−2.603, 7.603) | HEMA | |||||||||||
−1.792 (−7.415, 3.831) | −4.455 (−8.857, −0.053) | −2.916 (−5.854, 0.023) | −7.520 (−14.758, −0.281) | −2.315 (−6.066, 1.436) | −4.815 (−10.709, 1.079) | HAp | ||||||||||
2.654 (−3.216, 8.524) | −0.009 (−4.076, 4.058) | 1.530 (−2.373, 5.434) | −3.074 (−10.755, 4.607) | 2.131 (−2.213, 6.475) | −0.369 (−6.728, 5.990) | 4.446 (−0.440, 9.332) | Peptide | |||||||||
1.964 (−5.802, 9.730) | −0.699 (−7.633, 6.234) | 0.840 (−5.270, 6.950) | −3.764 (−12.769, 5.241) | 1.441 (−5.099, 7.980) | −1.059 (−9.024, 6.906) | 3.756 (−3.024, 10.536) | −0.690 (−7.941, 6.560) | Silica |
NMA | Ranks and Probability of Ranking Best | ||||
---|---|---|---|---|---|
ER + chemical | Rank | ||||
Mean | Median | CrI95% | Probability of ranking best (%) | ||
Control | 4.66 | 5 | (3.6) | 0.05−4 | |
Fluorine | 4.66 | 5 | (2.6) | 0.64 | |
CaP | 3.75 | 4 | (2.6) | 1.75 | |
Peptide | 1.92 | 2 | (1.5) | 41.55 | |
Calcium | 4.06 | 4 | (1.6) | 9.91 | |
HAp | 1.97 | 2 | (1.5) | 46.10 | |
ER + biological | Rank | ||||
Mean | Median | CrI95% | Probability of ranking best (%) | ||
Control | 4.98 | 5 | (5.5) | 0.00 | |
Fluorine | 3.89 | 4 | (4.5) | 0.00 | |
CaP | 1.15 | 1 | (1.2) | 85.24 | |
Peptide | 1.86 | 2 | (1.2) | 14.56 | |
FLs | 3.12 | 3 | (3.4) | 0.20 | |
SE + chemical | Rank | ||||
Mean | Median | CrI95% | Probability of ranking best (%) | ||
Control | 5.49 | 6 | (3.6) | 0.11 | |
Fluorine | 5.96 | 6 | (3.9) | 0.32 | |
CaP | 3.28 | 3 | (1.7) | 12.41 | |
Peptide | 4.77 | 4 | (1.9) | 5.01 | |
Calcium | 6.00 | 7 | (1.9) | 4.15 | |
HAp | 7.89 | 8 | (4.9) | 0.09 | |
FLs | 2.75 | 2 | (1.9) | 46.36 | |
HEMA | 4.03 | 3 | (1.9) | 17.49 | |
Silica | 4.85 | 5 | (1.9) | 14.05 |
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Costa, R.; Reis-Pardal, J.; Arantes-Oliveira, S.; Ferreira, J.C.; Azevedo, L.F.; Melo, P. Biomimetic Remineralization Strategies for Dentin Bond Stability—Systematic Review and Network Meta-Analysis. Int. J. Mol. Sci. 2025, 26, 3488. https://doi.org/10.3390/ijms26083488
Costa R, Reis-Pardal J, Arantes-Oliveira S, Ferreira JC, Azevedo LF, Melo P. Biomimetic Remineralization Strategies for Dentin Bond Stability—Systematic Review and Network Meta-Analysis. International Journal of Molecular Sciences. 2025; 26(8):3488. https://doi.org/10.3390/ijms26083488
Chicago/Turabian StyleCosta, Rosário, Joana Reis-Pardal, Sofia Arantes-Oliveira, João Cardoso Ferreira, Luis Filipe Azevedo, and Paulo Melo. 2025. "Biomimetic Remineralization Strategies for Dentin Bond Stability—Systematic Review and Network Meta-Analysis" International Journal of Molecular Sciences 26, no. 8: 3488. https://doi.org/10.3390/ijms26083488
APA StyleCosta, R., Reis-Pardal, J., Arantes-Oliveira, S., Ferreira, J. C., Azevedo, L. F., & Melo, P. (2025). Biomimetic Remineralization Strategies for Dentin Bond Stability—Systematic Review and Network Meta-Analysis. International Journal of Molecular Sciences, 26(8), 3488. https://doi.org/10.3390/ijms26083488