Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis

Krisha Doshi; M. S. Nivedhitha; Pradeep Solete; Delphine Pricilla Antony S; Arthi Balasubramaniam; Benoy Jacob; Riluwan Siddique

doi:10.1038/s41405-022-00124-6

Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis

Doshi, Krisha; Nivedhitha, M. S.; Solete, Pradeep; S, Delphine Pricilla Antony; Balasubramaniam, Arthi; Jacob, Benoy; Siddique, Riluwan 2023-02-13 00:00:00 www.nature.com/bdjopen ARTICLE OPEN Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis 1 1 1 1 2 1 Krisha Doshi , M. S. Nivedhitha , Pradeep Solete , Delphine Pricilla Antony S , Arthi Balasubramaniam , Benoy Jacob and 1✉ Riluwan Siddique © The Author(s) 2023 OBJECTIVE: To determine the effect of adhesive strategy (total etch or self-etch) of universal adhesives in non-carious cervical lesions. DATA SOURCE: A search was made in PubMed, Scopus, Cochrane, Web Of Science, Open Gray, Clinical Registries. DATA SELECTION: Randomized Controlled Clinical Trials, studies on non-carious cervical lesions restored using Universal Adhesives, and studies in which universal adhesives have been used in total etch and self -etch strategies were included in this systematic review. DATA EXTRACTION: A total of 17 articles were included in the systematic review and 13 in the meta-analysis. Meta-analysis was conducted to assess the clinical performance of NCCLs in terms of retention, marginal adaptation, marginal discoloration, secondary caries and post-operative sensitivity at 18, 24, 36 month follow-up using USPHS as well as FDI criteria, separately. DATA SYNTHESIS: Overall there was no signiﬁcant difference between total etch and self etch adhesive strategies for any of the ﬁve outcome measures using either the FDI or the USPHS criteria. p > 0.05, 95% CI, I value of 0%. A strongly suspected publication bias in the retention domain was seen at 18 month follow up under FDI criteria. CONCLUSION: Most universal adhesives show acceptable clinical performance. There is no signiﬁcant effect of the adhesive strategy of universal adhesives on their clinical performance according to the results of our meta-analysis. BDJ Open (2023) 9:6 ; https://doi.org/10.1038/s41405-022-00124-6 INTRODUCTION dentin, as a result there is a decrease in bond strength [10–12]. In The advent of adhesive dentistry has revolutionized the ﬁeld of self-etch adhesive systems, the demineralization of the dental restorative dentistry. Scientiﬁc evidence shows that bonded substrates is produced by non-rinsing acidic primers mixed with restorations demonstrate an array of advantages including hydrophilic monomers such as HEMA. These primers dissolve the minimal invasion, better aesthetics, stronger bond strength, mineral component of the smear layer and alter the underlying reduced microleakage, better distribution of functional stresses superﬁcial dentin to receive the adhesive into the smear plugs and more favourable failures [1, 2]. [13]. The low bond strength and the inferior marginal adaptation Kramer and McLean in 1952 [3], were among the ﬁrst to use to the enamel are the drawbacks of self-etch adhesives when glycerophosphoric acid dimethacrylate (GPDM) to bond to dentin. compared to total-etch systems [14, 15]. They demonstrated certain alterations in the staining of dentin More recently, the introduction of Universal adhesives, also during histologic examination, that is presently known as the called multimode adhesives can be used with or without acid hybrid layer [4]. This pioneering work followed by Buonocore’s etching in both enamel and dentin [16–19]. Different researchers discovery of the acid-etch technique has led to major changes in have shown that universal adhesives have high bond strength bonding to tooth structure [5]. Over the years, dental adhesives values, and this is due to the acidic monomers that promote have progressed from three-step systems, to two-step systems chemical bonding to the tooth [18, 20]. and ﬁnally to single step systems [6]. The technique or adhesive Non-carious cervical lesions (NCCLs) are hard tissue defects in strategy has also developed from a more time-consuming and the cervical region of the teeth that are not caused by a bacterial technique sensitive total etch system to a simpler self-etch system. agent [21]. Restorations of NCCLs are common in the clinical The consensus of total-etch versus self-etch strategy for bonding setting, and represent one of the least durable restorations, with a has been widely debated over the past two decades [7–9]. high rate of retention loss, marginal discoloration and lack of The major disadvantage of the total etch system is that there is marginal adaptation. The major challenges in restoring NCCLs a risk of collagen ﬁbril collapse during drying of the demineralized include the difﬁculty in controlling moisture and obtaining access Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical And Technical Sciences (SIMATS), Chennai, Tamil Nadu, India. Department of Public Health Dentistry, Saveetha Dental College, Saveetha University, Chennai, India. email: riluwanas@gmail.com Received: 28 March 2022 Revised: 21 September 2022 Accepted: 23 September 2022 1234567890();,: K. Doshi et al. to the subgingival margins, as well as selecting the best adhesive makes the hybrid layer formation more difﬁcult on this surface strategy [22]. [23, 24]. Phosphoric acid conditioning before self-etch primers has The lack of enamel or macro-mechanical undercuts, high been suggested to improve the retention of these restorations degree of sclerosis and substantial differences in bonding surface [24]. Since, this effect has not been assessed sufﬁciently with Table 1. Search strategy. Search Engine Search strategy PubMed (((((((((((non carious cervical lesions) OR (non-carious cervical lesions)) OR (cervical abrasion)) OR (tooth abrasion)) OR (tooth erosion)) OR (cervical (27 results) lesions)) OR (NCCL)) OR (NCCLs)) OR (Class V)) OR (Class 5)) AND (((((((((((Dentin Bonding Agent) OR (Dental adhesives) OR (Universal adhesive) OR (Universal bonding agent)) OR (Multimode adhesives)) OR (Multi mode adhesives)) OR (eighth generation bonding agent)) OR (8th generation bonding agent)) OR (8th-generation bonding agent)) OR (eighth-generation bonding agent)) OR (eighth generation adhesive)) OR (8th generation adhesive))))) AND ((((((((((((Self etch) OR (self-etch)) OR (One step self etch)) OR (One-step self etch)) OR (one-step self-etch))OR (1 step self-etch)) OR (1-step self-etch)) OR (1-step self etch)) OR (self-etch technique)) OR (self-etch strategy)) OR (self-etching)) OR (self etching))) AND (((((((((total etch) OR (acid etching) OR (total-etch)) OR (etch and rinse)) OR (etch & rinse)) OR (etch-and-rinse)) OR (etch-&-rinse)) OR (total etch technique)) OR (total-etch technique)) OR (total-etching) AND ((((((((((post operative sensitivity) OR (post-operative sensitivity)) OR (postoperative sensitivity)) OR (retention)) OR (marginal adaptation)) OR (marginal discolouration)) OR (marginal staining)) OR (United States Public Health Service)) OR (FDI criteria)) OR (secondary caries)) Cochrane #1 (non-carious cervical lesions) OR (cervical abrasion) OR (cervical lesion) OR (NCCL) OR (Class V) (Word variations have been searched) (48 results) #2 MeSH descriptor: [Tooth Abrasion] this term only #3 MeSH descriptor: [Tooth Erosion] this term only #4 (Universal Adhesives) OR (Universal bonding agents) OR (Multimode adhesives) OR (Eighth generation bonding agents) OR (8th generation adhesives) (Word variations have been searched) #5 MeSH descriptor: [Dentin-Bonding Agents] this term only #6 (self etch) OR (one-step self etch) OR (Self-etching) OR (1 step self-etch) (Word variations have been searched) #7 (total etch) OR (etch and rinse) OR (etch & rinse) OR (acid etch) OR (acid etching) (Word variations have been searched) #8 MeSH descriptor: [Acid Etching, Dental] this term only #9 (FDI criteria) OR (marginal adaptation) OR (marginal discolouration) OR (“United States Public Health Service”) OR (marginal staining) (Word variations have been searched) #10 MeSH descriptor: [United States Public Health Service] this term only #11 (secondary caries) OR (retention) OR (postoperative sensitivity) OR (post-operative sensitivity) OR (post operative sensitivity) (Word variations have been searched) #12 #1 OR #2 OR #3 #13 #4 OR #5 #14 #7 OR #8 #15 #9 OR #10 OR #11 #16 #12 AND #13 AND #6 AND #14 AND #15 Scopus (TITLE-ABS-KEY (“Non-carious cervical lesion” OR “non carious cervical lesion” OR “cervical abrasion” OR “tooth abrasion” OR “tooth erosion” OR (43 results) nccl OR nccls)) AND (TITLE-ABS-KEY (“Dentin bonding agent” OR “Dental adhesive” OR “Universal Adhesive” OR “Universal bonding agent” OR “Multimode adhesive” OR “Multi mode adhesive” OR “Eighth generation adhesive” OR “8th generation adhesive” OR “Eighth generation bonding agent” OR “8th generation bonding agent”)) AND (TITLE-ABS-KEY (“self etch” OR {self-etch} OR “self etching” OR {self-etching})) AND (TITLE-ABS- KEY (“total etch” OR {total-etc} OR “total etching” OR {total-etching} OR “acid etch” OR “acid etching” OR “etch and rinse” OR {etch-and-rinse} OR “etching and rinsing” OR {etch-n-rinse})) AND (TITLE-ABS-KEY (“postoperative sensitivity” OR “post operative sensitivity” OR {post-operative sensitivity} OR retention OR “marginal adaptation” OR “marginal discolouration” OR “marginal staining” OR “secondary caries” OR “United States Public Health Service criteria” OR {USPHS criteria} OR {FDI criteria} OR “clinical evaluation” OR “clinical performance”)) Web of Science #6 (25 results) #5 AND #4 AND #3 AND #2 AND #1 Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #5 (ALL = (postoperative sensitivity OR post-operative sensitivity OR post operative sensitivity OR Retention OR secondary caries OR marginal discolouration OR marginal staining OR marginal adaptation OR United States Public Health Service OR FDI OR clinical evaluation OR clinical performance)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #4 (ALL = (self etch OR Self-etch OR self etching)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #3 (ALL = (Total etch OR total-etch OR etch and rinse OR acid etching OR total etching OR etching and rinsing)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #2 (ALL = (Universal adhesive OR universal bonding agent OR Multimode adhesive OR Multi-mode adhesive OR Eighth generation bonding agent OR 8th generation bonding agent)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #1 (All = (Non carious cervical lesion OR Cervical abrasion OR NCCL OR tooth abrasion OR tooth erosion)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years Open Grey Universal Adhesives AND Non-Carious Cervical Lesions (0 results) BDJ Open (2023) 9:6 K. Doshi et al. universal adhesives, the aim of this systematic review was to adaptation, Marginal discolouration, Retention, Secondary caries determine the effects of adhesive strategy (total etch or self-etch) and Post-operative sensitivity. of universal adhesives in non-carious cervical lesions. The Population (P) was patients requiring restoration of non-carious cervical lesions; Intervention (I) was the use of Universal adhesive MATERIALS AND METHODS This systematic review was performed following the Preferred Reporting in Self-etch adhesive strategy; Comparison (C) was the use of Items for Systematic Reviews (PRISMA 2020) guidelines (http:// Universal adhesive in total etch adhesive strategy and the www.prisma-statement.org) and the Cochrane Handbook of Systematic Outcome (O) was clinical evaluation in terms of Marginal Reviews of Interventions (Version 6.2.0) [25]. Identification of studies via databases and registers Protocol registration The protocol for this systematic review has been registered with the Records removed before PROSPERO International prospective register of systematic reviews, registry Records identified from*: screening: Pubmed (n =27) No. CRD42021250429. Duplicate records removed Scopus (n=43) (n=49) Cochrane (n=48) Records marked as ineligible Web of Science (n=25) by automation tools (n=0) Open Grey (n=0) Selection criteria Records removed for other Registers (n=0) reasons (n=0) Only Randomized Controlled Clinical Trials (RCTs) in which non-carious cervical lesions were restored using Universal adhesives in total etch or self etch strategy were included in the systematic review. In case of studies having publications with multiple follow ups, the publication with the longest Records screened Records excluded** (n=94) (n=73) follow up only was included. In-vitro studies, or studies on cavity designs other than NCCLs were excluded from this systematic review. Studies using adhesives other than universal adhesives, or those not assessing the clinical performance in terms of marginal adaptation, marginal discoloration, Studies sought for retrieval Studies not retrieved (n=21) (n=0) retention, secondary caries or post-operative sensitivity were also excluded. Search strategy Studies assessed for eligibility Studies excluded: A detailed search was done in the following databases: Medline (PubMed), (n=21) Multiple reports of same Cochrane, Scopus, Web of Science and OpenGrey and clinical trial registry study (n=4) for the identiﬁcation of relevant studies. The search queries in the database were formulated with the basis of PICO questions in combination with various Boolean operators such as AND, OR. MeSH terms used for the search included “Dentin bonding agent”, “Dental Adhesive”, “acid etching”, Studies excluded for meta- Studies included in Systematic analysis: “tooth abrasion”, ‘tooth erosion’, “United States Public Health Service”.No Review Studies with follow-up other language restriction was applied. Related articles and the reference lists of (n=17) than 18, 24 or 36 months (n=4) the articles that were retrieved by the search engines were manually checked for possible eligibility (Table 1). Studies included in Meta- Analysis Screening process (n=13) The search and screening process was carried out by two authors (Krisha Doshi, Pradeep Solete), independently. As a ﬁrst step, titles and abstracts Fig. 1 PRISMA Flowchart. Flowchart of Included Studies according were analyzed, followed by full text analysis. An in-depth analysis of the to PRISMA guidelines. Fig. 2 Risk of Bias Graph. Graph representing each risk of bias item presented as percentages across all included studies. BDJ Open (2023) 9:6 Screening Idenﬁcaon Included K. Doshi et al. Table 2. List of excluded studies with reasons. Author/Year Reason for exclusion Mena-serrano et al. (2012) (Mena-Serrano et al. 2013) Same study as Matos et al. 2020 with different follow up (Matos et al. 2020) Jorge Perdigao et al. (2014) (Perdigão et al. 2014) Same study as Matos et al. 2020 with different follow-up (Matos et al. 2020) Loguercio et al. (2015)(Loguercio et al. 2015) Same study as Matos et al. 2020 with different follow-up(Matos et al. 2020) Ruschel et al. (2018)(Ruschel et al. 2018) Same study as Ruschel et al. 2019 with different follow-up (Ruschel et al. 2019) Lopes et al. (2016)(Lopes et al. 2016) 6 month follow-up Haak et al. (2018)(Haak et al. 2018) 6 month follow-up Manarte-Monteiro et al. (2019)(Manarte-Monteiro et al. 2019) 12 month follow-up Cruz et al. 2020(Cruz et al. 2020) 6 month follow-up articles for inclusion or exclusion was performed by the two authors separately to include in the systematic review. Any disagreement in selecting the articles between the authors was resolved by discussion with the third author (Nivedhitha M. S.), who is a senior professor. Data extraction The studies that fulﬁlled the inclusion criteria were processed for the extraction of data. The data were recorded as follows: ﬁrst author and year of publication, type of study, sample size, mean age and gender of the participants, followup period, study groups, number of teeth per group, isolation method, criteria used for clinical evaluation and clinical evaluation scores per group. The information regarding assessment of the risk of bias was also collected. The extraction of the information was done by two independent authors (Krisha Doshi, Pradeep Solete) using a standard form. Incase of any disagreement between the reviewers it was resolved by the third author (Nivedhitha M. S.), who is a senior professor. Methodological quality assessment of included studies The evaluation of the methodological quality of the included studies was assessed using the bias risk assessment tool (RoB 2), described in the Cochrane Handbook of Systematic Reviews of Interventions (Version 6.2.0) [25]. Brieﬂy, ﬁve domains were evaluated: (a) bias arising from the randomization process; (b) bias due to deviations from intended interventions; (c) bias due to missing outcome data; (d) bias in measurement of the outcome; and (e) bias in selection of the reported result. Meta-analysis The studies that had 18, 24 or 36 month follow up were included in the meta analysis. Comparison was made separately for each time interval. Meta analyses for FDI and USPHS criteria were conducted separately. - - - Akarsu et al 2020 ? + + Events of retention, marginal adaptation, absence of marginal discolora- tion, absence of secondary caries and absence of post-operative sensitivity Atalay et al 2019 - ? - + + - were analysed as dichotomized values. Since both FDI and USPHS criteria Costa et al 2020 + ? + + + ? were assessed for the above mentioned ﬁve factors, a subgroup meta- Cruz et al 2020 ? + + + + ? analysis was conducted. Estimates of intervention effects were expressed as Risk Ratios (RR) with de Albuquerque et al 2020 + + + + + + 95% conﬁdence intervals. The Mantel-Haenszel method which estimates - - Haak et al 2018 ? + + + risk ratio after adjusting for confounders was used. Heterogeneity was Kemaloglu et al 2020 + ? + - + - assessed using I statistics. Values <25% were considered as low heterogeneity, between 25% and 70% were considered as moderate Lawson et al 2015 ? + + + + ? heterogeneity, >70% were considered as high heterogeneity. Fixed effect Loguercio et al 2017 + + + + + + model was used if the I value was <40% and a random effect model was Lopes et al 2016 + + + + + + used when the I value was >40%. The signiﬁcance level was set at Manarte-Monteiro et al 2019 + - - + + - p ≤ 0.05. Publication bias for the included studies was examined by constructing Matos et al 2019 + + + + + + a funnel plot. Asymmetry of the studies in the funnel plot may reﬂect Matos et al 2020 + + + + + + publication bias. Data from the included studies were analyzed using - - - OZ et al 2019 + + + RevMan Web (Cochrane’s online review writing platform, The Cochrane Collaboration, Copenhagen, Denmark). Perdiagao et al 2019 + + + + + + Ruschel et al 2019 ? - - - + - Certainty of evidence assessment Zanatta et al 2019 + ? + + + ? Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (GRADEpro GDT software https://gradepro.org) was Fig. 3 Risk of bias summary. Graph representing the percentage of used to assess certainty of evidence from the meta-analysis which graded bias under each category assessed using Cochrane’s risk of bias evidence into very low, low, moderate or high quality. assessment tool. BDJ Open (2023) 9:6 Bias arising from the randomization process Bias due to deviations from intended interventions: Self-etch vs Total-etch Bias due to missing outcome data: Self-etch vs Total-etch Bias in measurement of the outcome: Self-etch vs Total-etch Bias in selection of the reported result: Self-etch vs Total-etch Overall bias: Self-etch vs Total-etch K. Doshi et al. Bias arising from the randomization process Bias due to deviations from intended interventions: Self-etch vs Total-etch Bias due to missing outcome data: Self-etch vs Total-etch Bias in measurement of the outcome: Self-etch vs Total-etch Bias in selection of the reported result: Self-etch vs Total-etch Overall bias: Self-etch vs Total-etch 0% 25% 50% 75% 100% Low risk of bias Some concerns High risk of bias Fig. 4 General Characteristics of included studies. Distribution of gender, adhesive, evaluation criteria, Isolation method, follow-up and Sample size among various included studies. Self-etch Total-etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 1.1.1 Retention Loguercio et al 2017 45 45 46 46 5.5% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 44 53 51 52 0.6% 0.85 [0.75 , 0.96] + + + + + + Matosetal2020 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Costa et al 2020 34 35 35 35 1.6% 0.97 [0.90 , 1.05] + ? + + + ? Subtotal (95% CI) 221 224 14.2% 0.97 [0.92 , 1.03] Total events: 207 219 Heterogeneity: Tau² = 0.00; Chi² = 11.83, df = 4 (P = 0.02); I² = 66% Test for overall effect: Z = 0.92 (P = 0.36) 1.1.2 Absence of marginal discoloration Loguercio et al 2017 43 43 46 46 5.2% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Matosetal2020 49 49 49 49 6.4% 1.00 [0.96 , 1.04] + + + + + + Costa et al 2020 35 35 35 35 3.3% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 215 223 21.6% 1.00 [0.98 , 1.02] Total events: 211 219 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 4 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 1.1.3 Marginal adaptation Loguercio et al 2017 45 45 47 47 5.6% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 34 42 38 42 0.3% 0.89 [0.75 , 1.07] + + + + + + Matosetal2020 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + Costa et al 2020 35 35 35 35 3.3% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 214 224 21.3% 1.00 [0.98 , 1.02] Total events: 206 220 Heterogeneity: Tau² = 0.00; Chi² = 3.90, df = 4 (P = 0.42); I² = 0% Test for overall effect: Z = 0.15 (P = 0.88) 1.1.4 Absence of secondary caries Loguercio et al 2017 45 45 47 47 5.6% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + Matosetal2020 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Costa et al 2020 35 35 35 35 3.3% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 214 224 21.5% 1.00 [0.98 , 1.02] Total events: 210 220 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 4 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 1.1.5 Absence of post-operative sensitivity Loguercio et al 2017 45 45 46 46 5.5% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Matosetal2020 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + Costa et al 2020 35 35 3.3% 1.00 [0.95 , 1.06] 35 35 + ? + + + ? Subtotal (95% CI) 214 223 21.4% 1.00 [0.98 , 1.02] Total events: 210 219 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 4 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) Total (95% CI) 1078 1118 100.0% 1.00 [0.99 , 1.01] Total events: 1044 1097 Heterogeneity: Tau² = 0.00; Chi² = 12.47, df = 24 (P = 0.97); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.36 (P = 0.72) Self-etch Total etch Test for subgroup differences: Chi² = 0.81, df = 4 (P = 0.94), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (C) Bias due to missing outcome data: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (D) Bias in measurement of the outcome: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (E) Bias in selection of the reported result: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (F) Overall bias: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria Fig. 5 Forest plot representing the pooled events at 18months using FDI criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 1.2.1 Retention Loguercio et al 2017 45 48 46 46 1.2% 0.94 [0.86 , 1.02] + + + + + + Matos et al 2019 46 48 51 51 1.6% 0.96 [0.89 , 1.03] + + + + + + Perdiagao et al 2019 22 25 27 27 0.3% 0.88 [0.75 , 1.03] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - - - ? + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 12 20 16 20 0.0% 0.75 [0.49 , 1.14] - ? + - + - Subtotal (95% CI) 282 288 14.6% 0.97 [0.93 , 1.02] Total events: 262 280 Heterogeneity: Tau² = 0.00; Chi² = 13.21, df = 6 (P = 0.04); I² = 55% Test for overall effect: Z = 1.25 (P = 0.21) 1.2.2 Absence of marginal discoloration Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Perdiagao et al 2019 20 22 27 27 0.4% 0.91 [0.78 , 1.06] + + + + + + Matos et al 2019 46 46 51 51 5.1% 1.00 [0.96 , 1.04] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - ? - + + - Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Akarsu et al 2020 12 12 16 16 0.4% 1.00 [0.87 , 1.15] - ? + - + - Subtotal (95% CI) 266 284 21.9% 1.00 [0.98 , 1.02] Total events: 260 280 Heterogeneity: Tau² = 0.00; Chi² = 2.04, df = 6 (P = 0.92); I² = 0% Test for overall effect: Z = 0.16 (P = 0.87) 1.2.3 Marginal adaptation Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Matos et al 2019 46 46 58 0.8% 1.13 [1.02 , 1.25] 51 + + + + + + Perdiagao et al 2019 22 22 27 27 1.3% 1.00 [0.92 , 1.08] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - - - ? + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 12 12 16 16 0.4% 1.00 [0.87 , 1.15] - ? + - + - Subtotal (95% CI) 266 291 18.5% 1.01 [0.98 , 1.04] Total events: 262 280 Heterogeneity: Tau² = 0.00; Chi² = 8.09, df = 6 (P = 0.23); I² = 26% Test for overall effect: Z = 0.57 (P = 0.57) 1.2.4 Absence of secondary caries Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Matos et al 2019 46 46 51 51 5.1% 1.00 [0.96 , 1.04] + + + + + + Perdiagao et al 2019 22 22 27 27 1.3% 1.00 [0.92 , 1.08] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - ? - + + - de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 12 12 16 16 0.4% 1.00 [0.87 , 1.15] - ? + - + - Subtotal (95% CI) 266 284 22.8% 1.00 [0.98 , 1.02] Total events: 262 280 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 6 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 1.2.5 1.2.5 Absence of post-operative sensitivity Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Perdiagao et al 2019 22 22 27 1.3% 27 1.00 [0.92 , 1.08] + + + + + + Matos et al 2019 46 46 51 51 5.1% 1.00 [0.96 , 1.04] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - - - ? + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 46 46 4.6% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 10 12 13 16 0.1% 1.03 [0.73 , 1.45] - ? + - + - Subtotal (95% CI) 266 281 22.2% 1.00 [0.98 , 1.02] Total events: 260 274 Heterogeneity: Tau² = 0.00; Chi² = 0.03, df = 6 (P = 1.00); I² = 0% Test for overall effect: Z = 0.01 (P = 0.99) Total (95% CI) 1346 1428 100.0% 1.00 [0.99 , 1.01] Total events: 1306 1394 Heterogeneity: Tau² = 0.00; Chi² = 16.21, df = 34 (P = 1.00); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.29 (P = 0.77) Self-etch Total-etch Test for subgroup differences: Chi² = 1.89, df = 4 (P = 0.76), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (C) Bias due to missing outcome data: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (D) Bias in measurement of the outcome: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (E) Bias in selection of the reported result: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (F) Overall bias: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria Fig. 6 Forest plot representing the pooled events at 18 months using USPHS criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. RESULTS In these cases, the article with the richest information (longest Search and selection follow-up) was chosen and included in this review. Hence a total Study selection and exclusion is depicted in Fig. 1 and Table 2. of 17 articles were included in the qualitative analysis. 13 of the 17 Some studies reported multiple reports with different follow-ups. included articles had a follow up of either 18, 24 or 36 months and BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 2.2.1 Retention Zanatta et al (2019) 55 60 63 68 2.6% 0.99 [0.89 , 1.10] - - - + + + Costa et al (2020) 32 36 34 35 1.6% 0.92 [0.80 , 1.04] + ? + + + ? Subtotal (95% CI) 96 103 4.3% 0.96 [0.89 , 1.04] Total events: 87 97 Heterogeneity: Tau² = 0.00; Chi² = 0.88, df = 1 (P = 0.35); I² = 0% Test for overall effect: Z = 1.00 (P = 0.32) 2.2.2 Absence of marginal discoloration Zanatta et al (2019) 51 53 60 63 4.6% 1.01 [0.94 , 1.09] + - - + + - Costa et al (2020) 34 34 34 34 8.5% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 87 97 13.1% 1.00 [0.96 , 1.05] Total events: 85 94 Heterogeneity: Tau² = 0.00; Chi² = 0.06, df = 1 (P = 0.81); I² = 0% Test for overall effect: Z = 0.16 (P = 0.88) 2.2.3 Marginal adaptation Zanatta et al (2019) 55 55 63 63 24.9% 1.00 [0.97 , 1.03] + - - + + - Costa et al (2020) 32 34 34 34 2.7% 0.94 [0.85 , 1.04] + ? + + + ? Subtotal (95% CI) 89 97 27.6% 0.98 [0.91 , 1.06] Total events: 87 97 Heterogeneity: Tau² = 0.00; Chi² = 2.19, df = 1 (P = 0.14); I² = 54% Test for overall effect: Z = 0.51 (P = 0.61) 2.2.4 Absence of secondary caries Zanatta et al (2019) 55 55 63 63 24.9% 1.00 [0.97 , 1.03] - - - + + + Costa et al (2020) 34 34 34 34 8.5% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 89 97 33.4% 1.00 [0.97 , 1.03] Total events: 89 97 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 2.2.5 Absence of post-operative sensitivity Zanatta et al (2019) 54 54 62 63 13.0% 1.01 [0.97 , 1.06] + - - + + - Costa et al (2020) 34 34 34 34 8.5% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 88 97 21.6% 1.01 [0.97 , 1.05] Total events: 88 96 Heterogeneity: Tau² = 0.00; Chi² = 0.16, df = 1 (P = 0.69); I² = 0% Test for overall effect: Z = 0.49 (P = 0.63) Total (95% CI) 449 491 100.0% 1.00 [0.98 , 1.02] Total events: 436 481 Heterogeneity: Tau² = 0.00; Chi² = 4.59, df = 9 (P = 0.87); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.12 (P = 0.91) Self-etch Total etch Test for subgroup differences: Chi² = 1.52, df = 4 (P = 0.82), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 24th month under FDI criteria (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 24th month under FDI criteria (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 24th month under FDI criteria (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 24th month under FDI criteria (F) Overall bias: Comparison of self-etching and conventional at 24th month under FDI criteria Fig. 7 Forest plot representing the pooled events at 24 months using FDI criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. were included in the meta-analysis. Sub-group analysis was retraction cord as the choice of isolation method. The follow-up performed at each of the follow-up periods (18, 24 and 36 months), period ranged from 6 months to 5 years with maximum studies separately. lying in the range of 18–36 months. Most of the available literature did not purely compare the two Study characteristics adhesive strategies—self-etch and total-etch. They usually The study characteristics of the included studies are presented in included one or more interventions. Some of these interventions online Supplementary Table 1 and Fig. 2. A total of 2622 teeth included comparison between dry dentin and moist dentin [MD9] were evaluated from 596 patients. 687 restorations were within the total-etch group [26–28]; selective enamel etch evaluated in the self-etch group while 696 restorations were adhesive strategy [26, 27, 29–31]; effect of dentine roughness evaluated in the total-etch group. The age of the patients ranged [32]; use of optical coherence tomography for evaluation of from 20 to 60 years. 273 of the patients were males wile 256 were quality of restorations [33]; addition of copper into the adhesive females. Scotchbond Universal and Single Bond Universal were [34]; comparison with self-etch and total-etch adhesives the most commonly used adhesives. 17 studies used either USPHS [30, 31, 35]; effect of diode laser [36]; and catechin-based dentin or FDI or both criteria for evaluation of the restorations. An equal pretreatment [37]. Only relevant data pertaining to this review was number of studies used rubber dam and cotton rolls with gingival collected from these articles. BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 2.1.1 Retention Lawson et al 2015 36 36 38 38 5.5% 1.00 [0.95 , 1.05] ? + + + + ? OZ et al 2019 25 34 36 36 0.6% 0.74 [0.60 , 0.91] + - - + + - Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 173 177 21.1% 0.97 [0.90 , 1.05] Total events: 164 177 Heterogeneity: Tau² = 0.00; Chi² = 25.61, df = 3 (P < 0.0001); I² = 88% Test for overall effect: Z = 0.77 (P = 0.44) 2.1.2 Absence of marginal discoloration Lawson et al 2015 36 36 38 38 5.5% 1.00 [0.95 , 1.05] ? + + + + ? OZ et al 2019 25 25 36 36 4.2% 1.00 [0.94 , 1.07] + - - + + - Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 164 177 24.6% 1.00 [0.98 , 1.02] Total events: 164 177 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 3 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 2.1.3 Marginal adaptation Lawson et al 2015 36 36 38 38 5.5% 1.00 [0.95 , 1.05] ? + + + + ? Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - OZ et al 2019 25 34 36 36 0.6% 0.74 [0.60 , 0.91] + - - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 173 177 21.1% 0.97 [0.90 , 1.05] Total events: 164 177 Heterogeneity: Tau² = 0.00; Chi² = 25.61, df = 3 (P < 0.0001); I² = 88% Test for overall effect: Z = 0.77 (P = 0.44) 2.1.4 Absence of secondary caries Lawson et al 2015 34 36 37 38 2.4% 0.97 [0.88 , 1.07] ? + + + + ? Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - OZ et al 2019 25 25 36 36 4.2% 1.00 [0.94 , 1.07] + - - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 164 177 21.5% 1.00 [0.97 , 1.02] Total events: 162 176 Heterogeneity: Tau² = 0.00; Chi² = 0.51, df = 3 (P = 0.92); I² = 0% Test for overall effect: Z = 0.16 (P = 0.87) 2.1.5 Absence of post-operative sensitivity Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - - - ? + + OZ et al 2019 25 25 36 36 4.2% 1.00 [0.94 , 1.07] + - - + + - Subtotal (95% CI) 78 89 11.8% 1.00 [0.97 , 1.03] Total events: 78 89 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) Total (95% CI) 752 797 100.0% 1.00 [0.98 , 1.01] Total events: 732 796 Heterogeneity: Tau² = 0.00; Chi² = 34.63, df = 17 (P = 0.007); I² = 51% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.53 (P = 0.60) Self-etch Total-etch Test for subgroup differences: Chi² = 1.06, df = 4 (P = 0.90), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 24th month under USPHS criteria (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 24th month under USPHS criteria (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 24th month under USPHS criteria (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 24th month under USPHS criteria (F) Overall bias: Comparison of self-etching and conventional at 24th month under USPHS criteria Fig. 8 Forest plot representing the pooled events at 24 months using USPHS criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. Methodological quality assessment of included studies [29–31, 33, 36, 38, 39] out of 17 included articles had a high Theresult ofthe qualityassessment ofRCTsofthe systematic risk of bias, 4 [9, 35, 37, 40] studies showed some concerns and 6 review is presented as risk of bias summary and risk of bias [26–28, 32, 34, 41] studies had a low risk of bias. In speciﬁc, the graph (Figs. 3, 4). As evaluated by the RoB2 tool, 7 highest risk was seen in the bias due to deviation from the BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI A B C D E F 3.2.1 Retention Matos et al 2020 40 45 44 45 20.5% 0.91 [0.81 , 1.02] + + + + + + Subtotal (95% CI) 45 45 20.5% 0.91 [0.81 , 1.02] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 1.66 (P = 0.10) 3.2.2 Absence of marginal discoloration Matos et al 2020 40 40 44 44 19.8% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 40 44 19.8% 1.00 [0.96 , 1.05] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) 3.2.3 Marginal adaptation Matos et al 2020 40 40 44 44 19.8% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 40 44 19.8% 1.00 [0.96 , 1.05] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) 3.2.4 Absence of secondary caries Matos et al 2020 40 40 44 44 19.8% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 40 44 19.8% 1.00 [0.96 , 1.05] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) 3.2.5 Absence of post-operative sensitivity Matos et al 2020 42 42 44 44 20.2% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 42 44 20.2% 1.00 [0.96 , 1.05] Total events: 42 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) Total (95% CI) 207 221 100.0% 0.98 [0.95 , 1.01] Total events: 202 220 Heterogeneity: Chi² = 4.38, df = 4 (P = 0.36); I² = 9% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 1.28 (P = 0.20) Self-etch Total-etch Test for subgroup differences: Chi² = 2.66, df = 4 (P = 0.62), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 36th month under FDI (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 36th month under FDI (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 36th month under FDI (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 36th month under FDI (F) Overall bias: Comparison of self-etching and conventional at 36th month under FDI Fig. 9 Forest plot representing the pooled events at 36 months using FDI criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. intended interventions domain with 3 studies [30, 31, 39]athigh Subgroup analysis. The outcome of retention, although insignif- risk and 5 studies [29, 35–38] showing some concerns. In the icant, slightly favoured the self-etch strategy at each follow-up for randomization and allocation concealment domain, 2 studies both the FDI and the USPHS criteria. [29, 36] showed a high risk of bias while 4 studies [9, 33, 39, 40] The outcome of marginal discolouration showed no difference showed some concerns. 4 studies [29–31, 39] showed a high risk between the two adhesive strategies at any follow-up period for of bias due to missing data and measurement of outcome any criteria. assessment. All studies showed a low risk of bias in selection of The outcome of marginal adaptation, although insigniﬁcant, reported results. showed a slight favour towards the self-etch adhesive strategy at the 24 month follow-up for both the criteria. The 36 month follow- Meta-analyses up showed no difference between the two adhesive strategies. A total of thirteen studies which compared self-etch and the total The outcome of secondary caries showed no difference between etch adhesive strategy using FDI and USPHS criteria were included the two adhesive strategies at any follow-up period for any criteria. in the meta analysis. The forest plot was produced according to The outcome of post-operative sensitivity showed no difference the FDI and USPHS criteria for the ﬁve outcome measures. between the two adhesive strategies at any follow-up period for any criteria. Group analysis. Overall there was no signiﬁcant difference between total etch and self- etch adhesive strategies using either Sensitivity analysis. A sensitivity analysis was also done by the FDI or the USPHS criteria. (p > 0.05, 95% CI, I value of 0%) at eliminating the studies with a high risk of bias. No signiﬁcant 18, 24 or 36 months. (Figs. 5–10) difference was observed in the meta-analysis. BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total-etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 3.1.1 Retention Perdiagao et al 2019 19 25 27 27 0.3% 0.76 [0.61 , 0.96] + + + + + + Atalay et al 2019 53 53 53 53 10.0% 1.00 [0.96 , 1.04] - ? - + + - Ruschel et al 2019 36 36 39 39 5.0% 1.00 [0.95 , 1.05] ? - - - + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 154 163 21.5% 0.98 [0.92 , 1.05] Total events: 148 163 Heterogeneity: Tau² = 0.00; Chi² = 13.69, df = 3 (P = 0.003); I² = 78% Test for overall effect: Z = 0.53 (P = 0.60) 3.1.2 Absence of marginal discoloration Perdiagao et al 2019 19 19 26 27 1.0% 1.03 [0.92 , 1.15] + + + + + + Atalay et al 2019 53 53 53 53 10.0% 1.00 [0.96 , 1.04] - - - ? + + Ruschel et al 2019 35 36 39 39 2.4% 0.97 [0.90 , 1.05] ? - - - + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 148 163 19.6% 1.00 [0.97 , 1.02] Total events: 147 162 Heterogeneity: Tau² = 0.00; Chi² = 0.82, df = 3 (P = 0.84); I² = 0% Test for overall effect: Z = 0.14 (P = 0.89) 3.1.3 Marginal adaptation Perdiagao et al 2019 19 19 27 27 1.8% 1.00 [0.92 , 1.09] + + + + + + Atalay et al 2019 53 53 53 53 10.0% 1.00 [0.96 , 1.04] - ? - + + - Ruschel et al 2019 34 36 39 39 1.5% 0.94 [0.86 , 1.04] - - - - ? + Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 148 163 19.5% 1.00 [0.97 , 1.02] Total events: 146 163 Heterogeneity: Tau² = 0.00; Chi² = 1.81, df = 3 (P = 0.61); I² = 0% Test for overall effect: Z = 0.34 (P = 0.74) 3.1.4 Absence of secondary caries Perdiagao et al 2019 19 19 27 27 1.8% 1.00 [0.92 , 1.09] + + + + + + Atalay et al 2019 53 53 52 52 9.8% 1.00 [0.96 , 1.04] - - - ? + + Ruschel et al 2019 36 36 39 39 5.0% 1.00 [0.95 , 1.05] ? - - - + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 148 162 22.8% 1.00 [0.98 , 1.02] Total events: 148 162 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 3 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 3.1.5 Absence of post-operative sensitivity Perdiagao et al 2019 18 19 25 27 0.6% 1.02 [0.88 , 1.19] + + + + + + Atalay et al 2019 53 53 52 52 9.8% 1.00 [0.96 , 1.04] - ? - + + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 112 123 16.6% 1.00 [0.97 , 1.03] Total events: 111 121 Heterogeneity: Tau² = 0.00; Chi² = 0.14, df = 2 (P = 0.93); I² = 0% Test for overall effect: Z = 0.06 (P = 0.96) Total (95% CI) 710 774 100.0% 1.00 [0.99 , 1.01] Total events: 700 771 Heterogeneity: Tau² = 0.00; Chi² = 10.25, df = 18 (P = 0.92); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.31 (P = 0.76) Self-etch Total-etch Test for subgroup differences: Chi² = 0.31, df = 4 (P = 0.99), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 36th month under USPHS criteria (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 36th month under USPHS criteria (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 36th month under USPHS criteria (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 36th month under USPHS criteria (F) Overall bias: Comparison of self-etching and conventional at 36th month under USPHS criteria Fig. 10 Forest plot representing the pooled events at 36 months using USPHS criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. Publication bias publication bias in the retention domain (Fig. 11). The funnel plot for comparison of self-etch and total-etch at However, the other domains showed no publication bias 18 month under FDI criteria revealed strongly suspected (Figs. 12–16). BDJ Open (2023) 9:6 K. Doshi et al. 0 SE(log[RR]) 0 SE(log[RR]) 0.02 0.05 0.04 0.1 0.06 0.15 0.08 RR RR 0.1 0.2 0.85 0.9 1 1.1 1.2 0.85 0.9 1 1.1 1.2 Subgroups Subgroups Retention Absence of secondary caries Retention Absence of secondary caries Absence of marginal discoloration Absence of post-operative sensitivity Absence of marginal discoloration Absence of post-operative sensitivity Marginal adaptation Marginal adaptation Fig. 11 Funnel plot representing asymmetry on analysis of Fig. 14 Funnel plot at 24 month follow-up using USPHS criteria. retention across subgroups. It indicates potential publication bias It represents no asymmetry on analysis across subgroups. at 18 month follow-up using FDI criteria. 0 SE(log[RR]) 0 SE(log[RR]) 0.02 0.1 0.04 0.2 0.06 0.3 0.08 0.4 RR RR 0.1 0.5 0.85 0.9 1 1.1 1.2 0.85 0.9 1 1.1 1.2 Subgroups Subgroups Retention Absence of secondary caries Retention Absence of secondary caries Absence of marginal discoloration Absence of post-operative sensitivity Absence of marginal discoloration 1.2.5 Absence of post-operative sensitivity Marginal adaptation Marginal adaptation Fig. 15 Funnel plot at 36 month follow-up using FDI criteria. Fig. 12 Funnel plot at 18 month follow-up using USPHS criteria. It represents no asymmetry on analysis across subgroups. It Represents no asymmetry on analysis across subgroups. 0 SE(log[RR]) 0 SE(log[RR]) 0.02 0.05 0.04 0.1 0.06 0.15 0.08 RR RR 0.1 0.2 0.85 0.9 1 1.1 1.2 0.85 0.9 1 1.1 1.2 Subgroups Subgroups Retention Absence of secondary caries Retention Absence of secondary caries Absence of marginal discoloration Absence of post-operative sensitivity Absence of marginal discoloration Absence of post-operative sensitivity Marginal adaptation Marginal adaptation Fig. 13 Funnel plot at 24 month follow-up using FDI criteria. Fig. 16 Funnel plot at 36 month follow-up using USPHS criteria. It represents no asymmetry on analysis across subgroups. It represents no asymmetry on analysis across subgroups. BDJ Open (2023) 9:6 K. Doshi et al. Table 3. Analysis of certainty of evidence. Table 4. GRADEpro assessment of certainty of evidence at 18 month follow-up using FDI and USPHS criteria. Follow- Evaluation criteria No. of studies up period common to both Certainty assessment № of patients Effect USPHS FDI criteria Relati Absolu Importan № of Risk Other Certainty (No. of (No. of Study Inconsiste Indirectn Imprecisi Self- Total- ve te ce studi of considerati design ncy ess on etch etch (95% (95% es bias ons studies studies CI) CI) included) included) Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Retention fewer 18 months Moderate (7) High (5) 4 RR per not publication 0.97 1000 ⨁⨁⨁◯ randomis not not 207/221 219/224 24 month Low (4) Moderate (2) 0 5 serio not serious bias strongly (0.92 (from MODERA CRITICAL ed trials serious serious (93.7%) (97.8%) us suspected to 78 TE 1.03) fewer 36 months Low (4) High (1) 1 to 29 more) Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Absence of marginal discoloration 0 fewer per Certainty of evidence RR not 1.00 randomis not not 211/215 219/223 (from ⨁⨁⨁⨁ 5 serio not serious none b (0.98 CRITICAL The certainty of evidence using GRADEpro revealed different ed trials serious serious (98.1%) (98.2%) 20 HIGH us to fewer 1.02) to 20 levels of certainty at different follow-up periods using either FDI or more) USPHS criteria (Refer Tables 3–6). Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Marginal adaptation 0 fewer per RR not 1.00 randomis not not 210/214 220/224 (from ⨁⨁⨁⨁ 5 serio not serious none (0.98 CRITICAL ed trials serious serious (98.1%) (98.2%) 20 HIGH us to DISCUSSION fewer 1.02) to 20 Clinicians have always been in a dilemma regarding the adhesive more) strategy to be used while restoring non-carious cervical lesions. Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Absence of secondary caries 0 fewer Hence, by conducting this systematic review and meta-analysis we per RR not 1.00 synthesized data from available literature on this topic to come to randomis not not 210/214 220/224 (from ⨁⨁⨁⨁ 5 serio not serious none (0.98 CRITICAL ed trials serious serious (98.1%) (98.2%) 20 HIGH us to a conclusion as to which adhesive strategy of universal adhesives fewer 1.02) to 20 more) should be employed in order to optimize clinical performances of Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Absence of post-operative sensitivity composite restorations placed in non-carious cervical lesions. 0 fewer per Since RCTs hold a high place in the level of evidence pyramid, all RR not 1.00 randomis not not 210/214 219/223 (from IMPORTA ⨁⨁⨁⨁ of the 17 studies that were included, were randomized controlled 5 serio not serious none (0.98 ed trials serious serious (98.1%) (98.2%) 20 HIGH NT us to fewer 1.02) clinical trials. to 20 more) The two most commonly used criteria for clinical evaluation are Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - total United States Public Health Service Criteria (USPHS) and the 0 fewer per RR Federation Dentaire Internationale (FDI) Criteria [42, 43]. The FDI 1000 not 1048/10 1097/11 1.00 randomis not not (from ⨁⨁⨁⨁ 25 serio not serious none 78 18 (0.99 CRITICAL ed trials serious serious 10 HIGH criteria is considered more sensitive as compared to the USPHS us (97.2%) (98.1%) to fewer 1.01) to 10 criteria [42]. Since combining the two criteria for the meta-analysis more) may introduce bias, apart from the follow-up durations, we also Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Retention decided to categorize the studies based on the criteria used for fewer RR per evaluation. 0.97 1000 ⨁⨁⨁◯ randomis serio not not 262/282 280/288 7 not serious none (0.93 (from MODERA CRITICAL ed trials us serious serious (92.9%) (97.2%) The results of our paper showed good clinical performance of to 68 TE 1.02) fewer to 19 self-etch as well as total etch strategies of universal adhesives in more) non-carious cervical lesions. There was no statistically signiﬁcant Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Absence of marginal discoloration 0 fewer difference between the two adhesive strategies in terms of per RR retention, marginal adaptation, marginal discolouration, second- 1.00 ⨁⨁⨁◯ randomis serio not not 260/266 280/284 (from 7 not serious none (0.98 MODERA CRITICAL ed trials us c serious serious (97.7%) (98.6%) 20 to TE ary caries or post-operative sensitivity at the 18th, 24th and 36th fewer 1.02) to 20 month follow-ups. However, the retention was slightly higher for more) Comparison self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Marginal adaptation the self-etch group at these follow-ups. This may be due to the fact that the total etch strategy is quite technique sensitive. more RR per publication 1.01 1000 Phosphoric acid etching could nowadays be considered too randomis serio not not 262/266 280/291 ⨁⨁◯ ◯ 7 not serious bias strongly (0.98 (from CRITICAL ed trials us serious serious (98.5%) (96.2%) LOW suspected a to 19 aggressive for dentin, given all the consequences related to 1.04) fewer to 38 exposure of the vulnerable collagen [44]. If the collagen collapses more) Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Absence of secondary caries after etching and rinsing, the resin monomers are unable to 0 fewer inﬁltrate and form resin tags and hence there is a failure of the per RR 1.00 ⨁⨁⨁◯ randomis serio not not 262/266 280/284 (from micromechanical bonding and retention of the restoration [45]. 7 not serious none (0.98 MODERA CRITICAL ed trials us c serious serious (98.5%) (98.6%) 20 to TE fewer Another reason could be the role of the 10-MDP molecule which is 1.02) to 20 more) most commonly present in universal adhesives. This molecule Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - 1.2.5 Absence of post-operative sensitivity adheres to calcium with mild decalciﬁcation of enamel and dentin 0 fewer per RR hydroxyapatite that leads to calcium release and subsequent 1.00 ⨁⨁⨁◯ randomis serio not not 260/266 274/281 (from IMPORTA 7 not serious none (0.98 MODERA ed trials us c serious serious (97.7%) (97.5%) 20 NT formation of stable self-assembled MDP-Ca salts in the form of to TE fewer 1.02) to 20 nano layering [46–48]. Hence, when used in self-etch strategy it is more) capable of providing a simultaneous chemical and micro- Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - total 0 fewer mechanical adhesion, leading to improved retention. per RR 1306/13 1394/14 1.00 ⨁⨁⨁◯ Our results are contradictory to those obtained in a previous randomis serio not not (from 35 not serious none 46 28 (0.99 MODERA CRITICAL ed trials us c serious serious 10 (97.0%) (97.6%) to TE systematic review and meta-analysis that concluded that retention fewer 1.01) to 10 more) and risk of post-operative sensitivity were both signiﬁcantly higher for the total-etch group [49]. This may be because unlike our paper, their meta-analysis combined the results for any criteria used for the clinical evaluation, which may have introduced some kind of bias. Another systematic review [50] that compared the BDJ Open (2023) 9:6 K. Doshi et al. Table 5. GRADEpro assessment of certainty of evidence at 24 month Table 6. GRADEpro assessment of certainty of evidence at 36 month follow-up using FDI and USPHS criteria. follow-up using USPHS and FDI criteria. Certainty assessment № of patients Effect Certainty assessment № of patients Effect Certainty Importance № of Study Risk Other Self- Total Relative Absolute Inconsistency Indirectness Imprecision Relativ Certaint Importanc studies design of bias considerations etch etch (95% CI) (95% CI) № of Risk Other Absolut Study Inconsistenc Indirectnes Imprecisio Self- Total e y e studie of consideration e Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Retention design y s n etch etch (95% s bias s (95% CI) CI) 30 fewer very RR 0.97 per 1000 Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Retention randomised 164/173 177/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.90 to (from 100 CRITICAL trials (94.8%) (100.0%) a 1.05) fewer to LOW 4 randomise very not serious not serious not serious none 148/154 163/163 RR 0.98 20 fewer ⨁⨁◯ ◯ CRITICAL 50 more) d trials seriou (96.1%) (100.0% (0.92 to per 1000 LOW s ) 1.05) (from 80 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Absence of marginal discoloration 50 more) 0 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Absence of marginal discoloration very RR 1.00 per 1000 randomised 164/164 177/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.98 to (from 20 CRITICAL 4 randomise very not serious not serious not serious none 147/148 162/163 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL trials (100.0%) (100.0%) a 1.02) fewer to LOW d trials seriou (99.3%) (99.4%) (0.97 to per 1000 LOW 20 more) a s 1.02) (from 30 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Marginal adaptation 20 more) 30 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Marginal adaptation very RR 0.97 per 1000 randomised 164/173 177/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.90 to (from 100 CRITICAL trials (94.8%) (100.0%) 4 randomise very not serious not serious not serious none 146/148 163/163 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL a 1.05) fewer to LOW d trials seriou (98.6%) (100.0% (0.97 to per 1000 LOW 50 more) s ) 1.02) (from 30 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Absence of secondary caries 20 more) 0 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Absence of secondary caries very RR 1.00 per 1000 randomised 162/164 176/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.97 to (from 30 CRITICAL trials (98.8%) (99.4%) 4 randomise very not serious not serious not serious none 148/148 163/163 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL a 1.02) fewer to LOW d trials seriou (100.0% (100.0% (0.98 to per 1000 LOW 20 more) s ) ) 1.02) (from 20 Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Absence of post-operative sensitivity fewer to 20 more) 0 fewer very RR 1.00 per 1000 Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Absence of post-operative sensitivity randomised 78/78 89/89 ⨁⨁◯ ◯ 2 serious not serious not serious not serious none (0.97 to (from 30 IMPORTANT trials (100.0%) (100.0%) b 1.03) fewer to LOW 3 randomise very not serious not serious not serious none 111/112 121/123 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL 30 more) d trials seriou (99.1%) (98.4%) (0.97 to per 1000 LOW s 1.03) (from 30 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - total 30 more) 0 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria – total very RR 1.00 per 1000 randomised 732/752 796/797 ⨁⨁◯ ◯ 18 serious not serious not serious not serious none (0.98 to (from 20 CRITICAL trials (97.3%) (99.9%) a LOW 4 randomise very not serious not serious not serious none 700/710 772/775 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL 1.01) fewer to 10 more) d trials seriou (98.6%) (99.6%) (0.99 to per 1000 LOW s 1.01) (from 10 Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Retention fewer to 10 more) 38 fewer RR 0.96 per 1000 randomised serious 87/96 97/103 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.89 to (from 104 CRITICAL Comparison of self-etch and total-etch strategy at 36th month under FDI - Retention trials (90.6%) (94.2%) MODERATE 1.04) fewer to 38 more) randomise not not serious not serious not serious none 40/45 44/45 RR 0.91 88 fewer ⨁⨁⨁⨁ CRITICAL 1 d trials seriou (88.9%) (97.8%) (0.81 to per 1000 HIGH Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Absence of marginal discoloration s 1.02) (from 186 fewer to 0 fewer 20 more) RR 1.00 per 1000 randomised serious 85/87 94/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.96 to (from 39 CRITICAL c Comparison of self-etch and total-etch strategy at 36th month under FDI - Absence of marginal discoloration trials (97.7%) (96.9%) MODERATE 1.05) fewer to 48 more) 1 randomise not not serious not serious not serious none 40/40 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Marginal adaptation s ) ) 1.05) (from 40 fewer to 20 fewer 50 more) RR 0.98 per 1000 randomised serious 87/89 97/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.91 to (from 90 CRITICAL trials (97.8%) (100.0%) Comparison of self-etch and total-etch strategy at 36th month under FDI - Marginal adaptation MODERATE 1.06) fewer to 60 more) 1 randomise not not serious not serious not serious none 40/40 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Absence of secondary caries s ) ) 1.05) (from 40 fewer to 0 fewer 50 more) RR 1.00 per 1000 randomised serious 89/89 97/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.97 to (from 30 CRITICAL trials (100.0%) (100.0%) MODERATE Comparison of self-etch and total-etch strategy at 36th month under FDI - Absence of secondary caries 1.03) fewer to 30 more) 1 randomise not not serious not serious not serious none 40/40 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH Comparison self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Absence of post-operative sensitivity s ) ) 1.05) (from 40 10 more fewer to RR 1.01 per 1000 50 more) randomised serious 88/88 96/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.97 to (from 30 IMPORTANT trials c (100.0%) (99.0%) 1.05) fewer to MODERATE Comparison of self-etch and total-etch strategy at 36th month under FDI - Absence of post-operative sensitivity 49 more) 1 randomise not not serious not serious not serious none 42/42 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL Comparison self-etch and total-etch adhesive strategy at 24th month under FDI criteria - total d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH s ) ) 1.05) (from 40 0 fewer fewer to RR 1.00 per 1000 randomised serious 436/449 481/491 ⨁⨁⨁◯ 50 more) 10 not serious not serious not serious none (0.98 to (from 20 CRITICAL trials c (97.1%) (98.0%) 1.02) fewer to MODERATE Comparison of self-etch and total-etch strategy at 36th month under FDI - total 20 more) 5 randomise not not serious not serious not serious none 202/207 220/221 RR 0.98 20 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (97.6%) (99.5%) (0.95 to per 1000 HIGH s 1.01) (from 50 fewer to 10 more) various adhesive strategies of universal adhesives concluded that there was no signiﬁcant difference between the total-etch and self etch strategy, although it slightly favoured the total-etch strategy in terms of retention, absence of fracture and secondary caries. The major difference between universal adhesives and tradi- Although our results obtained no signiﬁcant difference tional one-step SE adhesives is the presence of functional between the two adhesive strategies employed, it is worthwhile phosphate and/or carboxylate monomers in universal adhesives, to know that the certainty of evidence fell from high certainty (in for example 10-MDP (10-methacryloyloxydecyl dihydrogen phos- the 18th month followup under the FDI criteria) to moderate-low phate), GPDM (glycerol-phosphate dimethacrylate), PENTA (dipen- taerythritol penta acrylate monophosphate), PAC (polyalkenoic certainty in the 24 and 36 month follow-ups. There was a acid copolymer), etc. The high-quality bonding performance can difference seen in the certainty of evidence among the two be explained by the presence of the functional monomer 10-MDP criteria as well. This may be because the number of studies in most Universal adhesives. 10-MDP includes a methacrylate varied at each follow-up as well as in each evaluation criteria. polymerizable end, a long hydrophobic 10-carbon chain and a Different studies were evaluated under each criteria at every short hydrophilic phos[hate component that is capable of ionizing follow-up period. The certainty of evidence was high for the and interacting with hydroxyapatite. Apart from the ability of nano 36 month followup under the FDI criteria, but only one study layering, the presence of the long carbon chain in this molecule was included in this meta-analysis. Hence results of the longer has also been reported to contribute to the excellent bonding follow-ups must be interpreted with caution. The sensitivity ability of universal adhesives [51]. The longer chains make the analysis done after eliminating the high risk studies concluded monomer more hydrophobic, which may enhance the chemical that no signiﬁcant difference was obtained, and hence the interaction with calcium and reduce their degradation [52]. results of the meta-analysis could be considered in spite of including studies with high risk of bias (Tables 3–6). The major strength of our systematic review is that we have The funnel plot analysis revealed that there was a strong risk of evaluated the clinical performance of Universal adhesives in publication bias in the retention domain at the 18th month follow- NCCLs separately at various follow-up periods. The follow-up up under FDI criteria suggesting that the results must be period has an impact on the clinical performance of restorations interpreted with caution and cannot be generalised to a larger and hence an appropriate analysis must evaluate data from population. various studies at the same follow-up period. Another strength is BDJ Open (2023) 9:6 K. Doshi et al. that our meta-analysis evaluates data using different evaluation 14. Erhardt MCG, Cavalcante LMA, Pimenta LAF. Inﬂuence of phosphoric acid pre- treatment on self-etching bond strengths [Internet]. J Esthet Restor Dent. criteria (USPHS and FDI), separately, since both these criteria have 2004;16:33–40. Available from: https://doi.org/10.1111/j.1708- different speciﬁcations. Additionally, we used the most recently 8240.2004.tb00448.x. introduced and highly speciﬁc Cochrane’s RoB2 tool for quality 15. Rotta M, Bresciani P, Moura SK, Grande RHM, Hilgert LA, Baratieri LN, et al. Effects assessment, which was introduced in 2019. The previous version of phosphoric acid pretreatment and substitution of bonding resin on bonding had some issues with assessment of bias due to incomplete effectiveness of self-etching systems to enamel. J Adhes Dent. 2007;9:537–45. outcome data and selective reporting of outcomes causing 16. Alex G. Universal adhesives: the next evolution in adhesive dentistry? Compend particular difﬁculties, and confusion over whether studies that Contin Educ Dent. 2015;36:15–26. were not blinded should automatically be considered to be at 17. Perdigão J, Kose C, Mena-Serrano AP, De Paula EA, Tay LY, Reis A, et al. A new high risk of bias. RoB2 takes into account the risk of bias in the universal simpliﬁed adhesive: 18-month clinical evaluation [Internet]. Operative meta-analyses and review conclusions as well. Hence, it is a more Dent. 2014;39:113–27. https://doi.org/10.2341/13-045-c. 18. Hanabusa M, Mine A, Kuboki T, Momoi Y, Van Ende A, Van Meerbeek B, et al. rigorous assessment of the quality of the clinical trial. Bonding effectiveness of a new “multi-mode” adhesive to enamel and dentine. J. A major limitation of our review is the low and moderate Dent. 2012;40:475–84. certainty of evidence observed at these short and medium-term 19. 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Peumans M, De Munck J, Mine A, Van Meerbeek B. Clinical effectiveness of Hence future prospects must aim at evaluating the clinical contemporary adhesives for the restoration of non-carious cervical lesions. A performance at longer follow-up periods. This review throws light systematic review. Dent. Mater. 2014;30:1089–103. on the fact that researchers must keep in mind the latest 23. Gwinnett AJ, Kanca J 3rd. Interfacial morphology of resin composite and shiny guidelines for evaluation of risk of bias while conducting clinical erosion lesions. Am J Dent. 1992;5:315–7. trials on this subject. This will help in making higher quality 24. Tay FR, Pashley DH. Resin bonding to cervical sclerotic dentin: a review. J Dent. research available in the future. Researchers must also focus on 2004;32:173–96. maintaining longer follow-ups which would help us evaluate the 25. Higgins JPT, Savović J, Page MJ, Elbers RG, Sterne JAC Assessing risk of bias in a randomized trial [Internet]. Cochrane Handbook for Systematic Reviews of clinical performance of Universal adhesives in NCCLs in a Interventions. Wiley; 2019. p. 205–28. Available from: https:// better way. onlinelibrary.wiley.com/doi/10.1002/9781119536604.ch8. 26. Lopes LS, Calazans FS, Hidalgo R, Buitrago LL, Gutierrez F, Reis A, et al. Six-month follow-up of cervical composite restorations placed with a new universal adhe- CONCLUSION sive system: a randomized clinical trial. Oper Dent. 2016;41:465–80. In conclusion, most universal adhesives show acceptable clinical 27. de Paris Matos T, Perdigão J, de Paula E, Coppla F, Hass V, Scheffer RF, et al. Five- performance. 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Follow-up of ﬂowable resin AUTHOR CONTRIBUTIONS composites performed with a universal adhesive system in non-carious cervical KD: conceptualisation, methodology, literature search, data extraction, writing of lesions: A randomized, controlled 24-month clinical trial. Am J Dent. original draft. NMS: conceptualization, methodology, reviewing and editing draft, 2020;33:39–42. supervision, project administration. AB: Statistics and meta-analysis. PS: Literature 39. Ruschel VC, Stolf SC, Shibata S, Chung Y, Boushell LW, Baratieri LN, et al. Three- search, Data extraction, validation, supervision, project administration. DPAS: year clinical evaluation of universal adhesives in non-carious cervical lesions. Am. Reviewing and editing the draft, supervision, project administration. BJ: Reviewing J. Dent. 2019;32:223–8. and editing draft. RS: Reviewing and editing draft. 40. 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The effects Supplementary information The online version contains supplementary material of common errors on sealing ability of total-etch adhesives. Dent Mater. available at https://doi.org/10.1038/s41405-022-00124-6. 2006;22:560–8. 46. Yoshihara K, Hayakawa S, Nagaoka N, Okihara T, Yoshida Y, Van Meerbeek B. Correspondence and requests for materials should be addressed to Riluwan Etching efﬁcacy of self-etching functional monomers. J. Dent. Res. 2018;97:1010–6. Siddique. 47. Fukegawa D, Hayakawa S, Yoshida Y, Suzuki K, Osaka A, Van, et al. Chemical interaction of phosphoric acid ester with hydroxyapatite. J Dent Res. 2006;85:941–4. Reprints and permission information is available at http://www.nature.com/ 48. Yoshihara K, Yoshida Y, Nagaoka N, Fukegawa D, Hayakawa S, Mine A, et al. Nano- reprints controlled molecular interaction at adhesive interfaces for hard tissue recon- struction. Acta Biomater. 2010;6:3573–82. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims 49. Josic U, Maravic T, Mazzitelli C, Radovic I, Jacimovic J, Del Bianco F, et al. Is clinical in published maps and institutional afﬁliations. behavior of composite restorations placed in non-carious cervical lesions inﬂu- enced by the application mode of universal adhesives? A systematic review and meta-analysis. Dent Mater [Internet]. 20211; Available from: https://doi.org/ 10.1016/j.dental.2021.08.017. 50. Arbildo-Vega H, Lamas-Lara C, Cruzado-Oliva F, Rosas-Prado C, Gómez-Fuertes A, Open Access This article is licensed under a Creative Commons Vásquez-Rodrigo H. Comparison of the clinical effect of the adhesive strategies of Attribution 4.0 International License, which permits use, sharing, universal adhesives in the treatment of non-carious cervical lesions. Systematic adaptation, distribution and reproduction in any medium or format, as long as you give review and meta-analysis. Int J Oral Biol. 2018;7:210–22. appropriate credit to the original author(s) and the source, provide a link to the Creative 51. Yoshihara K, Yoshida Y, Nagaoka N, Hayakawa S, Okihara T, De Munck J, et al. Commons license, and indicate if changes were made. The images or other third party Adhesive interfacial interaction affected by different carbon-chain monomers. material in this article are included in the article’s Creative Commons license, unless Dent Mater. 2013;29:888–97. indicated otherwise in a credit line to the material. If material is not included in the 52. Feitosa VP, Sauro S, Ogliari FA, Ogliari AO, Yoshihara K, Zanchi CH, et al. Impact of article’s Creative Commons license and your intended use is not permitted by statutory hydrophilicity and length of spacer chains on the bonding of functional mono- regulation or exceeds the permitted use, you will need to obtain permission directly mers. Dent Mater. 2014;30:e317–23. from the copyright holder. To view a copy of this license, visit http:// 53. Pannuti CM, Sendyk DI, Graças YT das, Takai SL, de Paulo Aragão SABÓIA V, creativecommons.org/licenses/by/4.0/. Romito GA, et al. Clinically relevant outcomes in dental clinical trials: challenges and proposals [Internet]. Vol. 34, Brazilian Oral Research. 2020. Available from: https://doi.org/10.1590/1807-3107bor-2020.vol34.0073. © The Author(s) 2023 BDJ Open (2023) 9:6 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BDJ Open Springer Journals http://www.deepdyve.com/lp/springer-journals/effect-of-adhesive-strategy-of-universal-adhesives-in-noncarious-7jP6WyK44o

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DOI: 10.1038/s41405-022-00124-6
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Abstract

www.nature.com/bdjopen ARTICLE OPEN Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis 1 1 1 1 2 1 Krisha Doshi , M. S. Nivedhitha , Pradeep Solete , Delphine Pricilla Antony S , Arthi Balasubramaniam , Benoy Jacob and 1✉ Riluwan Siddique © The Author(s) 2023 OBJECTIVE: To determine the effect of adhesive strategy (total etch or self-etch) of universal adhesives in non-carious cervical lesions. DATA SOURCE: A search was made in PubMed, Scopus, Cochrane, Web Of Science, Open Gray, Clinical Registries. DATA SELECTION: Randomized Controlled Clinical Trials, studies on non-carious cervical lesions restored using Universal Adhesives, and studies in which universal adhesives have been used in total etch and self -etch strategies were included in this systematic review. DATA EXTRACTION: A total of 17 articles were included in the systematic review and 13 in the meta-analysis. Meta-analysis was conducted to assess the clinical performance of NCCLs in terms of retention, marginal adaptation, marginal discoloration, secondary caries and post-operative sensitivity at 18, 24, 36 month follow-up using USPHS as well as FDI criteria, separately. DATA SYNTHESIS: Overall there was no signiﬁcant difference between total etch and self etch adhesive strategies for any of the ﬁve outcome measures using either the FDI or the USPHS criteria. p > 0.05, 95% CI, I value of 0%. A strongly suspected publication bias in the retention domain was seen at 18 month follow up under FDI criteria. CONCLUSION: Most universal adhesives show acceptable clinical performance. There is no signiﬁcant effect of the adhesive strategy of universal adhesives on their clinical performance according to the results of our meta-analysis. BDJ Open (2023) 9:6 ; https://doi.org/10.1038/s41405-022-00124-6 INTRODUCTION dentin, as a result there is a decrease in bond strength [10–12]. In The advent of adhesive dentistry has revolutionized the ﬁeld of self-etch adhesive systems, the demineralization of the dental restorative dentistry. Scientiﬁc evidence shows that bonded substrates is produced by non-rinsing acidic primers mixed with restorations demonstrate an array of advantages including hydrophilic monomers such as HEMA. These primers dissolve the minimal invasion, better aesthetics, stronger bond strength, mineral component of the smear layer and alter the underlying reduced microleakage, better distribution of functional stresses superﬁcial dentin to receive the adhesive into the smear plugs and more favourable failures [1, 2]. [13]. The low bond strength and the inferior marginal adaptation Kramer and McLean in 1952 [3], were among the ﬁrst to use to the enamel are the drawbacks of self-etch adhesives when glycerophosphoric acid dimethacrylate (GPDM) to bond to dentin. compared to total-etch systems [14, 15]. They demonstrated certain alterations in the staining of dentin More recently, the introduction of Universal adhesives, also during histologic examination, that is presently known as the called multimode adhesives can be used with or without acid hybrid layer [4]. This pioneering work followed by Buonocore’s etching in both enamel and dentin [16–19]. Different researchers discovery of the acid-etch technique has led to major changes in have shown that universal adhesives have high bond strength bonding to tooth structure [5]. Over the years, dental adhesives values, and this is due to the acidic monomers that promote have progressed from three-step systems, to two-step systems chemical bonding to the tooth [18, 20]. and ﬁnally to single step systems [6]. The technique or adhesive Non-carious cervical lesions (NCCLs) are hard tissue defects in strategy has also developed from a more time-consuming and the cervical region of the teeth that are not caused by a bacterial technique sensitive total etch system to a simpler self-etch system. agent [21]. Restorations of NCCLs are common in the clinical The consensus of total-etch versus self-etch strategy for bonding setting, and represent one of the least durable restorations, with a has been widely debated over the past two decades [7–9]. high rate of retention loss, marginal discoloration and lack of The major disadvantage of the total etch system is that there is marginal adaptation. The major challenges in restoring NCCLs a risk of collagen ﬁbril collapse during drying of the demineralized include the difﬁculty in controlling moisture and obtaining access Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical And Technical Sciences (SIMATS), Chennai, Tamil Nadu, India. Department of Public Health Dentistry, Saveetha Dental College, Saveetha University, Chennai, India. email: riluwanas@gmail.com Received: 28 March 2022 Revised: 21 September 2022 Accepted: 23 September 2022 1234567890();,: K. Doshi et al. to the subgingival margins, as well as selecting the best adhesive makes the hybrid layer formation more difﬁcult on this surface strategy [22]. [23, 24]. Phosphoric acid conditioning before self-etch primers has The lack of enamel or macro-mechanical undercuts, high been suggested to improve the retention of these restorations degree of sclerosis and substantial differences in bonding surface [24]. Since, this effect has not been assessed sufﬁciently with Table 1. Search strategy. Search Engine Search strategy PubMed (((((((((((non carious cervical lesions) OR (non-carious cervical lesions)) OR (cervical abrasion)) OR (tooth abrasion)) OR (tooth erosion)) OR (cervical (27 results) lesions)) OR (NCCL)) OR (NCCLs)) OR (Class V)) OR (Class 5)) AND (((((((((((Dentin Bonding Agent) OR (Dental adhesives) OR (Universal adhesive) OR (Universal bonding agent)) OR (Multimode adhesives)) OR (Multi mode adhesives)) OR (eighth generation bonding agent)) OR (8th generation bonding agent)) OR (8th-generation bonding agent)) OR (eighth-generation bonding agent)) OR (eighth generation adhesive)) OR (8th generation adhesive))))) AND ((((((((((((Self etch) OR (self-etch)) OR (One step self etch)) OR (One-step self etch)) OR (one-step self-etch))OR (1 step self-etch)) OR (1-step self-etch)) OR (1-step self etch)) OR (self-etch technique)) OR (self-etch strategy)) OR (self-etching)) OR (self etching))) AND (((((((((total etch) OR (acid etching) OR (total-etch)) OR (etch and rinse)) OR (etch & rinse)) OR (etch-and-rinse)) OR (etch-&-rinse)) OR (total etch technique)) OR (total-etch technique)) OR (total-etching) AND ((((((((((post operative sensitivity) OR (post-operative sensitivity)) OR (postoperative sensitivity)) OR (retention)) OR (marginal adaptation)) OR (marginal discolouration)) OR (marginal staining)) OR (United States Public Health Service)) OR (FDI criteria)) OR (secondary caries)) Cochrane #1 (non-carious cervical lesions) OR (cervical abrasion) OR (cervical lesion) OR (NCCL) OR (Class V) (Word variations have been searched) (48 results) #2 MeSH descriptor: [Tooth Abrasion] this term only #3 MeSH descriptor: [Tooth Erosion] this term only #4 (Universal Adhesives) OR (Universal bonding agents) OR (Multimode adhesives) OR (Eighth generation bonding agents) OR (8th generation adhesives) (Word variations have been searched) #5 MeSH descriptor: [Dentin-Bonding Agents] this term only #6 (self etch) OR (one-step self etch) OR (Self-etching) OR (1 step self-etch) (Word variations have been searched) #7 (total etch) OR (etch and rinse) OR (etch & rinse) OR (acid etch) OR (acid etching) (Word variations have been searched) #8 MeSH descriptor: [Acid Etching, Dental] this term only #9 (FDI criteria) OR (marginal adaptation) OR (marginal discolouration) OR (“United States Public Health Service”) OR (marginal staining) (Word variations have been searched) #10 MeSH descriptor: [United States Public Health Service] this term only #11 (secondary caries) OR (retention) OR (postoperative sensitivity) OR (post-operative sensitivity) OR (post operative sensitivity) (Word variations have been searched) #12 #1 OR #2 OR #3 #13 #4 OR #5 #14 #7 OR #8 #15 #9 OR #10 OR #11 #16 #12 AND #13 AND #6 AND #14 AND #15 Scopus (TITLE-ABS-KEY (“Non-carious cervical lesion” OR “non carious cervical lesion” OR “cervical abrasion” OR “tooth abrasion” OR “tooth erosion” OR (43 results) nccl OR nccls)) AND (TITLE-ABS-KEY (“Dentin bonding agent” OR “Dental adhesive” OR “Universal Adhesive” OR “Universal bonding agent” OR “Multimode adhesive” OR “Multi mode adhesive” OR “Eighth generation adhesive” OR “8th generation adhesive” OR “Eighth generation bonding agent” OR “8th generation bonding agent”)) AND (TITLE-ABS-KEY (“self etch” OR {self-etch} OR “self etching” OR {self-etching})) AND (TITLE-ABS- KEY (“total etch” OR {total-etc} OR “total etching” OR {total-etching} OR “acid etch” OR “acid etching” OR “etch and rinse” OR {etch-and-rinse} OR “etching and rinsing” OR {etch-n-rinse})) AND (TITLE-ABS-KEY (“postoperative sensitivity” OR “post operative sensitivity” OR {post-operative sensitivity} OR retention OR “marginal adaptation” OR “marginal discolouration” OR “marginal staining” OR “secondary caries” OR “United States Public Health Service criteria” OR {USPHS criteria} OR {FDI criteria} OR “clinical evaluation” OR “clinical performance”)) Web of Science #6 (25 results) #5 AND #4 AND #3 AND #2 AND #1 Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #5 (ALL = (postoperative sensitivity OR post-operative sensitivity OR post operative sensitivity OR Retention OR secondary caries OR marginal discolouration OR marginal staining OR marginal adaptation OR United States Public Health Service OR FDI OR clinical evaluation OR clinical performance)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #4 (ALL = (self etch OR Self-etch OR self etching)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #3 (ALL = (Total etch OR total-etch OR etch and rinse OR acid etching OR total etching OR etching and rinsing)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #2 (ALL = (Universal adhesive OR universal bonding agent OR Multimode adhesive OR Multi-mode adhesive OR Eighth generation bonding agent OR 8th generation bonding agent)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years #1 (All = (Non carious cervical lesion OR Cervical abrasion OR NCCL OR tooth abrasion OR tooth erosion)) AND LANGUAGE: (English) AND DOCUMENT TYPES: (Article) Indexes=SCI-EXPANDED, CPCI-S, ESCI Timespan=All years Open Grey Universal Adhesives AND Non-Carious Cervical Lesions (0 results) BDJ Open (2023) 9:6 K. Doshi et al. universal adhesives, the aim of this systematic review was to adaptation, Marginal discolouration, Retention, Secondary caries determine the effects of adhesive strategy (total etch or self-etch) and Post-operative sensitivity. of universal adhesives in non-carious cervical lesions. The Population (P) was patients requiring restoration of non-carious cervical lesions; Intervention (I) was the use of Universal adhesive MATERIALS AND METHODS This systematic review was performed following the Preferred Reporting in Self-etch adhesive strategy; Comparison (C) was the use of Items for Systematic Reviews (PRISMA 2020) guidelines (http:// Universal adhesive in total etch adhesive strategy and the www.prisma-statement.org) and the Cochrane Handbook of Systematic Outcome (O) was clinical evaluation in terms of Marginal Reviews of Interventions (Version 6.2.0) [25]. Identification of studies via databases and registers Protocol registration The protocol for this systematic review has been registered with the Records removed before PROSPERO International prospective register of systematic reviews, registry Records identified from*: screening: Pubmed (n =27) No. CRD42021250429. Duplicate records removed Scopus (n=43) (n=49) Cochrane (n=48) Records marked as ineligible Web of Science (n=25) by automation tools (n=0) Open Grey (n=0) Selection criteria Records removed for other Registers (n=0) reasons (n=0) Only Randomized Controlled Clinical Trials (RCTs) in which non-carious cervical lesions were restored using Universal adhesives in total etch or self etch strategy were included in the systematic review. In case of studies having publications with multiple follow ups, the publication with the longest Records screened Records excluded** (n=94) (n=73) follow up only was included. In-vitro studies, or studies on cavity designs other than NCCLs were excluded from this systematic review. Studies using adhesives other than universal adhesives, or those not assessing the clinical performance in terms of marginal adaptation, marginal discoloration, Studies sought for retrieval Studies not retrieved (n=21) (n=0) retention, secondary caries or post-operative sensitivity were also excluded. Search strategy Studies assessed for eligibility Studies excluded: A detailed search was done in the following databases: Medline (PubMed), (n=21) Multiple reports of same Cochrane, Scopus, Web of Science and OpenGrey and clinical trial registry study (n=4) for the identiﬁcation of relevant studies. The search queries in the database were formulated with the basis of PICO questions in combination with various Boolean operators such as AND, OR. MeSH terms used for the search included “Dentin bonding agent”, “Dental Adhesive”, “acid etching”, Studies excluded for meta- Studies included in Systematic analysis: “tooth abrasion”, ‘tooth erosion’, “United States Public Health Service”.No Review Studies with follow-up other language restriction was applied. Related articles and the reference lists of (n=17) than 18, 24 or 36 months (n=4) the articles that were retrieved by the search engines were manually checked for possible eligibility (Table 1). Studies included in Meta- Analysis Screening process (n=13) The search and screening process was carried out by two authors (Krisha Doshi, Pradeep Solete), independently. As a ﬁrst step, titles and abstracts Fig. 1 PRISMA Flowchart. Flowchart of Included Studies according were analyzed, followed by full text analysis. An in-depth analysis of the to PRISMA guidelines. Fig. 2 Risk of Bias Graph. Graph representing each risk of bias item presented as percentages across all included studies. BDJ Open (2023) 9:6 Screening Idenﬁcaon Included K. Doshi et al. Table 2. List of excluded studies with reasons. Author/Year Reason for exclusion Mena-serrano et al. (2012) (Mena-Serrano et al. 2013) Same study as Matos et al. 2020 with different follow up (Matos et al. 2020) Jorge Perdigao et al. (2014) (Perdigão et al. 2014) Same study as Matos et al. 2020 with different follow-up (Matos et al. 2020) Loguercio et al. (2015)(Loguercio et al. 2015) Same study as Matos et al. 2020 with different follow-up(Matos et al. 2020) Ruschel et al. (2018)(Ruschel et al. 2018) Same study as Ruschel et al. 2019 with different follow-up (Ruschel et al. 2019) Lopes et al. (2016)(Lopes et al. 2016) 6 month follow-up Haak et al. (2018)(Haak et al. 2018) 6 month follow-up Manarte-Monteiro et al. (2019)(Manarte-Monteiro et al. 2019) 12 month follow-up Cruz et al. 2020(Cruz et al. 2020) 6 month follow-up articles for inclusion or exclusion was performed by the two authors separately to include in the systematic review. Any disagreement in selecting the articles between the authors was resolved by discussion with the third author (Nivedhitha M. S.), who is a senior professor. Data extraction The studies that fulﬁlled the inclusion criteria were processed for the extraction of data. The data were recorded as follows: ﬁrst author and year of publication, type of study, sample size, mean age and gender of the participants, followup period, study groups, number of teeth per group, isolation method, criteria used for clinical evaluation and clinical evaluation scores per group. The information regarding assessment of the risk of bias was also collected. The extraction of the information was done by two independent authors (Krisha Doshi, Pradeep Solete) using a standard form. Incase of any disagreement between the reviewers it was resolved by the third author (Nivedhitha M. S.), who is a senior professor. Methodological quality assessment of included studies The evaluation of the methodological quality of the included studies was assessed using the bias risk assessment tool (RoB 2), described in the Cochrane Handbook of Systematic Reviews of Interventions (Version 6.2.0) [25]. Brieﬂy, ﬁve domains were evaluated: (a) bias arising from the randomization process; (b) bias due to deviations from intended interventions; (c) bias due to missing outcome data; (d) bias in measurement of the outcome; and (e) bias in selection of the reported result. Meta-analysis The studies that had 18, 24 or 36 month follow up were included in the meta analysis. Comparison was made separately for each time interval. Meta analyses for FDI and USPHS criteria were conducted separately. - - - Akarsu et al 2020 ? + + Events of retention, marginal adaptation, absence of marginal discolora- tion, absence of secondary caries and absence of post-operative sensitivity Atalay et al 2019 - ? - + + - were analysed as dichotomized values. Since both FDI and USPHS criteria Costa et al 2020 + ? + + + ? were assessed for the above mentioned ﬁve factors, a subgroup meta- Cruz et al 2020 ? + + + + ? analysis was conducted. Estimates of intervention effects were expressed as Risk Ratios (RR) with de Albuquerque et al 2020 + + + + + + 95% conﬁdence intervals. The Mantel-Haenszel method which estimates - - Haak et al 2018 ? + + + risk ratio after adjusting for confounders was used. Heterogeneity was Kemaloglu et al 2020 + ? + - + - assessed using I statistics. Values <25% were considered as low heterogeneity, between 25% and 70% were considered as moderate Lawson et al 2015 ? + + + + ? heterogeneity, >70% were considered as high heterogeneity. Fixed effect Loguercio et al 2017 + + + + + + model was used if the I value was <40% and a random effect model was Lopes et al 2016 + + + + + + used when the I value was >40%. The signiﬁcance level was set at Manarte-Monteiro et al 2019 + - - + + - p ≤ 0.05. Publication bias for the included studies was examined by constructing Matos et al 2019 + + + + + + a funnel plot. Asymmetry of the studies in the funnel plot may reﬂect Matos et al 2020 + + + + + + publication bias. Data from the included studies were analyzed using - - - OZ et al 2019 + + + RevMan Web (Cochrane’s online review writing platform, The Cochrane Collaboration, Copenhagen, Denmark). Perdiagao et al 2019 + + + + + + Ruschel et al 2019 ? - - - + - Certainty of evidence assessment Zanatta et al 2019 + ? + + + ? Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (GRADEpro GDT software https://gradepro.org) was Fig. 3 Risk of bias summary. Graph representing the percentage of used to assess certainty of evidence from the meta-analysis which graded bias under each category assessed using Cochrane’s risk of bias evidence into very low, low, moderate or high quality. assessment tool. BDJ Open (2023) 9:6 Bias arising from the randomization process Bias due to deviations from intended interventions: Self-etch vs Total-etch Bias due to missing outcome data: Self-etch vs Total-etch Bias in measurement of the outcome: Self-etch vs Total-etch Bias in selection of the reported result: Self-etch vs Total-etch Overall bias: Self-etch vs Total-etch K. Doshi et al. Bias arising from the randomization process Bias due to deviations from intended interventions: Self-etch vs Total-etch Bias due to missing outcome data: Self-etch vs Total-etch Bias in measurement of the outcome: Self-etch vs Total-etch Bias in selection of the reported result: Self-etch vs Total-etch Overall bias: Self-etch vs Total-etch 0% 25% 50% 75% 100% Low risk of bias Some concerns High risk of bias Fig. 4 General Characteristics of included studies. Distribution of gender, adhesive, evaluation criteria, Isolation method, follow-up and Sample size among various included studies. Self-etch Total-etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 1.1.1 Retention Loguercio et al 2017 45 45 46 46 5.5% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 44 53 51 52 0.6% 0.85 [0.75 , 0.96] + + + + + + Matosetal2020 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Costa et al 2020 34 35 35 35 1.6% 0.97 [0.90 , 1.05] + ? + + + ? Subtotal (95% CI) 221 224 14.2% 0.97 [0.92 , 1.03] Total events: 207 219 Heterogeneity: Tau² = 0.00; Chi² = 11.83, df = 4 (P = 0.02); I² = 66% Test for overall effect: Z = 0.92 (P = 0.36) 1.1.2 Absence of marginal discoloration Loguercio et al 2017 43 43 46 46 5.2% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Matosetal2020 49 49 49 49 6.4% 1.00 [0.96 , 1.04] + + + + + + Costa et al 2020 35 35 35 35 3.3% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 215 223 21.6% 1.00 [0.98 , 1.02] Total events: 211 219 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 4 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 1.1.3 Marginal adaptation Loguercio et al 2017 45 45 47 47 5.6% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 34 42 38 42 0.3% 0.89 [0.75 , 1.07] + + + + + + Matosetal2020 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + Costa et al 2020 35 35 35 35 3.3% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 214 224 21.3% 1.00 [0.98 , 1.02] Total events: 206 220 Heterogeneity: Tau² = 0.00; Chi² = 3.90, df = 4 (P = 0.42); I² = 0% Test for overall effect: Z = 0.15 (P = 0.88) 1.1.4 Absence of secondary caries Loguercio et al 2017 45 45 47 47 5.6% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + Matosetal2020 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Costa et al 2020 35 35 35 35 3.3% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 214 224 21.5% 1.00 [0.98 , 1.02] Total events: 210 220 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 4 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 1.1.5 Absence of post-operative sensitivity Loguercio et al 2017 45 45 46 46 5.5% 1.00 [0.96 , 1.04] + + + + + + Matosetal2019 46 46 51 51 6.2% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.5% 1.00 [0.87 , 1.15] + + + + + + Matosetal2020 46 46 49 49 6.0% 1.00 [0.96 , 1.04] + + + + + + Costa et al 2020 35 35 3.3% 1.00 [0.95 , 1.06] 35 35 + ? + + + ? Subtotal (95% CI) 214 223 21.4% 1.00 [0.98 , 1.02] Total events: 210 219 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 4 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) Total (95% CI) 1078 1118 100.0% 1.00 [0.99 , 1.01] Total events: 1044 1097 Heterogeneity: Tau² = 0.00; Chi² = 12.47, df = 24 (P = 0.97); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.36 (P = 0.72) Self-etch Total etch Test for subgroup differences: Chi² = 0.81, df = 4 (P = 0.94), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (C) Bias due to missing outcome data: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (D) Bias in measurement of the outcome: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (E) Bias in selection of the reported result: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria (F) Overall bias: Comparison of self-etch and total-etch adhesive at 18th month under FDI criteria Fig. 5 Forest plot representing the pooled events at 18months using FDI criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 1.2.1 Retention Loguercio et al 2017 45 48 46 46 1.2% 0.94 [0.86 , 1.02] + + + + + + Matos et al 2019 46 48 51 51 1.6% 0.96 [0.89 , 1.03] + + + + + + Perdiagao et al 2019 22 25 27 27 0.3% 0.88 [0.75 , 1.03] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - - - ? + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 12 20 16 20 0.0% 0.75 [0.49 , 1.14] - ? + - + - Subtotal (95% CI) 282 288 14.6% 0.97 [0.93 , 1.02] Total events: 262 280 Heterogeneity: Tau² = 0.00; Chi² = 13.21, df = 6 (P = 0.04); I² = 55% Test for overall effect: Z = 1.25 (P = 0.21) 1.2.2 Absence of marginal discoloration Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Perdiagao et al 2019 20 22 27 27 0.4% 0.91 [0.78 , 1.06] + + + + + + Matos et al 2019 46 46 51 51 5.1% 1.00 [0.96 , 1.04] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - ? - + + - Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Akarsu et al 2020 12 12 16 16 0.4% 1.00 [0.87 , 1.15] - ? + - + - Subtotal (95% CI) 266 284 21.9% 1.00 [0.98 , 1.02] Total events: 260 280 Heterogeneity: Tau² = 0.00; Chi² = 2.04, df = 6 (P = 0.92); I² = 0% Test for overall effect: Z = 0.16 (P = 0.87) 1.2.3 Marginal adaptation Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Matos et al 2019 46 46 58 0.8% 1.13 [1.02 , 1.25] 51 + + + + + + Perdiagao et al 2019 22 22 27 27 1.3% 1.00 [0.92 , 1.08] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - - - ? + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 12 12 16 16 0.4% 1.00 [0.87 , 1.15] - ? + - + - Subtotal (95% CI) 266 291 18.5% 1.01 [0.98 , 1.04] Total events: 262 280 Heterogeneity: Tau² = 0.00; Chi² = 8.09, df = 6 (P = 0.23); I² = 26% Test for overall effect: Z = 0.57 (P = 0.57) 1.2.4 Absence of secondary caries Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Matos et al 2019 46 46 51 51 5.1% 1.00 [0.96 , 1.04] + + + + + + Perdiagao et al 2019 22 22 27 27 1.3% 1.00 [0.92 , 1.08] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - ? - + + - de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 49 49 4.9% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 12 12 16 16 0.4% 1.00 [0.87 , 1.15] - ? + - + - Subtotal (95% CI) 266 284 22.8% 1.00 [0.98 , 1.02] Total events: 262 280 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 6 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 1.2.5 1.2.5 Absence of post-operative sensitivity Loguercio et al 2017 45 45 46 46 4.5% 1.00 [0.96 , 1.04] + + + + + + Perdiagao et al 2019 22 22 27 1.3% 27 1.00 [0.92 , 1.08] + + + + + + Matos et al 2019 46 46 51 51 5.1% 1.00 [0.96 , 1.04] + + + + + + Atalay et al 2019 53 53 53 53 6.1% 1.00 [0.96 , 1.04] - - - ? + + de Albuquerque et al 2020 38 42 38 42 0.4% 1.00 [0.87 , 1.15] + + + + + + Matos et al 2020 46 46 46 46 4.6% 1.00 [0.96 , 1.04] + + + + + + Akarsu et al 2020 10 12 13 16 0.1% 1.03 [0.73 , 1.45] - ? + - + - Subtotal (95% CI) 266 281 22.2% 1.00 [0.98 , 1.02] Total events: 260 274 Heterogeneity: Tau² = 0.00; Chi² = 0.03, df = 6 (P = 1.00); I² = 0% Test for overall effect: Z = 0.01 (P = 0.99) Total (95% CI) 1346 1428 100.0% 1.00 [0.99 , 1.01] Total events: 1306 1394 Heterogeneity: Tau² = 0.00; Chi² = 16.21, df = 34 (P = 1.00); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.29 (P = 0.77) Self-etch Total-etch Test for subgroup differences: Chi² = 1.89, df = 4 (P = 0.76), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (C) Bias due to missing outcome data: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (D) Bias in measurement of the outcome: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (E) Bias in selection of the reported result: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria (F) Overall bias: Comparison of self-etch and total etch adhesive at 18th month under USPHS criteria Fig. 6 Forest plot representing the pooled events at 18 months using USPHS criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. RESULTS In these cases, the article with the richest information (longest Search and selection follow-up) was chosen and included in this review. Hence a total Study selection and exclusion is depicted in Fig. 1 and Table 2. of 17 articles were included in the qualitative analysis. 13 of the 17 Some studies reported multiple reports with different follow-ups. included articles had a follow up of either 18, 24 or 36 months and BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 2.2.1 Retention Zanatta et al (2019) 55 60 63 68 2.6% 0.99 [0.89 , 1.10] - - - + + + Costa et al (2020) 32 36 34 35 1.6% 0.92 [0.80 , 1.04] + ? + + + ? Subtotal (95% CI) 96 103 4.3% 0.96 [0.89 , 1.04] Total events: 87 97 Heterogeneity: Tau² = 0.00; Chi² = 0.88, df = 1 (P = 0.35); I² = 0% Test for overall effect: Z = 1.00 (P = 0.32) 2.2.2 Absence of marginal discoloration Zanatta et al (2019) 51 53 60 63 4.6% 1.01 [0.94 , 1.09] + - - + + - Costa et al (2020) 34 34 34 34 8.5% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 87 97 13.1% 1.00 [0.96 , 1.05] Total events: 85 94 Heterogeneity: Tau² = 0.00; Chi² = 0.06, df = 1 (P = 0.81); I² = 0% Test for overall effect: Z = 0.16 (P = 0.88) 2.2.3 Marginal adaptation Zanatta et al (2019) 55 55 63 63 24.9% 1.00 [0.97 , 1.03] + - - + + - Costa et al (2020) 32 34 34 34 2.7% 0.94 [0.85 , 1.04] + ? + + + ? Subtotal (95% CI) 89 97 27.6% 0.98 [0.91 , 1.06] Total events: 87 97 Heterogeneity: Tau² = 0.00; Chi² = 2.19, df = 1 (P = 0.14); I² = 54% Test for overall effect: Z = 0.51 (P = 0.61) 2.2.4 Absence of secondary caries Zanatta et al (2019) 55 55 63 63 24.9% 1.00 [0.97 , 1.03] - - - + + + Costa et al (2020) 34 34 34 34 8.5% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 89 97 33.4% 1.00 [0.97 , 1.03] Total events: 89 97 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 2.2.5 Absence of post-operative sensitivity Zanatta et al (2019) 54 54 62 63 13.0% 1.01 [0.97 , 1.06] + - - + + - Costa et al (2020) 34 34 34 34 8.5% 1.00 [0.95 , 1.06] + ? + + + ? Subtotal (95% CI) 88 97 21.6% 1.01 [0.97 , 1.05] Total events: 88 96 Heterogeneity: Tau² = 0.00; Chi² = 0.16, df = 1 (P = 0.69); I² = 0% Test for overall effect: Z = 0.49 (P = 0.63) Total (95% CI) 449 491 100.0% 1.00 [0.98 , 1.02] Total events: 436 481 Heterogeneity: Tau² = 0.00; Chi² = 4.59, df = 9 (P = 0.87); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.12 (P = 0.91) Self-etch Total etch Test for subgroup differences: Chi² = 1.52, df = 4 (P = 0.82), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 24th month under FDI criteria (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 24th month under FDI criteria (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 24th month under FDI criteria (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 24th month under FDI criteria (F) Overall bias: Comparison of self-etching and conventional at 24th month under FDI criteria Fig. 7 Forest plot representing the pooled events at 24 months using FDI criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. were included in the meta-analysis. Sub-group analysis was retraction cord as the choice of isolation method. The follow-up performed at each of the follow-up periods (18, 24 and 36 months), period ranged from 6 months to 5 years with maximum studies separately. lying in the range of 18–36 months. Most of the available literature did not purely compare the two Study characteristics adhesive strategies—self-etch and total-etch. They usually The study characteristics of the included studies are presented in included one or more interventions. Some of these interventions online Supplementary Table 1 and Fig. 2. A total of 2622 teeth included comparison between dry dentin and moist dentin [MD9] were evaluated from 596 patients. 687 restorations were within the total-etch group [26–28]; selective enamel etch evaluated in the self-etch group while 696 restorations were adhesive strategy [26, 27, 29–31]; effect of dentine roughness evaluated in the total-etch group. The age of the patients ranged [32]; use of optical coherence tomography for evaluation of from 20 to 60 years. 273 of the patients were males wile 256 were quality of restorations [33]; addition of copper into the adhesive females. Scotchbond Universal and Single Bond Universal were [34]; comparison with self-etch and total-etch adhesives the most commonly used adhesives. 17 studies used either USPHS [30, 31, 35]; effect of diode laser [36]; and catechin-based dentin or FDI or both criteria for evaluation of the restorations. An equal pretreatment [37]. Only relevant data pertaining to this review was number of studies used rubber dam and cotton rolls with gingival collected from these articles. BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 2.1.1 Retention Lawson et al 2015 36 36 38 38 5.5% 1.00 [0.95 , 1.05] ? + + + + ? OZ et al 2019 25 34 36 36 0.6% 0.74 [0.60 , 0.91] + - - + + - Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 173 177 21.1% 0.97 [0.90 , 1.05] Total events: 164 177 Heterogeneity: Tau² = 0.00; Chi² = 25.61, df = 3 (P < 0.0001); I² = 88% Test for overall effect: Z = 0.77 (P = 0.44) 2.1.2 Absence of marginal discoloration Lawson et al 2015 36 36 38 38 5.5% 1.00 [0.95 , 1.05] ? + + + + ? OZ et al 2019 25 25 36 36 4.2% 1.00 [0.94 , 1.07] + - - + + - Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 164 177 24.6% 1.00 [0.98 , 1.02] Total events: 164 177 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 3 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 2.1.3 Marginal adaptation Lawson et al 2015 36 36 38 38 5.5% 1.00 [0.95 , 1.05] ? + + + + ? Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - OZ et al 2019 25 34 36 36 0.6% 0.74 [0.60 , 0.91] + - - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 173 177 21.1% 0.97 [0.90 , 1.05] Total events: 164 177 Heterogeneity: Tau² = 0.00; Chi² = 25.61, df = 3 (P < 0.0001); I² = 88% Test for overall effect: Z = 0.77 (P = 0.44) 2.1.4 Absence of secondary caries Lawson et al 2015 34 36 37 38 2.4% 0.97 [0.88 , 1.07] ? + + + + ? Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - ? - + + - OZ et al 2019 25 25 36 36 4.2% 1.00 [0.94 , 1.07] + - - + + - Kemaloglu et al 2020 50 50 50 50 7.3% 1.00 [0.96 , 1.04] - - + ? + + Subtotal (95% CI) 164 177 21.5% 1.00 [0.97 , 1.02] Total events: 162 176 Heterogeneity: Tau² = 0.00; Chi² = 0.51, df = 3 (P = 0.92); I² = 0% Test for overall effect: Z = 0.16 (P = 0.87) 2.1.5 Absence of post-operative sensitivity Atalay et al 2019 53 53 53 53 7.6% 1.00 [0.96 , 1.04] - - - ? + + OZ et al 2019 25 25 36 36 4.2% 1.00 [0.94 , 1.07] + - - + + - Subtotal (95% CI) 78 89 11.8% 1.00 [0.97 , 1.03] Total events: 78 89 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) Total (95% CI) 752 797 100.0% 1.00 [0.98 , 1.01] Total events: 732 796 Heterogeneity: Tau² = 0.00; Chi² = 34.63, df = 17 (P = 0.007); I² = 51% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.53 (P = 0.60) Self-etch Total-etch Test for subgroup differences: Chi² = 1.06, df = 4 (P = 0.90), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 24th month under USPHS criteria (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 24th month under USPHS criteria (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 24th month under USPHS criteria (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 24th month under USPHS criteria (F) Overall bias: Comparison of self-etching and conventional at 24th month under USPHS criteria Fig. 8 Forest plot representing the pooled events at 24 months using USPHS criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. Methodological quality assessment of included studies [29–31, 33, 36, 38, 39] out of 17 included articles had a high Theresult ofthe qualityassessment ofRCTsofthe systematic risk of bias, 4 [9, 35, 37, 40] studies showed some concerns and 6 review is presented as risk of bias summary and risk of bias [26–28, 32, 34, 41] studies had a low risk of bias. In speciﬁc, the graph (Figs. 3, 4). As evaluated by the RoB2 tool, 7 highest risk was seen in the bias due to deviation from the BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI A B C D E F 3.2.1 Retention Matos et al 2020 40 45 44 45 20.5% 0.91 [0.81 , 1.02] + + + + + + Subtotal (95% CI) 45 45 20.5% 0.91 [0.81 , 1.02] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 1.66 (P = 0.10) 3.2.2 Absence of marginal discoloration Matos et al 2020 40 40 44 44 19.8% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 40 44 19.8% 1.00 [0.96 , 1.05] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) 3.2.3 Marginal adaptation Matos et al 2020 40 40 44 44 19.8% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 40 44 19.8% 1.00 [0.96 , 1.05] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) 3.2.4 Absence of secondary caries Matos et al 2020 40 40 44 44 19.8% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 40 44 19.8% 1.00 [0.96 , 1.05] Total events: 40 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) 3.2.5 Absence of post-operative sensitivity Matos et al 2020 42 42 44 44 20.2% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 42 44 20.2% 1.00 [0.96 , 1.05] Total events: 42 44 Heterogeneity: Not applicable Test for overall effect: Z = 0.00 (P = 1.00) Total (95% CI) 207 221 100.0% 0.98 [0.95 , 1.01] Total events: 202 220 Heterogeneity: Chi² = 4.38, df = 4 (P = 0.36); I² = 9% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 1.28 (P = 0.20) Self-etch Total-etch Test for subgroup differences: Chi² = 2.66, df = 4 (P = 0.62), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 36th month under FDI (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 36th month under FDI (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 36th month under FDI (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 36th month under FDI (F) Overall bias: Comparison of self-etching and conventional at 36th month under FDI Fig. 9 Forest plot representing the pooled events at 36 months using FDI criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. intended interventions domain with 3 studies [30, 31, 39]athigh Subgroup analysis. The outcome of retention, although insignif- risk and 5 studies [29, 35–38] showing some concerns. In the icant, slightly favoured the self-etch strategy at each follow-up for randomization and allocation concealment domain, 2 studies both the FDI and the USPHS criteria. [29, 36] showed a high risk of bias while 4 studies [9, 33, 39, 40] The outcome of marginal discolouration showed no difference showed some concerns. 4 studies [29–31, 39] showed a high risk between the two adhesive strategies at any follow-up period for of bias due to missing data and measurement of outcome any criteria. assessment. All studies showed a low risk of bias in selection of The outcome of marginal adaptation, although insigniﬁcant, reported results. showed a slight favour towards the self-etch adhesive strategy at the 24 month follow-up for both the criteria. The 36 month follow- Meta-analyses up showed no difference between the two adhesive strategies. A total of thirteen studies which compared self-etch and the total The outcome of secondary caries showed no difference between etch adhesive strategy using FDI and USPHS criteria were included the two adhesive strategies at any follow-up period for any criteria. in the meta analysis. The forest plot was produced according to The outcome of post-operative sensitivity showed no difference the FDI and USPHS criteria for the ﬁve outcome measures. between the two adhesive strategies at any follow-up period for any criteria. Group analysis. Overall there was no signiﬁcant difference between total etch and self- etch adhesive strategies using either Sensitivity analysis. A sensitivity analysis was also done by the FDI or the USPHS criteria. (p > 0.05, 95% CI, I value of 0%) at eliminating the studies with a high risk of bias. No signiﬁcant 18, 24 or 36 months. (Figs. 5–10) difference was observed in the meta-analysis. BDJ Open (2023) 9:6 K. Doshi et al. Self-etch Total-etch Risk ratio Risk ratio Risk of Bias Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F 3.1.1 Retention Perdiagao et al 2019 19 25 27 27 0.3% 0.76 [0.61 , 0.96] + + + + + + Atalay et al 2019 53 53 53 53 10.0% 1.00 [0.96 , 1.04] - ? - + + - Ruschel et al 2019 36 36 39 39 5.0% 1.00 [0.95 , 1.05] ? - - - + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 154 163 21.5% 0.98 [0.92 , 1.05] Total events: 148 163 Heterogeneity: Tau² = 0.00; Chi² = 13.69, df = 3 (P = 0.003); I² = 78% Test for overall effect: Z = 0.53 (P = 0.60) 3.1.2 Absence of marginal discoloration Perdiagao et al 2019 19 19 26 27 1.0% 1.03 [0.92 , 1.15] + + + + + + Atalay et al 2019 53 53 53 53 10.0% 1.00 [0.96 , 1.04] - - - ? + + Ruschel et al 2019 35 36 39 39 2.4% 0.97 [0.90 , 1.05] ? - - - + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 148 163 19.6% 1.00 [0.97 , 1.02] Total events: 147 162 Heterogeneity: Tau² = 0.00; Chi² = 0.82, df = 3 (P = 0.84); I² = 0% Test for overall effect: Z = 0.14 (P = 0.89) 3.1.3 Marginal adaptation Perdiagao et al 2019 19 19 27 27 1.8% 1.00 [0.92 , 1.09] + + + + + + Atalay et al 2019 53 53 53 53 10.0% 1.00 [0.96 , 1.04] - ? - + + - Ruschel et al 2019 34 36 39 39 1.5% 0.94 [0.86 , 1.04] - - - - ? + Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 148 163 19.5% 1.00 [0.97 , 1.02] Total events: 146 163 Heterogeneity: Tau² = 0.00; Chi² = 1.81, df = 3 (P = 0.61); I² = 0% Test for overall effect: Z = 0.34 (P = 0.74) 3.1.4 Absence of secondary caries Perdiagao et al 2019 19 19 27 27 1.8% 1.00 [0.92 , 1.09] + + + + + + Atalay et al 2019 53 53 52 52 9.8% 1.00 [0.96 , 1.04] - - - ? + + Ruschel et al 2019 36 36 39 39 5.0% 1.00 [0.95 , 1.05] ? - - - + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 148 162 22.8% 1.00 [0.98 , 1.02] Total events: 148 162 Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 3 (P = 1.00); I² = 0% Test for overall effect: Z = 0.00 (P = 1.00) 3.1.5 Absence of post-operative sensitivity Perdiagao et al 2019 18 19 25 27 0.6% 1.02 [0.88 , 1.19] + + + + + + Atalay et al 2019 53 53 52 52 9.8% 1.00 [0.96 , 1.04] - ? - + + - Matos et al 2020 40 40 44 44 6.3% 1.00 [0.96 , 1.05] + + + + + + Subtotal (95% CI) 112 123 16.6% 1.00 [0.97 , 1.03] Total events: 111 121 Heterogeneity: Tau² = 0.00; Chi² = 0.14, df = 2 (P = 0.93); I² = 0% Test for overall effect: Z = 0.06 (P = 0.96) Total (95% CI) 710 774 100.0% 1.00 [0.99 , 1.01] Total events: 700 771 Heterogeneity: Tau² = 0.00; Chi² = 10.25, df = 18 (P = 0.92); I² = 0% 0.85 0.9 1 1.1 1.2 Test for overall effect: Z = 0.31 (P = 0.76) Self-etch Total-etch Test for subgroup differences: Chi² = 0.31, df = 4 (P = 0.99), I² = 0% Risk of bias legend (A) Bias arising from the randomization process (B) Bias due to deviations from intended interventions: Comparison of self-etching and conventional at 36th month under USPHS criteria (C) Bias due to missing outcome data: Comparison of self-etching and conventional at 36th month under USPHS criteria (D) Bias in measurement of the outcome: Comparison of self-etching and conventional at 36th month under USPHS criteria (E) Bias in selection of the reported result: Comparison of self-etching and conventional at 36th month under USPHS criteria (F) Overall bias: Comparison of self-etching and conventional at 36th month under USPHS criteria Fig. 10 Forest plot representing the pooled events at 36 months using USPHS criteria. No signiﬁcant difference observed between total etch and self-etch adhesive strategies for any of the parameters. Publication bias publication bias in the retention domain (Fig. 11). The funnel plot for comparison of self-etch and total-etch at However, the other domains showed no publication bias 18 month under FDI criteria revealed strongly suspected (Figs. 12–16). BDJ Open (2023) 9:6 K. Doshi et al. 0 SE(log[RR]) 0 SE(log[RR]) 0.02 0.05 0.04 0.1 0.06 0.15 0.08 RR RR 0.1 0.2 0.85 0.9 1 1.1 1.2 0.85 0.9 1 1.1 1.2 Subgroups Subgroups Retention Absence of secondary caries Retention Absence of secondary caries Absence of marginal discoloration Absence of post-operative sensitivity Absence of marginal discoloration Absence of post-operative sensitivity Marginal adaptation Marginal adaptation Fig. 11 Funnel plot representing asymmetry on analysis of Fig. 14 Funnel plot at 24 month follow-up using USPHS criteria. retention across subgroups. It indicates potential publication bias It represents no asymmetry on analysis across subgroups. at 18 month follow-up using FDI criteria. 0 SE(log[RR]) 0 SE(log[RR]) 0.02 0.1 0.04 0.2 0.06 0.3 0.08 0.4 RR RR 0.1 0.5 0.85 0.9 1 1.1 1.2 0.85 0.9 1 1.1 1.2 Subgroups Subgroups Retention Absence of secondary caries Retention Absence of secondary caries Absence of marginal discoloration Absence of post-operative sensitivity Absence of marginal discoloration 1.2.5 Absence of post-operative sensitivity Marginal adaptation Marginal adaptation Fig. 15 Funnel plot at 36 month follow-up using FDI criteria. Fig. 12 Funnel plot at 18 month follow-up using USPHS criteria. It represents no asymmetry on analysis across subgroups. It Represents no asymmetry on analysis across subgroups. 0 SE(log[RR]) 0 SE(log[RR]) 0.02 0.05 0.04 0.1 0.06 0.15 0.08 RR RR 0.1 0.2 0.85 0.9 1 1.1 1.2 0.85 0.9 1 1.1 1.2 Subgroups Subgroups Retention Absence of secondary caries Retention Absence of secondary caries Absence of marginal discoloration Absence of post-operative sensitivity Absence of marginal discoloration Absence of post-operative sensitivity Marginal adaptation Marginal adaptation Fig. 13 Funnel plot at 24 month follow-up using FDI criteria. Fig. 16 Funnel plot at 36 month follow-up using USPHS criteria. It represents no asymmetry on analysis across subgroups. It represents no asymmetry on analysis across subgroups. BDJ Open (2023) 9:6 K. Doshi et al. Table 3. Analysis of certainty of evidence. Table 4. GRADEpro assessment of certainty of evidence at 18 month follow-up using FDI and USPHS criteria. Follow- Evaluation criteria No. of studies up period common to both Certainty assessment № of patients Effect USPHS FDI criteria Relati Absolu Importan № of Risk Other Certainty (No. of (No. of Study Inconsiste Indirectn Imprecisi Self- Total- ve te ce studi of considerati design ncy ess on etch etch (95% (95% es bias ons studies studies CI) CI) included) included) Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Retention fewer 18 months Moderate (7) High (5) 4 RR per not publication 0.97 1000 ⨁⨁⨁◯ randomis not not 207/221 219/224 24 month Low (4) Moderate (2) 0 5 serio not serious bias strongly (0.92 (from MODERA CRITICAL ed trials serious serious (93.7%) (97.8%) us suspected to 78 TE 1.03) fewer 36 months Low (4) High (1) 1 to 29 more) Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Absence of marginal discoloration 0 fewer per Certainty of evidence RR not 1.00 randomis not not 211/215 219/223 (from ⨁⨁⨁⨁ 5 serio not serious none b (0.98 CRITICAL The certainty of evidence using GRADEpro revealed different ed trials serious serious (98.1%) (98.2%) 20 HIGH us to fewer 1.02) to 20 levels of certainty at different follow-up periods using either FDI or more) USPHS criteria (Refer Tables 3–6). Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Marginal adaptation 0 fewer per RR not 1.00 randomis not not 210/214 220/224 (from ⨁⨁⨁⨁ 5 serio not serious none (0.98 CRITICAL ed trials serious serious (98.1%) (98.2%) 20 HIGH us to DISCUSSION fewer 1.02) to 20 Clinicians have always been in a dilemma regarding the adhesive more) strategy to be used while restoring non-carious cervical lesions. Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Absence of secondary caries 0 fewer Hence, by conducting this systematic review and meta-analysis we per RR not 1.00 synthesized data from available literature on this topic to come to randomis not not 210/214 220/224 (from ⨁⨁⨁⨁ 5 serio not serious none (0.98 CRITICAL ed trials serious serious (98.1%) (98.2%) 20 HIGH us to a conclusion as to which adhesive strategy of universal adhesives fewer 1.02) to 20 more) should be employed in order to optimize clinical performances of Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - Absence of post-operative sensitivity composite restorations placed in non-carious cervical lesions. 0 fewer per Since RCTs hold a high place in the level of evidence pyramid, all RR not 1.00 randomis not not 210/214 219/223 (from IMPORTA ⨁⨁⨁⨁ of the 17 studies that were included, were randomized controlled 5 serio not serious none (0.98 ed trials serious serious (98.1%) (98.2%) 20 HIGH NT us to fewer 1.02) clinical trials. to 20 more) The two most commonly used criteria for clinical evaluation are Comparison of self-etch and total-etch adhesive strategy at 18th month under FDI criteria - total United States Public Health Service Criteria (USPHS) and the 0 fewer per RR Federation Dentaire Internationale (FDI) Criteria [42, 43]. The FDI 1000 not 1048/10 1097/11 1.00 randomis not not (from ⨁⨁⨁⨁ 25 serio not serious none 78 18 (0.99 CRITICAL ed trials serious serious 10 HIGH criteria is considered more sensitive as compared to the USPHS us (97.2%) (98.1%) to fewer 1.01) to 10 criteria [42]. Since combining the two criteria for the meta-analysis more) may introduce bias, apart from the follow-up durations, we also Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Retention decided to categorize the studies based on the criteria used for fewer RR per evaluation. 0.97 1000 ⨁⨁⨁◯ randomis serio not not 262/282 280/288 7 not serious none (0.93 (from MODERA CRITICAL ed trials us serious serious (92.9%) (97.2%) The results of our paper showed good clinical performance of to 68 TE 1.02) fewer to 19 self-etch as well as total etch strategies of universal adhesives in more) non-carious cervical lesions. There was no statistically signiﬁcant Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Absence of marginal discoloration 0 fewer difference between the two adhesive strategies in terms of per RR retention, marginal adaptation, marginal discolouration, second- 1.00 ⨁⨁⨁◯ randomis serio not not 260/266 280/284 (from 7 not serious none (0.98 MODERA CRITICAL ed trials us c serious serious (97.7%) (98.6%) 20 to TE ary caries or post-operative sensitivity at the 18th, 24th and 36th fewer 1.02) to 20 month follow-ups. However, the retention was slightly higher for more) Comparison self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Marginal adaptation the self-etch group at these follow-ups. This may be due to the fact that the total etch strategy is quite technique sensitive. more RR per publication 1.01 1000 Phosphoric acid etching could nowadays be considered too randomis serio not not 262/266 280/291 ⨁⨁◯ ◯ 7 not serious bias strongly (0.98 (from CRITICAL ed trials us serious serious (98.5%) (96.2%) LOW suspected a to 19 aggressive for dentin, given all the consequences related to 1.04) fewer to 38 exposure of the vulnerable collagen [44]. If the collagen collapses more) Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - Absence of secondary caries after etching and rinsing, the resin monomers are unable to 0 fewer inﬁltrate and form resin tags and hence there is a failure of the per RR 1.00 ⨁⨁⨁◯ randomis serio not not 262/266 280/284 (from micromechanical bonding and retention of the restoration [45]. 7 not serious none (0.98 MODERA CRITICAL ed trials us c serious serious (98.5%) (98.6%) 20 to TE fewer Another reason could be the role of the 10-MDP molecule which is 1.02) to 20 more) most commonly present in universal adhesives. This molecule Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - 1.2.5 Absence of post-operative sensitivity adheres to calcium with mild decalciﬁcation of enamel and dentin 0 fewer per RR hydroxyapatite that leads to calcium release and subsequent 1.00 ⨁⨁⨁◯ randomis serio not not 260/266 274/281 (from IMPORTA 7 not serious none (0.98 MODERA ed trials us c serious serious (97.7%) (97.5%) 20 NT formation of stable self-assembled MDP-Ca salts in the form of to TE fewer 1.02) to 20 nano layering [46–48]. Hence, when used in self-etch strategy it is more) capable of providing a simultaneous chemical and micro- Comparison of self-etch and total-etch adhesive strategy at 18th month under USPHS criteria - total 0 fewer mechanical adhesion, leading to improved retention. per RR 1306/13 1394/14 1.00 ⨁⨁⨁◯ Our results are contradictory to those obtained in a previous randomis serio not not (from 35 not serious none 46 28 (0.99 MODERA CRITICAL ed trials us c serious serious 10 (97.0%) (97.6%) to TE systematic review and meta-analysis that concluded that retention fewer 1.01) to 10 more) and risk of post-operative sensitivity were both signiﬁcantly higher for the total-etch group [49]. This may be because unlike our paper, their meta-analysis combined the results for any criteria used for the clinical evaluation, which may have introduced some kind of bias. Another systematic review [50] that compared the BDJ Open (2023) 9:6 K. Doshi et al. Table 5. GRADEpro assessment of certainty of evidence at 24 month Table 6. GRADEpro assessment of certainty of evidence at 36 month follow-up using FDI and USPHS criteria. follow-up using USPHS and FDI criteria. Certainty assessment № of patients Effect Certainty assessment № of patients Effect Certainty Importance № of Study Risk Other Self- Total Relative Absolute Inconsistency Indirectness Imprecision Relativ Certaint Importanc studies design of bias considerations etch etch (95% CI) (95% CI) № of Risk Other Absolut Study Inconsistenc Indirectnes Imprecisio Self- Total e y e studie of consideration e Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Retention design y s n etch etch (95% s bias s (95% CI) CI) 30 fewer very RR 0.97 per 1000 Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Retention randomised 164/173 177/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.90 to (from 100 CRITICAL trials (94.8%) (100.0%) a 1.05) fewer to LOW 4 randomise very not serious not serious not serious none 148/154 163/163 RR 0.98 20 fewer ⨁⨁◯ ◯ CRITICAL 50 more) d trials seriou (96.1%) (100.0% (0.92 to per 1000 LOW s ) 1.05) (from 80 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Absence of marginal discoloration 50 more) 0 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Absence of marginal discoloration very RR 1.00 per 1000 randomised 164/164 177/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.98 to (from 20 CRITICAL 4 randomise very not serious not serious not serious none 147/148 162/163 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL trials (100.0%) (100.0%) a 1.02) fewer to LOW d trials seriou (99.3%) (99.4%) (0.97 to per 1000 LOW 20 more) a s 1.02) (from 30 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Marginal adaptation 20 more) 30 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Marginal adaptation very RR 0.97 per 1000 randomised 164/173 177/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.90 to (from 100 CRITICAL trials (94.8%) (100.0%) 4 randomise very not serious not serious not serious none 146/148 163/163 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL a 1.05) fewer to LOW d trials seriou (98.6%) (100.0% (0.97 to per 1000 LOW 50 more) s ) 1.02) (from 30 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Absence of secondary caries 20 more) 0 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Absence of secondary caries very RR 1.00 per 1000 randomised 162/164 176/177 ⨁⨁◯ ◯ 4 serious not serious not serious not serious none (0.97 to (from 30 CRITICAL trials (98.8%) (99.4%) 4 randomise very not serious not serious not serious none 148/148 163/163 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL a 1.02) fewer to LOW d trials seriou (100.0% (100.0% (0.98 to per 1000 LOW 20 more) s ) ) 1.02) (from 20 Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - Absence of post-operative sensitivity fewer to 20 more) 0 fewer very RR 1.00 per 1000 Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria - Absence of post-operative sensitivity randomised 78/78 89/89 ⨁⨁◯ ◯ 2 serious not serious not serious not serious none (0.97 to (from 30 IMPORTANT trials (100.0%) (100.0%) b 1.03) fewer to LOW 3 randomise very not serious not serious not serious none 111/112 121/123 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL 30 more) d trials seriou (99.1%) (98.4%) (0.97 to per 1000 LOW s 1.03) (from 30 fewer to Comparison of self-etch and total-etch adhesive strategy at 24th month under USPHS criteria - total 30 more) 0 fewer Comparison of self-etch and total-etch strategy at 36th month under USPHS criteria – total very RR 1.00 per 1000 randomised 732/752 796/797 ⨁⨁◯ ◯ 18 serious not serious not serious not serious none (0.98 to (from 20 CRITICAL trials (97.3%) (99.9%) a LOW 4 randomise very not serious not serious not serious none 700/710 772/775 RR 1.00 0 fewer ⨁⨁◯ ◯ CRITICAL 1.01) fewer to 10 more) d trials seriou (98.6%) (99.6%) (0.99 to per 1000 LOW s 1.01) (from 10 Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Retention fewer to 10 more) 38 fewer RR 0.96 per 1000 randomised serious 87/96 97/103 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.89 to (from 104 CRITICAL Comparison of self-etch and total-etch strategy at 36th month under FDI - Retention trials (90.6%) (94.2%) MODERATE 1.04) fewer to 38 more) randomise not not serious not serious not serious none 40/45 44/45 RR 0.91 88 fewer ⨁⨁⨁⨁ CRITICAL 1 d trials seriou (88.9%) (97.8%) (0.81 to per 1000 HIGH Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Absence of marginal discoloration s 1.02) (from 186 fewer to 0 fewer 20 more) RR 1.00 per 1000 randomised serious 85/87 94/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.96 to (from 39 CRITICAL c Comparison of self-etch and total-etch strategy at 36th month under FDI - Absence of marginal discoloration trials (97.7%) (96.9%) MODERATE 1.05) fewer to 48 more) 1 randomise not not serious not serious not serious none 40/40 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Marginal adaptation s ) ) 1.05) (from 40 fewer to 20 fewer 50 more) RR 0.98 per 1000 randomised serious 87/89 97/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.91 to (from 90 CRITICAL trials (97.8%) (100.0%) Comparison of self-etch and total-etch strategy at 36th month under FDI - Marginal adaptation MODERATE 1.06) fewer to 60 more) 1 randomise not not serious not serious not serious none 40/40 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH Comparison of self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Absence of secondary caries s ) ) 1.05) (from 40 fewer to 0 fewer 50 more) RR 1.00 per 1000 randomised serious 89/89 97/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.97 to (from 30 CRITICAL trials (100.0%) (100.0%) MODERATE Comparison of self-etch and total-etch strategy at 36th month under FDI - Absence of secondary caries 1.03) fewer to 30 more) 1 randomise not not serious not serious not serious none 40/40 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH Comparison self-etch and total-etch adhesive strategy at 24th month under FDI criteria - Absence of post-operative sensitivity s ) ) 1.05) (from 40 10 more fewer to RR 1.01 per 1000 50 more) randomised serious 88/88 96/97 ⨁⨁⨁◯ 2 not serious not serious not serious none (0.97 to (from 30 IMPORTANT trials c (100.0%) (99.0%) 1.05) fewer to MODERATE Comparison of self-etch and total-etch strategy at 36th month under FDI - Absence of post-operative sensitivity 49 more) 1 randomise not not serious not serious not serious none 42/42 44/44 RR 1.00 0 fewer ⨁⨁⨁⨁ CRITICAL Comparison self-etch and total-etch adhesive strategy at 24th month under FDI criteria - total d trials seriou (100.0% (100.0% (0.96 to per 1000 HIGH s ) ) 1.05) (from 40 0 fewer fewer to RR 1.00 per 1000 randomised serious 436/449 481/491 ⨁⨁⨁◯ 50 more) 10 not serious not serious not serious none (0.98 to (from 20 CRITICAL trials c (97.1%) (98.0%) 1.02) fewer to MODERATE Comparison of self-etch and total-etch strategy at 36th month under FDI - total 20 more) 5 randomise not not serious not serious not serious none 202/207 220/221 RR 0.98 20 fewer ⨁⨁⨁⨁ CRITICAL d trials seriou (97.6%) (99.5%) (0.95 to per 1000 HIGH s 1.01) (from 50 fewer to 10 more) various adhesive strategies of universal adhesives concluded that there was no signiﬁcant difference between the total-etch and self etch strategy, although it slightly favoured the total-etch strategy in terms of retention, absence of fracture and secondary caries. The major difference between universal adhesives and tradi- Although our results obtained no signiﬁcant difference tional one-step SE adhesives is the presence of functional between the two adhesive strategies employed, it is worthwhile phosphate and/or carboxylate monomers in universal adhesives, to know that the certainty of evidence fell from high certainty (in for example 10-MDP (10-methacryloyloxydecyl dihydrogen phos- the 18th month followup under the FDI criteria) to moderate-low phate), GPDM (glycerol-phosphate dimethacrylate), PENTA (dipen- taerythritol penta acrylate monophosphate), PAC (polyalkenoic certainty in the 24 and 36 month follow-ups. There was a acid copolymer), etc. The high-quality bonding performance can difference seen in the certainty of evidence among the two be explained by the presence of the functional monomer 10-MDP criteria as well. This may be because the number of studies in most Universal adhesives. 10-MDP includes a methacrylate varied at each follow-up as well as in each evaluation criteria. polymerizable end, a long hydrophobic 10-carbon chain and a Different studies were evaluated under each criteria at every short hydrophilic phos[hate component that is capable of ionizing follow-up period. The certainty of evidence was high for the and interacting with hydroxyapatite. Apart from the ability of nano 36 month followup under the FDI criteria, but only one study layering, the presence of the long carbon chain in this molecule was included in this meta-analysis. Hence results of the longer has also been reported to contribute to the excellent bonding follow-ups must be interpreted with caution. The sensitivity ability of universal adhesives [51]. The longer chains make the analysis done after eliminating the high risk studies concluded monomer more hydrophobic, which may enhance the chemical that no signiﬁcant difference was obtained, and hence the interaction with calcium and reduce their degradation [52]. results of the meta-analysis could be considered in spite of including studies with high risk of bias (Tables 3–6). The major strength of our systematic review is that we have The funnel plot analysis revealed that there was a strong risk of evaluated the clinical performance of Universal adhesives in publication bias in the retention domain at the 18th month follow- NCCLs separately at various follow-up periods. The follow-up up under FDI criteria suggesting that the results must be period has an impact on the clinical performance of restorations interpreted with caution and cannot be generalised to a larger and hence an appropriate analysis must evaluate data from population. various studies at the same follow-up period. Another strength is BDJ Open (2023) 9:6 K. Doshi et al. that our meta-analysis evaluates data using different evaluation 14. Erhardt MCG, Cavalcante LMA, Pimenta LAF. Inﬂuence of phosphoric acid pre- treatment on self-etching bond strengths [Internet]. J Esthet Restor Dent. criteria (USPHS and FDI), separately, since both these criteria have 2004;16:33–40. Available from: https://doi.org/10.1111/j.1708- different speciﬁcations. Additionally, we used the most recently 8240.2004.tb00448.x. introduced and highly speciﬁc Cochrane’s RoB2 tool for quality 15. Rotta M, Bresciani P, Moura SK, Grande RHM, Hilgert LA, Baratieri LN, et al. Effects assessment, which was introduced in 2019. The previous version of phosphoric acid pretreatment and substitution of bonding resin on bonding had some issues with assessment of bias due to incomplete effectiveness of self-etching systems to enamel. J Adhes Dent. 2007;9:537–45. outcome data and selective reporting of outcomes causing 16. Alex G. Universal adhesives: the next evolution in adhesive dentistry? Compend particular difﬁculties, and confusion over whether studies that Contin Educ Dent. 2015;36:15–26. were not blinded should automatically be considered to be at 17. Perdigão J, Kose C, Mena-Serrano AP, De Paula EA, Tay LY, Reis A, et al. A new high risk of bias. RoB2 takes into account the risk of bias in the universal simpliﬁed adhesive: 18-month clinical evaluation [Internet]. Operative meta-analyses and review conclusions as well. Hence, it is a more Dent. 2014;39:113–27. https://doi.org/10.2341/13-045-c. 18. Hanabusa M, Mine A, Kuboki T, Momoi Y, Van Ende A, Van Meerbeek B, et al. rigorous assessment of the quality of the clinical trial. Bonding effectiveness of a new “multi-mode” adhesive to enamel and dentine. J. A major limitation of our review is the low and moderate Dent. 2012;40:475–84. certainty of evidence observed at these short and medium-term 19. Muñoz MA, Luque-Martinez I, Malaquias P, Hass V, Reis A, Campanha NH, et al. In follow-ups, the literature suggests that it may take more than 5 vitro longevity of bonding properties of universal adhesives to dentin. Oper Dent. years to observe a signiﬁcant number of events between the 2015;40:282–92. treatment groups in clinical settings [53]. Unfortunately, we could 20. Muñoz MA, Luque I, Hass V, Reis A, Loguercio AD, Bombarda NHC. Immediate not run a meta-analysis for long-term follow-ups since only one bonding properties of universal adhesives to dentine. J. Dent. 2013;41:404–11. study [27] evaluated the NCCL restorations after 5 years of clinical 21. Szesz A, Parreiras S, Reis A, Loguercio A. Selective enamel etching in cervical lesions for self-etch adhesives: A systematic review and meta-analysis. J Dent. function, and found superior clinical performance for total etch 2016;53:1–11. and selective etch compared to self etch strategy. 22. 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Follow-up of ﬂowable resin AUTHOR CONTRIBUTIONS composites performed with a universal adhesive system in non-carious cervical KD: conceptualisation, methodology, literature search, data extraction, writing of lesions: A randomized, controlled 24-month clinical trial. Am J Dent. original draft. NMS: conceptualization, methodology, reviewing and editing draft, 2020;33:39–42. supervision, project administration. AB: Statistics and meta-analysis. PS: Literature 39. Ruschel VC, Stolf SC, Shibata S, Chung Y, Boushell LW, Baratieri LN, et al. Three- search, Data extraction, validation, supervision, project administration. DPAS: year clinical evaluation of universal adhesives in non-carious cervical lesions. Am. Reviewing and editing the draft, supervision, project administration. BJ: Reviewing J. Dent. 2019;32:223–8. and editing draft. RS: Reviewing and editing draft. 40. Cruz J, Silva A, Eira R, Coito C, Lopes M, Faculdade de Medicina Dentária da Universidade de Lisboa, Lisbon, Portugal, et al. 6-month clinical performance of a universal adhesive on non-carious cervical lesions: self-etch and etch- COMPETING INTERESTS and-rinse techniques. Rev Port Estomatol Med Dent Cir Maxilofac [Internet]. The authors declare no competing interests. 2020 14;61. Available from: http://revista.spemd.pt/article/1544. 41. Perdigão J, Ceballos L, Giráldez I, Baracco B, Fuentes MV. Effect of a hydrophobic ETHICS APPROVAL bonding resin on the 36-month performance of a universal adhesive—a ran- Our Institutional Human Ethics Committee abides in accordance with the National domized clinical trial. Clin Oral Investig. 2020;24:765–76. Statement on Ethical Conduct in Human Research (2007 updated in 2018). The 42. de Paula EA, Tay LY, Kose C, Mena-Serrano A, Reis A, Perdigão J, et al. Rando- National Statement on Ethical Conduct in Human Research allows certain human mized clinical trial of four adhesion strategies in cervical lesions: 12-month research to be exempted from ethical review, it is a negligible risk research and results. Int J Esthet Dent. 2015;10:122–45. involves only the use of existing collections of data or records that contain only non- 43. Hickel R, Peschke A, Tyas M, Mjör I, Bayne S, Peters M, et al. FDI World Dental identiﬁable data about human beings (Section 5.1.22-23). Federation: clinical criteria for the evaluation of direct and indirect restorations— update and clinical examples. Clin Oral Investig. 2010;14:349–66. 44. Van Meerbeek B, Yoshihara K, Yoshida Y, Mine A, De Munck J, Van, et al. State of ADDITIONAL INFORMATION the art of self-etch adhesives. Dent Mater. 2011;27:17–28. 45. Hashimoto M, Tay FR, Svizero NR, de Gee AJ, Feilzer AJ, Sano H, et al. The effects Supplementary information The online version contains supplementary material of common errors on sealing ability of total-etch adhesives. Dent Mater. available at https://doi.org/10.1038/s41405-022-00124-6. 2006;22:560–8. 46. Yoshihara K, Hayakawa S, Nagaoka N, Okihara T, Yoshida Y, Van Meerbeek B. Correspondence and requests for materials should be addressed to Riluwan Etching efﬁcacy of self-etching functional monomers. J. Dent. Res. 2018;97:1010–6. Siddique. 47. Fukegawa D, Hayakawa S, Yoshida Y, Suzuki K, Osaka A, Van, et al. Chemical interaction of phosphoric acid ester with hydroxyapatite. J Dent Res. 2006;85:941–4. Reprints and permission information is available at http://www.nature.com/ 48. Yoshihara K, Yoshida Y, Nagaoka N, Fukegawa D, Hayakawa S, Mine A, et al. Nano- reprints controlled molecular interaction at adhesive interfaces for hard tissue recon- struction. Acta Biomater. 2010;6:3573–82. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims 49. Josic U, Maravic T, Mazzitelli C, Radovic I, Jacimovic J, Del Bianco F, et al. Is clinical in published maps and institutional afﬁliations. behavior of composite restorations placed in non-carious cervical lesions inﬂu- enced by the application mode of universal adhesives? A systematic review and meta-analysis. Dent Mater [Internet]. 20211; Available from: https://doi.org/ 10.1016/j.dental.2021.08.017. 50. Arbildo-Vega H, Lamas-Lara C, Cruzado-Oliva F, Rosas-Prado C, Gómez-Fuertes A, Open Access This article is licensed under a Creative Commons Vásquez-Rodrigo H. Comparison of the clinical effect of the adhesive strategies of Attribution 4.0 International License, which permits use, sharing, universal adhesives in the treatment of non-carious cervical lesions. Systematic adaptation, distribution and reproduction in any medium or format, as long as you give review and meta-analysis. Int J Oral Biol. 2018;7:210–22. appropriate credit to the original author(s) and the source, provide a link to the Creative 51. Yoshihara K, Yoshida Y, Nagaoka N, Hayakawa S, Okihara T, De Munck J, et al. Commons license, and indicate if changes were made. The images or other third party Adhesive interfacial interaction affected by different carbon-chain monomers. material in this article are included in the article’s Creative Commons license, unless Dent Mater. 2013;29:888–97. indicated otherwise in a credit line to the material. If material is not included in the 52. Feitosa VP, Sauro S, Ogliari FA, Ogliari AO, Yoshihara K, Zanchi CH, et al. Impact of article’s Creative Commons license and your intended use is not permitted by statutory hydrophilicity and length of spacer chains on the bonding of functional mono- regulation or exceeds the permitted use, you will need to obtain permission directly mers. Dent Mater. 2014;30:e317–23. from the copyright holder. To view a copy of this license, visit http:// 53. Pannuti CM, Sendyk DI, Graças YT das, Takai SL, de Paulo Aragão SABÓIA V, creativecommons.org/licenses/by/4.0/. Romito GA, et al. Clinically relevant outcomes in dental clinical trials: challenges and proposals [Internet]. Vol. 34, Brazilian Oral Research. 2020. Available from: https://doi.org/10.1590/1807-3107bor-2020.vol34.0073. © The Author(s) 2023 BDJ Open (2023) 9:6

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References

Clinical status of dentine bonding agents

Douglas, WH
Alternations in the staining reaction of dentine resulting from a constituent of a new self-polymerizing resin

Kramer, IRH
Hybrid layer as a dentin-bonding mechanism

Nakabayashi, N; Nakamura, M; Yasuda, N
A simple method of increasing the adhesion of acrylic filling materials to enamel surfaces

Buonocore, MG
An overview of dentin bonding agents

Kadali, NS; Alla, RK; Guduri, V; Mc, SS
Total-etch versus self-etch adhesive: Effect on postoperative sensitivity

Perdigão, J; Geraldeli, S; Hodges, JS
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Featherstone, RW
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Lawson, NC; Robles, A; Fu, CC; Lin, CP; Sawlani, K; Burgess, JO
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Soetojo, A
Microtensile bond strength of a total-etch 3-step, total-etch 2-step, self-etch 2-step, and a self-etch 1-step dentin bonding system through 15-month water storage

Armstrong, SR; Vargas, MA; Fang, Q; Laffoon, JE
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Pashley, DH; Tay, FR; Breschi, L; Tjäderhane, L; Carvalho, RM; Carrilho, M
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Peumans, M; De Munck, J; Mine, A; Van Meerbeek, B
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Tay, FR; Pashley, DH
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Lopes, LS; Calazans, FS; Hidalgo, R; Buitrago, LL; Gutierrez, F; Reis, A
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de Albuquerque, EG; Warol, F; Calazans, FS; Poubel, LA; Marins, SS; Matos, T
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Atalay, C; Ozgunaltay, G; Yazici, AR
Multi-Mode adhesives performance and success/retention rates in NCCLs restorations: randomised clinical trial one-year report

Manarte-Monteiro, P; Domingues, J; Teixeira, L; Gavinha, S; Manso, MC
Effect of dentin roughness on the adhesive performance in non-carious cervical lesions: A double-blind randomized clinical trial

Loguercio, AD; Luque-Martinez, IV; Fuentes, S; Reis, A; Muñoz, MA
OCT for early quality evaluation of tooth–composite bond in clinical trials

Haak, R; Schmidt, P; Park, KJ; Häfer, M; Krause, F; Ziebolz, D
18-month clinical evaluation of a copper-containing universal adhesive in non-carious cervical lesions: A double-blind, randomized controlled trial

Matos, TP; Gutiérrez, MF; Hanzen, TA; Malaquias, P; de Paula, AM; de Souza, JJ
Bonding performance of simplified adhesive systems in noncarious cervical lesions at 2-year follow-up: a double-blind randomized clinical trial

Zanatta, RF; Silva, TM; Esper, M; Bresciani, E; Gonçalves, S; Caneppele, T
The effect of diode laser application on restoration of non carious cervical lesion: Clinical follow up

Akarsu, S; Karademir, SA; Ertas, E; Atasoy, S
Catechin-based dentin pretreatment and the clinical performance of a universal adhesive: a two-year randomized clinical trial

Costa, C; Albuquerque, N; Mendonça, JS; Loguercio, AD; Saboia, V; Santiago, SL
Follow-up of flowable resin composites performed with a universal adhesive system in non-carious cervical lesions: A randomized, controlled 24-month clinical trial

Kemaloğlu, H; Atalayin Ozkaya, C; Ergucu, Z; Onal, B
Three-year clinical evaluation of universal adhesives in non-carious cervical lesions

Ruschel, VC; Stolf, SC; Shibata, S; Chung, Y; Boushell, LW; Baratieri, LN
Effect of a hydrophobic bonding resin on the 36-month performance of a universal adhesive—a randomized clinical trial

Perdigão, J; Ceballos, L; Giráldez, I; Baracco, B; Fuentes, MV
Randomized clinical trial of four adhesion strategies in cervical lesions: 12-month results

de Paula, EA; Tay, LY; Kose, C; Mena-Serrano, A; Reis, A; Perdigão, J
FDI World Dental Federation: clinical criteria for the evaluation of direct and indirect restorations—update and clinical examples

Hickel, R; Peschke, A; Tyas, M; Mjör, I; Bayne, S; Peters, M
State of the art of self-etch adhesives

Van Meerbeek, B; Yoshihara, K; Yoshida, Y; Mine, A; De Munck, J; Van
The effects of common errors on sealing ability of total-etch adhesives

Hashimoto, M; Tay, FR; Svizero, NR; de Gee, AJ; Feilzer, AJ; Sano, H
Etching efficacy of self-etching functional monomers

Yoshihara, K; Hayakawa, S; Nagaoka, N; Okihara, T; Yoshida, Y; Van Meerbeek, B
Chemical interaction of phosphoric acid ester with hydroxyapatite

Fukegawa, D; Hayakawa, S; Yoshida, Y; Suzuki, K; Osaka, A; Van
Nano-controlled molecular interaction at adhesive interfaces for hard tissue reconstruction

Yoshihara, K; Yoshida, Y; Nagaoka, N; Fukegawa, D; Hayakawa, S; Mine, A
Comparison of the clinical effect of the adhesive strategies of universal adhesives in the treatment of non-carious cervical lesions. Systematic review and meta-analysis

Arbildo-Vega, H; Lamas-Lara, C; Cruzado-Oliva, F; Rosas-Prado, C; Gómez-Fuertes, A; Vásquez-Rodrigo, H
Adhesive interfacial interaction affected by different carbon-chain monomers

Yoshihara, K; Yoshida, Y; Nagaoka, N; Hayakawa, S; Okihara, T; De Munck, J
Impact of hydrophilicity and length of spacer chains on the bonding of functional monomers

Feitosa, VP; Sauro, S; Ogliari, FA; Ogliari, AO; Yoshihara, K; Zanchi, CH

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Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis

Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis

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Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis

Effect of adhesive strategy of universal adhesives in noncarious cervical lesions – an updated systematic review and meta-analysis

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