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Corresponding author: Dr Maria João Calheiros-Lobo, UNIPRO - Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS - CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra PRD, PORTUGAL
Clinical Professor, Department of Conservative Dentistry and Researcher, UNIPRO - Oral Pathology and Rehabilitation Research Unit, IUCS - CESPU, Gandra, Portugal
Computer-aided design and computer-aided manufacturing (CAD-CAM) blocks have evolved rapidly, making it difficult to establish the best clinical protocol for bonding a given block and whether an established protocol is appropriate for a newly introduced product.
Purpose
This integrative systematic review and meta-analysis aimed to clarify whether the clinician can select the most efficient adhesion protocols for CAD-CAM blocks by reading published in vitro studies and implementing them in daily practice.
Material and methods
Based on the population, intervention, comparison, and outcome (PICO) strategy, 3 databases were searched for in vitro studies, randomized clinical trials, prospective or retrospective studies, and case reports from January 1, 2015, to July 31, 2021. A meta-analysis analyzed 28 studies to calculate the mean difference between best and worst protocols for each author and block with a random-effects model (α=.05).
Results
From 508 relevant studies, 37 in vitro studies, 2 clinical studies, and 1 clinical report were selected for data extraction and qualitative analysis. Vita Enamic, IPS e.max CAD, LAVA Ultimate, and Vita Mark II blocks were the most studied, and RelyX Ultimate was the most used luting cement. The meta-analysis confirmed the null hypothesis that the evidence-based efficacy of clinical protocols to bond CAD-CAM blocks is still controversial (P<.05).
Conclusions
There are objective standards for individual in vitro tests, but the studies lack standardization. Some tested protocols were more efficient than others. Randomized clinical trials and well-documented clinical situations were almost nonexistent, making direct application of in vitro findings in clinical practice impossible.
Clinical Implications
Clinicians must conscientiously update adhesive protocols and techniques for each new material based on the manufacturer’s instructions. Technical requirements may differ for similar products within the same brand and even for products with similar names from other brands.
Computer-aided design and computer-aided manufacturing (CAD-CAM) is becoming common in restorative dentistry, facilitating the manufacturing and delivery of indirect esthetic restorations.
Review on polymer, ceramic and composite materials for CAD/CAM indirect restorations in Dentistry - Application, mechanical characteristics and comparison.
Review on polymer, ceramic and composite materials for CAD/CAM indirect restorations in Dentistry - Application, mechanical characteristics and comparison.
The quality, bond strength, and clinical longevity of CAD-CAM restorations appear to have increased, with contemporary restorations having excellent performance.
Composite resins have more straightforward fabrication and favorable properties, with lower hardness, lower elastic modulus, and straightforward cementation.
Bonding is essential for CAD-CAM indirect restorations, both ceramic and composite resin, as they rely on adhesion for retention and strength, both of which directly affect their longevity.
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Recent advances in chemical modification of the composite resin cement with, for example, the introduction of antibacterial agents and multifunctional monomers improved the adhesive bond strength to dentin, enhancing long-term performance and protecting the tooth-adhesive interface from microleakage.
The optimal surface treatment for interface substrates and the best luting cement, restoration material, and dentin bonding agent to produce the highest bond strength is unclear. A consensus regarding the optimal adhesive protocol is lacking.
Composite resin cement has been used for its advantageous mechanical and adhesive properties to cement conventional metal crowns, fixed partial dentures, ceramic crowns, veneers, or to repair fractured metal-ceramic, ceramic, and composite resin restorative materials.
The composition of CAD-CAM blocks influences the bond strength of the ceramic material, and the mechanical and chemical interactions between the substrate and the bonding agent.
A combination of mechanical and chemical strategies has been the most accepted procedure for enhancing the composite resin cement-to-glass–ceramic bonding.
Silane provides chemical adhesion to silica-containing ceramic substrates. In addition, acid etchants, such as hydrofluoric acid, can partially dissolve the glassy phase, improving mechanical interlock with the composite resin cement.
For clinicians, selecting the ideal surface treatment protocol or adequate luting agent for each material is a significant concern as they are aware of its influence on the long-term success of the restoration.
This integrative systematic review and meta-analysis aimed to determine whether a clinician can select the most efficient adhesion protocol for each CAD-CAM block by reading published in vitro studies and implementing them in daily practice. In addition, the in vitro adhesion of CAD-CAM blocks reported in the literature was compared with the in vivo efficacy of the protocols. The research hypotheses were that the clinical protocols for CAD-CAD block adhesion would be well established and clinically reproducible or that the evidence-based efficacy of clinical protocols to adhere CAD-CAM blocks would remain controversial.
Material and methods
The review followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020 recommendations.
The population, intervention, comparison, and outcome (PICO) question was as follows: “Do in vitro findings influence the clinical protocols for the adhesion of CAD-CAM blocks?” The CAD-CAM blocks constituted the population. The intervention was defined as the adhesion protocol performed on the block or teeth for cementation; specifically, teeth or block surface treatment, type of block, coupling agent, and luting cement. The comparison was made between protocols for each CAD-CAM block to find intrastudy and interstudy differences in the mechanical performance. Clinical protocols were the outcome.
A bibliographic search was carried out in the databases Medline/PubMed, ScienceDirect, and EBSCOhost, with keywords combined in the Boolean expression: [(CAD-CAM) AND (adhesive OR adhesion OR bonding OR cement) AND (ceramics OR blocks) AND protocol], filtered by the English language. Inclusion criteria were research papers, randomized clinical trials (RCTs), and clinical cases that addressed the theme, published from January 1, 2015 to July 31, 2021, with accessible full text. Duplicates and papers published before 2015 were excluded.
Retrieved pertinent systematic reviews and reviews were not included in the qualitative analysis, but were still included in the study. Also included were those found by manual search, done by pairing each key word with the word CAD or by searching the reference lists of the included articles to allow comparisons, and broadening of the introduction and discussion sections. Duplicate articles were preliminarily withdrawn with a citation manager (EndNote X8 Windows; Clarivate). Articles were then filtered by title, abstract, and complete reading, agreeing with the PRISMA Statement, as shown in Figure 1. Two investigators (M.J.C.L., R.C.) independently selected each pertinent article for detailed reading. A third investigator (T.P.) resolved disagreements.
Figure 1Flow diagram of study selection according to preferred reporting items for systematic reviews and meta-analysis statement.
Qualitative analysis for risk of bias assessment was done by individually scoring the 10 elected parameters within the following criteria: (0) clearly mentioned, (1) present but not accurately mentioned, and (2) not mentioned. Global scoring was categorized as Low Risk (0-4), Medium Risk (5-12), High Risk (13-17), and Very High Risk (18-20) of bias. The SJR score (Q1-Q4) was assigned by publication date for each study. The quality assessment of the observational studies was done by an adapted grading of recommendations, assessment, development, and evaluations (GRADE) method.
Data extraction was summarized in tables. Pertinent information was examined in comprehensive graphics after applying the following filters: type of CAD-CAM block tested, luting material used in the laboratory and in vivo tests, mechanical test used for bonding strength evaluation, light source intensity, type of surface treatment, and coupling agent.
A meta-analysis focused on adhesive strategies for each type of CAD-CAM block was conducted using a software program (Stata v17.0; StataCorp). Subgroup analyses were performed to assess the different kinds of surface treatment methods, adhesive joint substrates, and types of mechanical tests, and, for all studies that evaluated more than 1 type of CAD-CAM block or more than 1 surface treatment method, each type of material or treatment method was considered independently.
The statistical heterogeneity was detected using the I2 statistic test (α=.05). A subgroup was formed with the 28 articles that studied the 9 most tested blocks in at least 2 in vitro studies. A meta-analysis was conducted by the authors and CAD-CAM block to find intrastudy heterogeneity and protocol splitting by efficiency after calculating the difference between means and the effect size (α=.05; 95% CI; Z-value=1.96). Funnel and Galbraith plots assessed the publication bias and heterogeneity (random-effects model; α=.01; 99.9% CI; Z-value=2.58).
Results
The search retrieved 508 articles (Medline/PubMed [108], ScienceDirect [176], EBSCOhost [224]). After applying inclusion and exclusion criteria, 37 in vitro studies,
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
Review on polymer, ceramic and composite materials for CAD/CAM indirect restorations in Dentistry - Application, mechanical characteristics and comparison.
(2.7%) and 36 medium-risk of bias (97.3%) articles. Transversal factors for lower score were the absence of operator blindness (referred to in 1 article
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
[13.5%]). Specimen randomization and the control group were frequently inadequately described or lacking. The level of evidence of the 2 observational studies is shown in Table 2. Given the parameters, the non-RCTs were scored as very good
achieved good quality (within the scientific knowledge and manufacturer’s instructions despite not using a dental dam, and given the periodontal health, supragingival margins, and a cooperative patient).
Table 1Synthesis of qualitative analysis for risk of bias assessment
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
NS, Not scored; Q1, First quartile; Q2, Second quartile; Q3, Thrid quartile; ( ) - Quartile in the previous year. Green- good score/low risk, orange- average score/medium risk, red- bad score/high risk.
Table 2Methodological evaluation of studies according to grading of recommendations, assessment, development, and evaluations method (adapted scale of 0-20)
Items
Criteria
Application
Risk of bias
Randomized or observational
[-1] J-risk of serious bias [-2] • very serious
Inconsistency of results (heterogeneity)
Assessment of similarities and estimates
[-1] important inconsistency
Indirect evidence
Evaluation of the presence of differences in the population, intervention and outcomes between the Included studies and the review question
[-1] - serious indirect evidence [-2] - very serious
Imprecision
Sample dimension
[•1] ifn<50, [-2] ifn<30
Publication/methodology bias
Lack of methodological information
[-1] suspicion of publication bias or lack of information
Weighting for observational studies
Impact of the Journal
Evaluation of the impact of the journal
Maximum impact (Q1) - [+2]
Variation in relation to the average of studies in the held work
Evaluation of variation of the Identical studies
On average of identical studies •1+2]
Effectiveness of the treatment
Evaluation of effectiveness
Good clinical performance [+2]
Sample size
Evaluation of the sampled size of the study
If >50 - [+2J]: if >30 - [+1]
Well-founded study
Assessment of the rationale of the article
Well-founded [+2]
Archibald et al, 2017
Spitznagel et al, 2018
Bias risk (randomized or observational)
3
3
Inconsistency of results (heterogeneity)
-
-
Indirect evidence
-
-
Imprecision
-
-
Methodology
2
2
Weighting for observational studies
Journal Impact (+2ifQ1)
2
2
Effect with % within the range of other studies in the field (42)
Data extraction from in vitro and in vivo studies is shown in Table 3, Table 4, Table 5, Table 6. The authors identified 686 protocols to adhere 37 different CAD-CAM blocks (Supplementary Table 1 available online). Filtered data are displayed in Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7. The meta-analysis with the initial 37 selected in vitro studies, combining various agents of the adhesive strategy, revealed very high heterogeneity (I2>99%) in all attempts, even with a random-effects model (α=.05), and gave illegible graphics because of the large number of entries; therefore, results are not displayed. The meta-analysis based on the difference between means and effect size (P=.05; 95% CI; Z-value=1.9599) (Supplementary Table 2 available online) conducted by data filtering is shown in the forest plots (Fig. 8 and 9). Overall, tested protocols performed better than control protocols, but differences were evident. The IPS e.max ZirCAD bonding to substrates was not consistent in various studies with the need for simultaneous physico-chemical treatment of the block surface, and immediate dentin sealing (IDS) with a universal self-adhesive followed by a low-viscosity resin-matrix restorative favored adhesion to the tooth. As a second joint substrate, only composite resin bonded to IPS e.max ZirCAD raised concerns.
Table 3Resumed data extraction from the selected in vitro studies
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
Restoration assessment - modified United States Public Health Service (USPHS) criteria Two independent investigators Dropouts - 42% Participants not coming into the clinic – via telephone or email
Figure 4Number of studies using each type of test. μSBS, microshear bond strength; μTBS, microtensile bond strength; SBS, shear bond strength; TBS, tensile bond strength.
Figure 8Forest plot summarizing effect size between control protocols and all other tested protocols by CAD-CAM block, luting cement, and tooth surface treatment. CAD-CAM, computer-aided design and computer-aided manufacturing.
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
based on the difference between means and the effect size (P=.05; 95% CI; Z-value=1.9599) is represented in Figure 10. For the most tested blocks, best and worst adhesion protocols were identified (Table 7). Supplementary Tables 3 and 4 (available online) show more and less favorable protocols. Figure 11 shows the highest and lowest mean results obtained according to the test and joint substrate. Assessment of publication bias and heterogeneity is shown in Figures 12 and 13. The funnel plot asymmetry suggests an overestimation of the intervention effect, probably induced by the disparity between samples, with some possible bias. Studies that tested composite resin or luting cement as the second joint substrate and those that used microshear bond strength (μSBS) or microtensile bond strength (μTBS) tests had more publication bias. The Galbraith plot suggests an absence of substantial heterogeneity among the effect size (only 2 studies outside the 99.9% CI region). All studies had high precision (toward the right on the X-axis). Globally the studies were above the green line with the red line sloping upward, suggesting favorable tested protocols compared with the control protocol.
Figure 10Forest plot summarizing effect size by joint substrate, mechanical test, and bonding protocol by study and most tested blocks.
Al2O3, aluminum oxide; HF, hydrofluoric acid; il, inferior limit; ul - upper limit; NO, not used; SD, standard deviation; SiC, silica paper abrasive; μSBS, micro-shear bond strength; SBS, shear bond strength; μTBS, micro-tensile bond strength; TBS, tensile bond strength.
Figure 11Means by kind of test and substrate for mainly used blocks. μSBS, microshear bond strength; μTBS, microtensile bond strength; SBS, shear bond strength; TBS, tensile bond strength.
This review accessed whether in vitro findings concerning the strength of the bonding between CAD-CAM blocks and different substrates could be easily perceived by clinicians and incorporated into the daily clinical protocols, and was developed to integrate laboratory and clinical studies. Limiting the search to publications from the last 7 years restricted the review to materials used in contemporary clinical practice. Bias should not have occurred since, in the last 20 years, 70% of the articles were from that period. Based on the existing data (P<.05), the hypothesis that evidence-based efficacy for clinical protocols to adhere the different CAD-CAD blocks is still controversial, was accepted.
Given the descriptive results (Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7), meta-analyses for each material subgroup were conducted. Still, as the technical protocol (specific sequence of technical steps) was the focus of this review, that methodology was abandoned, as the study would lose interest. Furthermore, as what should be chosen to be combined in a meta-analysis can be subjective and does not always fit into statistical solutions, after discussion, clinical judgment, and judicious consensus, a new meta-analysis focused on the best and worst adhesion protocols for each CAD-CAM block was carried out.
The tested protocols identified (N=686), reflected the search for solutions to deliver long-lasting functional and esthetic restorative treatments dependent on a stable union between the restorative material and the dentin,
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
However, the lack of systematization and standardization makes it difficult for clinicians to identify an evidence-based process that is easily reproducible in daily practice, as stated during the data extraction process (Table 3, Table 4, Table 5). Despite that, there was agreement among authors on the importance of using appropriate luting cement, surface conditioners, and bonding agents to obtain durable restorations.
of German dentists showed the frequent use of inappropriate bonding methods, drawing attention to the benefit of establishing straightforward bonding protocols with clear evidence-based criteria.
A medium score of risk of bias in most articles is the probable cause of some bias confirmed by the funnel plots (Fig. 12). Globally, the articles were well structured. The 2 articles
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
were excluded from the meta-analyses since the reported results did not allow a rigorous reading or statistical treatment.
Matching in vitro with in vivo studies had evident limitations. Of the 2 in vivo observational studies, 1 used pressed ceramic IPS e.max and IPS e.max CAD,
at 3.5 and 3 years, respectively). The materials in these studies matched the most tested blocks of the 37 in vitro studies. RelyX Ultimate, Variolink Esthetic, and Variolink II were the luting materials used, corroborating the trend of choice either for in vitro or in vivo studies.
Among the most in vitro tested blocks, IPS e.max CAD (lithium disilicate) >Vita Enamic (hybrid ceramic with a dual ceramic-polymer network structure) =LAVA Ultimate (80% nanoceramic resin) >Vita Mark II (reinforced nanoleucite crystals feldspathic porcelain), none require high-temperature crystallization, with no need for laboratory processing and facilitating in-office handling. Some tested in vitro protocols exposed dental laboratory technicians, clinicians, or patients to risk (high temperature, acids, or both), despite inducing the best mechanical performance for a specific material.
as did the protocols simulating aging or bonding failure. The choice of the best CAD-CAM block-adhesive system pair for clinical use was complex, as referred to in 1 article.
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
No temporal association was found between the type of test and year of publication, neither with the material tested nor the paired adhered materials. Tests with human teeth showed a lower difference between the means (Fig. 11) with the worst adhesive performances. The highest absolute values were more dependent on the paired joint substrates and tested protocols than on the test performed.
Protocols simulating aging or material fatigue differed among studies concerning thermocycling, ranging from 5000
cycles, with different moisture and temperature conditions for the same test. Specimens were kept in water, not reproducing the dynamic oral environment (temperature, saliva baths, occlusal loads, or eventual parafunctional habits).
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
Storage in nonspecified water, deionized water, distilled water, or saline solution was identified. Initial storage was usually 24 hours, except in 4 studies (30 minutes,
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
A convergence for the objective temperature (37 oC) was found. Wavelengths in light-polymerizing protocols were 650 to 1560 mW/cm2 (1200 mW/cm2 in approx. 67.5% of the studies), and polymerization times were 20 seconds
The number of available materials makes it impossible to test all of them at the same time, forcing researchers to restrict testing, a limitation because, even though a dual-polymerizing composite resin cement is the standard for adhesive cementation, different brands have different properties and components.
These differences were the main reason for subgrouping the cements and CAD-CAM blocks by the authors. Researchers select some materials over others, reflecting the choice for more user-friendly materials. The most tested luting cement was Rely X Ultimate,
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
probably because it combines dual polymerization with the possibility of total-etch, selective-etch, or self-etch adhesive strategies. However, the chosen materials may have been conditioned by research support from the manufacturer or by the clinical preference of the researcher.
Conclusions
Based on the findings of this systematic integrative review and meta-analysis, the following conclusions were drawn:
1.
Despite the objective standards for the individual in vitro tests, a lack of standardization for each technical step was evident.
2.
Some tested protocols were more efficient than others for each CAD-CAM block.
3.
The number of protocols found makes selecting the most suitable protocol for each block or clinical situation difficult for the clinician.
4.
Randomized clinical trials were nonexistent, and well-documented clinical situations were scarce, making the inference of direct application of in vitro findings into clinical practice impossible.
5.
Based on the data collected, a rapid and efficient translation from in vitro scientific evidence to clinical practice is a complex and time-consuming task.
CRediT authorship contribution statement
Maria João Calheiros-Lobo: Conceptualization, Methodology, Investigation, Software, Formal analysis, Writing – original draft. Ricardo Carbas: Formal analysis, Investigation, Visualization, Writing – review & editing. Lucas F.M. da Silva: Supervision, Validation, Writing – review & editing. Teresa Pinho: Investigation, Formal analysis, Writing – review & editing, Supervision, Project administration.
Acknowledgments
The authors thank, Dr Denis Lopes, from the Dental Medicine Department, University Institute of Health Sciences, IUCS - CESPU, Gandra, Portugal, as a participating investigator for his contribution to collecting and organizing the data.
Review on polymer, ceramic and composite materials for CAD/CAM indirect restorations in Dentistry - Application, mechanical characteristics and comparison.
Effect of MDP-containing silane and adhesive used alone or in combination on the long-term bond strength and chemical interaction with lithium disilicate ceramics.
Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: an in vitro study.
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