Misfit of Implant-Supported Zirconia (Y-TZP) CAD-CAM Framework Compared to Non-Zirconia Frameworks: A Systematic Review

Objective: The aim of the study was to systematically review the overall outcomes of studies comparing the misfit of yttria-stabilized zirconia (Y-TZP) CAD-CAM implant-supported frameworks with frameworks fabricated with other materials and techniques. Methods: An electronic literature search of English literature was performed using Google Scholar, Scopus, Web of Science, MEDLINE (OVID), EMBASE, and PubMed, using predetermined inclusion criteria. Specific terms were utilized in conducting a search from the inception of the respective database up to May 2022. After the search strategy was applied, the data were extracted and the results were analyzed. The focused question was: Is the misfit of the implant-supported zirconia CAD-CAM framework lower than that of non-Y-TZP implant-supported fixed restorations? Results: Eleven articles were included for qualitative assessment and critical appraisal in this review. In the included studies, Y-TZP CAD-CAM implant-supported frameworks were compared to Titanium (Ti), Ni-Cr, Co-Cr, PEEK and high-density polymer, and cast and CAD-CAM frameworks. The studies used scanning electron microscopy, one-screw tests, digital or optical microscopy, 3D virtual assessment, and replica techniques for analyzing the misfit of frameworks. Six studies showed comparable misfits among the Y-TZP CAD-CAM frameworks and the controls. Three studies showed higher misfits for the Y-TZP CAD-CAM frameworks, whereas two studies reported lower misfits for Y-TZP CAD-CAM implant frameworks compared to controls. Conclusion: Y-TZP CAD-CAM implant-supported frameworks have comparable misfits to other implant-supported frameworks. However, due to heterogeneity in the methodologies of the included studies, the overall numerical misfit of the frameworks assessed in the reviewed studies is debatable


Introduction
Dental implants are surgically placed devices that have direct contact with the alveolar bone [1,2]. In addition to supporting single-tooth restorations, they are also used to support and retain prostheses for the restoration of partially or completely edentulous patients [3]. Implant-supported removable and fixed prostheses possess significant advantages over conventional prostheses. In addition to offering superior support [4] and stability [5], implant-supported prostheses preserve residual bone [6] and are esthetically pleasing [7]. It has been estimated that the 5-year success-rate of implant-supported prostheses is as high as 95% [8,9].
Frameworks of implant-supported dentures have conventionally been constructed from cast metals [10]. However, cast implant-supported prostheses have several drawbacks. The clinical phase of these prostheses includes taking impressions which may become easily distorted and damaged during or after the impression-taking process [11]. In addition, the cast metal alloys may undergo distortion during the casting process, resulting in a misfit of up to 450 µm [12,13]. Moreover, the wax pattern of the cast framework may also undergo implant-supported dental prostheses; Controls: Non-Y-TZP-supported fixed restorations; Outcomes: Misfit).

Eligibility Criteria
Before conducting the literature search, eligibility criteria were decided on by the author. Prospective clinical studies, case reports and series, animal studies, and laboratory studies focusing on comparing the fit or misfit of CAD-CAM implant-supported Zirconia fixed restorations with other non-Y-TZP implant-supported restorations were included. Literature from inception to May 2022 was searched. Additionally, only articles in English were included. Studies not in the English language, systematic or literature reviews, and letters to the editor were excluded.

Literature Search
An electronic search using the keywords ((Zirconia) OR (Y-TZP) AND (Restoration or bridge or framework) AND ((computer-aided design OR CAD)) or (computer-aided manufacture) OR CAM)) AND (full arch OR partial OR complete) AND (control OR titanium OR resin OR cobalt chromium) AND (misfit OR gap OR adaptation) AND (implant)) was conducted on the following databases: PubMED/MEDLINE, ISI Web of Science/Knowledge, Scopus, Embase, and Google Scholar, including studies up to May 2022. Following the exclusion of the non-relevant articles on the basis of titles and abstracts, the full texts of studies appearing to meet the inclusion criteria were downloaded. Additionally, the reference lists of the full-text documents were scanned manually to look for relevant articles. Furthermore, a similar search was repeated using the same keywords on the clinical trial registers CONTROL and clinicaltrials.gov. The literature search was conducted by author (HA) interpedently, and any disagreements were solved by discussion with a statistician.

Data Extraction
Using predetermined items, the data from each study were extracted to construct tables. Briefly, the materials used to construct the dentures in the test and control groups (if any), the method of denture fabrication, the type of misfit (or fit) assessment employed, measurements of any other variables, and the qualitative outcomes of the studies were summarized in the first table. Summarized information on the implant or abutment system, the dimensions and positions of the dental implants, the type of implant-supported prostheses (fixed or removable, along with the number of units), the CAD-CAM fabrication system, and the numerical values of the misfit or fit was also prepared.

Quality Assessment
The overall quality of the studies and any bias present in the studies were assessed using a modified version of the 'Guidelines For Reporting Pre-Clinical In Vitro Studies On Dental Materials' developed by Mariano [40]. Briefly, in each study, the following items were assessed: an adequate abstract, introduction (background and objects), and methodology (replicability, reporting of adequate outcomes, a predetermined sample size, and details of any randomization, blinding, or concealment employed), adequate statistics, a mention of any limitations in the discussion, funding details, and, if any, the protocol of the study was accessible. A 15-point checklist was used to grade each study. Each study was assigned an overall quality of low (score: 0-5), medium (score: 6-10), or high (score: 11-15).

Results of the Literature Search
The primary literature search resulted in 105 articles. 25 articles were eliminated on the basis of titles. Of the 80 articles, 66 articles were further excluded after the review of the abstracts and on the basis of relevance. Therefore, the full texts of 14 articles were downloaded to assess their eligibility for inclusion in this review. Three full-text articles were excluded because two of them were systematic reviews [41,42] and one did not include any controls to which to compare the misfit of the Y-TZP prosthesis [43]. Hence, 11 articles were included for qualitative assessment and critical appraisal in this review [28][29][30][31][32][33][34][35][36][37][38]. The study methodology is presented in Figure 1. The overall Kappa (intra-examiner reliability) score was calculated as 0.87.
The primary literature search resulted in 105 articles. 25 articles were eliminated on the basis of titles. Of the 80 articles, 66 articles were further excluded after the review of the abstracts and on the basis of relevance. Therefore, the full texts of 14 articles were downloaded to assess their eligibility for inclusion in this review. Three full-text articles were excluded because two of them were systematic reviews [41,42] and one did not include any controls to which to compare the misfit of the Y-TZP prosthesis [43]. Hence, 11 articles were included for qualitative assessment and critical appraisal in this review [28][29][30][31][32][33][34][35][36][37][38]. The study methodology is presented in Figure 1. The overall Kappa (intra-examiner reliability) score was calculated as 0.87.

Outcomes of Included Studies
In five studies, the misfits of the Y-TZP CAD-CAM frameworks were comparable to that of Ti CAD-CAM [28,31,[35][36][37]. In one study, Ti CAD-CAM had a significantly lower misfit compared to Y-TZP CAD-CAM [38]. Compared to Co-Cr CAD-CAM, in one study, Y-TZP CAD-CAM exhibited a comparable fit [30], and in another one, Co-Cr CAD-CAM had a significantly better fit [32]. When compared to copy-milled Y-TZP and Ni-Cr CAD-CAM frameworks, Y-TZP CAD-CAM had a lower misfit in one study [29]. When compared with PEEK and resin composites, Y-TZP CAD-CAM prosthesis had a better fit [33]. On the other hand, in one study, CAD-CAM frameworks constructed from high-density polymer (HDP) had lower misfits than Y-TZP CAD-CAM frameworks [35].

Discussion
CAD-CAM prostheses provide a significant advantage over conventional cast prostheses in terms of the number of patient visits, appointment duration, and accuracy [21]. Additionally, with the application of intraoral scanning and CAD-CAM, there is no need for impression taking and study or cast model construction, making cross infection easier. The aim of this study was to critically appraise and summarize the current evidence comparing the fit of implant-supported Y-TZP CAD-CAM frameworks to that of other metal and non-metal implant frameworks. The majority of the studies included in this review concluded that implant-supported Y-TZP CAD-CAM frameworks have a better or comparable fit to that of cast and CAD-CAM frameworks constructed from Ti, Co-Cr, resin, and PEEK [28,29,31,[35][36][37].
The overall outcome of this systematic review suggests an acceptable fit accuracy of Y-TZP CAD-CAM frameworks, but this should be interpreted with caution due to the heterogeneity in the methodology and outcomes of the studies. Several different CAD-CAM systems were used to construct the frameworks [28][29][30][31][32][33][34][35][36][37][38], making the standardization and comparison of the results difficult. In eight studies, conventional CAD-CAM was used to fabricate frameworks; however, in three studies, copy-milling was employed [28,29,38]. As opposed to conventional CAD-CAM, copy-milling involves the digital scanning of a manually constructed wax or resin pattern of the prostheses. Dimensional changes in the constructed pattern may contribute to discrepancies in the misfit of prostheses constructed with this method. However, to date, no comparative studies have been conducted to assess the misfit of copy-milled Y-TZP frameworks to that of CAD-CAM frameworks. Furthermore, the types of implant abutments used to support the CAD-CAM Y-TZP frameworks [28][29][30][31][32][33][34][35][36][37][38] differed in the reviewed studies, which makes it difficult to prescribe guidelines for constructing CAD-CAM frameworks with an optimal fit or minimal misfit. Another limitation of the studies was that all of them were in vitro laboratory studies [28][29][30][31][32][33][34][35][36][37][38]. Indeed, it is difficult to measure the misfit of prostheses in vivo [44] because there are several factors that affect not only the misfit of implant-supported prostheses but also the overall lifespan of the prostheses. These factors included masticatory forces, parafunctional habits, the age of the patient, systemic health, and the osseointegration of dental implants [45][46][47][48]. Hence, future studies should attempt to simulate the effects of these factors on the misfit of Y-TZP CAD-CAM frameworks.
The differences among the methods used for the assessment of the misfit make it difficult to reach a definite conclusion regarding the misfit of Y-TZP CAD-CAM frameworks to other materials. The 'one-screw' test involves the placement of a single screw at the terminal implant abutment, and the opposing abutment is evaluated for movement radiographically or clinically. This test was used in four studies in this review [31,35,36,38]; however, its major limitation is its primary reliance on manual measurements with the naked eye, making the assessments unreliable in many cases. Indeed, this inconsistency is reflected by the results of the four studies that have compared the misfit of Y-TZP CAD-CAM to that of Ti CAD-CAM: in three studies, Y-TZP exhibited either a lower or comparable misfit [31,34,36], and in one study, Ti frameworks possessed a lower misfit [38]. Only two studies made use of CT scanning or virtual scanning to assess the misfit [34,36]. Indeed, the relatively large range of the misfit of the Y-TZP CAD-CAM frameworks (3.7 µm to 103.71 µm) is most likely due to the non-standardization of misfit assessments, so future studies should focus on reproducible and standardized techniques to compare the misfit of frameworks. Nevertheless, due to variations in the fabrication techniques, material phase, and equipment type used, attaining ideal standardization among the Y-TZP misfit studies may not be pragmatic. It is also important to note that CAD-CAM Y-TZP crowns have an approximate success rate of 70% after 24 months, and the most likely reason for this is fatigue-failure [49]. Therefore, more studies focusing on the reasons for CAD-CAM framework misfit and the resultant failures should be conducted. Nevertheless, a recent retrospective clinical study on implant-supported CAD-CAM Y-TZP denture frameworks provided to 50 patients found no long-term failures after 2 years, which makes the long-term viability of Y-TZP CAD-CAM frameworks promising [50]. Nevertheless, for the adequate functionality and survival of implant-supported prostheses, optimal oral hygiene is vital, and patients should be educated about this during and after treatment [51].
In addition to the above concerns, there were multiple sources of bias found in the studies. A pre-determined sample size was used in only two studies [31,32], and the sample sizes in the remaining studies may have not been sufficient to produce reliable results. Furthermore, no study mentioned any attempt in blinding the investigators or technicians during the experiments. Although it is difficult to blind the investigators from the materials due to their difference in appearance, it may be possible to blind the experimental groups corresponding to the measurements of the misfit assessments in future studies. In the majority of the studies, randomization was not attempted, which may have contributed to selection bias within the studies. A major limitation of this systematic review itself was that it was not possible to conduct a meta-analysis because of the heterogeneity of the studies included. Thus, it was not possible to deduce an overall misfit effect of the results. Therefore, to achieve a certain level of standardization among the misfit evaluation investigations, further studies should incorporate blinding, randomization, similar misfit evaluation methods, and analyzed sample sizes.
In addition to CAD-CAM Zirconia frameworks, the 3D printing of such denture frameworks may provide an additional advantage of additive manufacturing leading to the reduced wastage of material and reduced costs [52]. Nevertheless, a lack of clinical trials or other prospective studies to assess the misfit of the Y-TZP CAD-CAM means that, to date, it is difficult to ascertain whether the misfit of these frameworks is lower or comparable to other types of frameworks. Consequently, large-scale clinical studies and standardized in vitro studies with minimal bias are necessary to make a more definite conclusion.

Conclusions
Within the limitations of this review and the included studies, it may be concluded that Y-TZP CAD-CAM implant-supported frameworks have a comparable misfit to other CAD-CAM implant-supported frameworks. However, due to the heterogeneity in the methodologies of the included studies, the overall numerical misfit of the frameworks tested in the studies is debatable. Better-designed in vitro and long-term clinical studies are required to reach a more definite conclusion.
Funding: The research did not receive any funding.

Institutional Review Board Statement: Not applicable (Review study).
Informed Consent Statement: Informed consent was not needed, as it is a review study.

Data Availability Statement:
The data are available upon request from the author.