Transfer Accuracy of 3D-Printed Customized Devices in Digital Indirect Bonding: A Systematic Review and Meta-Analysis

Aim To evaluate in vitro and in vivo the accuracy of 3D-printed customized transfer devices during indirect bonding technique (IBT). Methods A search for articles published in the English language until April 2022 was carried out using PubMed, Web of Science, Scopus, and Google Scholar databases and by applying a specific search strategy for each database to identify all potentially relevant in vivo or in vitro studies. After the removal of duplicate articles and data extraction according to the participants-intervention-comparison-outcome-study design schema scheme, the methodological quality of the included studies was assessed using the Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies. Results The initial search identified 126 articles, 43 of which were selected by title and abstract. After full-text reading, 15 papers were selected for the qualitative analysis and seven studies for the quantitative analysis. The evidence quality for the selected studies was moderate. Conclusions Except for the bucco-lingual direction, the 3D-printed customized devices have a transfer accuracy within the clinically acceptable limits established by the American Board of Orthodontics. Therefore, 3D-printed transfer devices may be considered an accurate method for bonding position during IBT, both in vitro and in vivo. Additional randomized clinical studies in vivo should be suggested.


Introduction
The accurate positioning of brackets is a critical factor in orthodontic treatment since the introduction of the straight-wire technique [1], as it can affect the results and duration of the overall therapy [2].Therefore, achieving correct bracket positioning is crucial to attain the best possible outcome [3].Orthodontic brackets can be placed on the tooth surface through either direct or indirect bonding methods.The direct bonding method consists of a one-step procedure, which involves the direct chair-side placement of brackets onto the enamel surface [4].Although direct bonding is the most commonly used method, Silverman et al. [5] introduced the indirect bonding technique (IBT) in 1972.This technique was developed to optimize the accuracy of bracket positioning, as the ideal bracket positions are planned through a laboratory process in IBT [5].In this technique, brackets were placed on dental casts and then bonded to the patients' teeth using a transfer device [6].Therefore, the IBT allows for the reduction of clinical chair time and improvement in accuracy in bracket placement compared to the direct bonding technique [7].In fact, the IBT decreases positioning errors due to clinical limitations such as low visibility, limited mouth opening, excessive salivary flow, or patient collaboration [8].Moreover, during IBT, the reduced salivary contamination and limited chair time enable the containment of aerosol production and minimize personal contact, which are key factors in preventing contamination during orthodontic procedures [9,10].
However, among the disadvantages of IBT, there are the difficulties of the inner technical procedures, which are related to the professional experience of the operator (including recording of alginate impressions and fabricating of dental casts and transfer trays).Moreover, IBT is associated with higher overall time and cost of laboratory procedures compared to the direct bonding technique [11,12].
Computer-aided design and computer-aided manufacturing (CAD/CAM) technology have recently been introduced in orthodontic practice [2], and digital indirect bonding has emerged as a viable alternative to the traditional method, overpassing its complicated manual laboratory process with a digital workflow [13].
According to the literature, the use of an intraoral scanner and the virtual bracket setup has been shown to increase the accuracy of bracket positioning rather than using conventional impressions and manually placing brackets on plaster models, respectively [11].
However, bonding accuracy depends on the absence of discrepancies between the transferred position of orthodontic brackets and their virtual planned placement [14].Therefore, the transfer devices are key factors in this process.In fact, in the traditional approach, the use of conventional materials could influence the bracket placement, reducing bonding accuracy during production, transfer, and removal of these transfer devices [15].
Actually, instead of conventional materials, clinicians may design and fabricate 3D-printed devices to transfer the virtual planned bracket position to the teeth [6].
In literature, different types of transfer devices have been proposed using 3D printing technology [16].
In addition to time and cost saving [12], the use of 3Dprinted trays appears to reduce human error during laboratory steps, increasing the fit of the trays on teeth compared to traditional handwork and improving the precision of the indirect bonding [2].
However, the selection of 3D-printed materials and the design options of the tray are critical variables that may influence the accuracy of the digital indirect bonding [17].
In literature, a recent review conducted by Bakdach and Hadad [18] has analyzed the accuracy of 3D-printed transfer trays for indirect bonding, concluding that 3D-printed trays have an acceptable transfer accuracy.However, although this review [18] was published in March 2022, the articles search has been ended in August 2021, omitting a large number of studies conducted more recently [4,11,13,17,[19][20][21][22].
Therefore, given the relevance of this topic and given the large amount of techniques currently available for tray design and 3D-printing, an update of the existing literature [18] needs to be done to upgrade the evidence-based efficacy of the IBT with 3D-printing technology.

Aim
Therefore, the aim of this systematic review was to evaluate the accuracy of 3D-printed transfer devices during IBT to answer the following questions: (i) What is the accuracy of 3D-printed transfer devices in linear and angular measurements?(ii) Are there any differences between their design and 3D-printing characteristics?(iii) What is their accuracy in vivo?

Material and Methods
The present systematic review adhered to the PRISMA statement [23].The protocol of this systematic review was preliminarily registered on PROSPERO (ID: CRD42022319757).
The study selection, the data collection, and the quality assessment were independently performed by two authors (A.C. and E.L.M.).Conflicts were resolved by discussion with a third author (L.L.M.).The level of agreement between the two reviewers was assessed using Cohen kappa statistics.
3.1.Eligibility Criteria.According to the participants-intervention-comparison-outcome-study design schema (PICOS), the inclusion and exclusion criteria are summarized in Table 1.

Information Sources and Search
Strategy.The search for articles was carried out using four electronic databases (Table 2) and included publications in the English language until April 2022.A specific search strategy was developed for each database, as shown in Table 2.In addition, the reference and citation lists of the included trials and relevant reviews were manually searched.

Study Selection and Data Collection
Process.All titles identified from the literature were screened and selected, following the inclusion and exclusion criteria.Duplicate studies were preliminarily excluded.The abstracts were examined, and the full texts of the remaining articles were assessed for eligibility before inclusion in the final analysis.
3.4.Data Items.The characteristics of the included studies (author, journal/year, study design, groups, type of transfer device, transfer design, initial teeth analyzed, final teeth analyzed, scanner, software for bracket positioning, software for tray design, 3D-printer, resin, bracket, bonding materials, software for superimposition, superimposition technique, main outcome, clinical relevance).
3.5.Methodological Quality Assessment.The Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies (SBU) was used to evaluate the methodological quality of the studies included in this review [24].The articles were categorized into three levels (A, B, and C) of evidence based on the following criteria: After assigning a score to each study, the available evidence in the review was further classified into four grades: (1) Strong: at least two studies of level "A." (2) Moderate: one study of level "A" and at least two studies of level "B." (3) Limited: at least two studies of level "B." (4) Scarce: fewer than two studies of level "B." 3.6.Synthesis of Results.A meta-analysis was performed using Review Manager 5.4 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011) to evaluate the transfer error of 3D-printed transfer tray in all dimensions (mesio-distal, occluso-gingival, bucco-lingual, torque, tip, and rotation).A random-effects model was used to accommodate heterogeneity across studies and mean differences with 95% confidence intervals and standard errors were considered for all evaluated outcomes.Statistical heterogeneity was assessed by the χ 2 -square test and the I 2 index.When I 2 was between 0% and 50%, the heterogeneity was considered low; when I 2 was above 50%, the heterogeneity was defined as high.After removing duplicate studies and those that did not meet the eligibility criteria based on title and abstract, a total of 43 full-text articles were screened.Finally, a total of 15 papers were identified for the qualitative analysis according to the eligibility criteria.Seven studies were selected for the quantitative analysis.
The flowchart of the selection of eligible studies for this review is summarized in Figure 1.

Assessment of Methodological Quality of Individual
Studies.According to the SBU tool, the quality of evidence for one study [25] was high, and for two studies [16,19] was moderate (Grade B).As a result, the level of evidence for the conclusions of this review was considered limited (level 3).The other included studies were laboratory studies.

Discussion
5.1.Summary of Evidence.The aim of this systematic review was to evaluate the accuracy of the bonding position during IBT with 3D-printed transfer devices by assessing the linear and angular discrepancies between the transferred position of orthodontic brackets and their virtual planned placement.
Despite the satisfactory results achieved with the digital indirect approach, over the several CAD/CAM indirect bonding systems have been introduced [16,18], and a range of transfer devices based on digital methods have become available to clinicians [2,4,11,13,16,17,[19][20][21].
Transfer trays can be produced by 3D-printing a model with virtual planned brackets, using either traditional materials like silicone or thermoplastics, or by designing and directly manufacturing them through a 3D-printing process [16].
Many in vitro studies have compared the accuracy of 3Dprinted trays produced with CAD/CAM technology to traditional systems [3,6,7,22,25,26].Chaudary et al. [25] observed greater accuracy with 3D-printed trays compared to silicone devices, except in the vertical dimension.Pottier et al. [7] also reported that, although silicone trays showed higher precision, both digital and conventional methods were considered clinically acceptable.
Both 3D-printed devices and vacuum-formed trays demonstrated comparable precision according to several studies [3,6,22,26].However, Zhang et al. [22] found that the conventional approach had the advantages of shorter fabrication time and lower costs.
The development of CAD/CAM software has simplified the virtual planning of the bracket position on digital casts, as well as the design and fabrication of customized 3D-printed devices to transfer the virtual planned bracket position from the 3D software to the teeth [6], making the indirect bonding procedure less reliant on operator experience [2].
According to Rattanasumawong et al. [26], using a digital workflow for designing and 3D-printing transfer trays not only saves time and costs [12] but also reduces the occurrence of human error during laboratory procedures, resulting in a superior fit of trays on teeth compared to conventional manual techniques and enhancing the precision of IBT [2].
Advancements in technology have significantly improved the precision of methods used to measure the accuracy of IBT, mainly due to the increased sensitivity of modern scanners and upgraded 3D software that enables virtual  International Journal of Dentistry bracket positioning, tray design, and 3D image superimposition [7].
However, the accuracy of 3D superimposition programs can also be influenced by the technique used [18].
In the past, analyzing positioning errors relied on 2D photographs, which had limitations due to the operator's sensitivity [2].Nowadays, 3D superimposition has replaced the 2D approach, and a wide range of 3D techniques are available to assess bracket positioning accuracy using 3Dprinted transfer trays [7].Clinicians typically use the local best-fit algorithm to superimpose specific dental surfaces with corresponding brackets [2,4,6,7,11,13,16,17,[19][20][21][22]26] or excluding brackets [3,25], but transfer errors may occur if there is insufficient data in digital scans, such as in the contact surfaces between misaligned teeth [18].
Some studies have used digital bracket templates to superimpose scanned brackets [3,16], but this method was less accurate due to the error within the method itself, as the surfaces of the matched brackets were not identical, and this led to inaccuracies in the calculation.
In addition to the increased accuracy of the overall 3Dprinting workflow technique, other factors that may affect the accuracy of 3D-printed transfer trays include the type of printer and 3D-printed materials selected, tray design options, and clinical bonding procedures [17,30].
Different 3D printing technologies are available for manufacturing 3D-printed devices, including stereolithography (SLA), the photo jet process, and digital light processing (DLP) [31].
SLA uses a laser to cure a light-sensitive polymer layer by layer in a vat of liquid polymer, while the photo jet process uses an inkjet print head to jet a light-sensitive polymer onto a build platform and cure it layer by layer.DLP cures liquid resin layer by layer using a projector light source, building the object upside down on a progressive elevating platform [31].
Several studies suggest that the positioning of dental models on the build platform of a 3D printer can affect the precision of the 3D-printed object [32].As a result, various ideal printing directions have been proposed over the years.Hada et al. [33] and Unkovskiy et al. [34] reported that an angulation of 45°is the best orientation, while Shim et al. [35] identified 90°as the orientation for the most accurate manufacturing.Süpple et al. [32] reported that using DLP printers, the printing orientation on the build platform did not significantly affect the transfer accuracy.
Zhang et al. [36] found that for DLP technology, the optimal layer thickness was 50 μm, although high printing accuracy was also achieved with a layer thickness of 100 μm.They also found that for SLA technology, the printing accuracy increased with decreasing layer thickness.
Additionally, Arnold et al. [37] demonstrated that the placement of objects on the build platform of SLA printers can affect accuracy.They reported that the most accurate object was printed in the front of the platform, which contrasts with Unkovskiy et al. [34], who found that objects placed in the center of the build platform were more accurate than those placed at the border.
The rigid-flexible characteristics of the 3D-printed materials can also affect the accuracy of transfer trays.Only Hoffman et al. [17] compared the accuracy of two types of 3D-printable resins, reporting better accuracy with Dreve resin compared to Next Dent resin.They concluded that transfer errors can be reduced by using an appropriate 3D-printing tray.
Jungbauer et al. [20] demonstrated in vitro that the hardness of the printing materials can affect the bracket transfer accuracy, particularly in angular measurements.
While hard materials can result in an incomplete fit of the tray on dental surfaces or immediate bracket debonding during tray removal [12,38], elastic characteristics can cause a tray distortion due to the pressure of the clinician's fingers, leading to overseating of the transfer devices and bracket positioning errors [8].Therefore, it is important to design the parts of the tray that cover the brackets with the exact dimensions of each bracket to ensure appropriate retention during transfer and precise control during tray positioning [6,7,17].Additionally, the design should allow for easy removal after bracket bonding to minimize the risk of debonding during tray removal [6].These considerations are supported by research conducted by various authors [6-8, 12, 17].
To overcome these limitations, several authors have suggested alternative tray designs, such as partially covering the dental surfaces [16,20], incorporating different retention mechanisms (e.g., arm-like sleeves, pocket-shaped designs) [21] or customized resin bases [27], or using a double-layer design with as ofter inside layer and a harder outside layer [6].
As suggested by De Oliveira et al. [14], bonding errors can also occur during clinical bonding procedures.Variations in the thickness of the bonding materials may result in insufficient or excessive adhesive application, leading to inaccurate positioning of the brackets on the teeth [16].However, the use of transparent printable resin allows for intraoral checking of the tray fit and enhances the penetration of curing light during brackets polymerization, ultimately reducing the incidence of bonding failures, which is one of the most frequently reported disadvantages of IBT in the literature [12,39].
Among clinical variables, the size and the shape of the teeth may affect the accuracy of transfer trays [13].As reported by Kim et al. [2], the cusp height of posterior teeth did not affect the accuracy of both linear and angular measurements, in contrast to Jungbauer et al. [20], in which torque errors were more frequent at crowded frontal teeth.In addition, the use of resin base for individual teeth did not increase the accuracy, as reported by Park et al. [13].
The signs (positive or negative) of the values indicated the direction of bonding displacement in relation to the reference position of each coordinate [13,23].Positive values International Journal of Dentistry indicated errors such as mesial, buccal, or gingival deviation, or more lingual torque, distal angulation, or mesial rotation of teeth compared to the planned position.
The direction of bonding displacement was expressed through positive or negative values [16,25]; for example, positive values indicated errors such as mesial, buccal, or gingival deviation, or more lingual torque, distal angulation, or mesial rotation of teeth compared to the planned position.
The results of the present study indicated that the overall mean transfer error was within an acceptable range.The higher inaccuracy was observed in the buccal direction (0.11°), followed by gingival (0.09 mm) and by mesial (0.07 mm) directions.
Regarding angular measurements, the highest transfer errors were 2.04°for lingual torque, 1.20°for the distal tip and 0.96°for mesial rotation.
Positioning errors may affect treatment goals, and the literature has reported that linear errors less than 0.5 mm and angular errors less than 2°are considered clinically acceptable.However, over this value, teeth alignment and positioning of marginal ridges could be negatively influenced, as established by the American Board of Orthodontics [40].
Among the included studies, only a few studies have evaluated the accuracy of virtual bonding in the oral cavity using 3D-printed transfer trays in vivo [16,19,25], while most of the available studies have been performed in vitro on experimental dental casts [2-4, 6, 7, 11, 17, 21, 22, 26, 27].
However, the intraoral scanning procedure has been associated with a higher number of errors compared to laboratory model scans due to interference from salivary and soft tissues and lower lighting conditions, especially in the posterior region [2].
The maximum linear inaccuracy of incisors in the buccolingual direction may be explained by an improper fit of the tray caused by either a lack or an excessive pressure applied on the tray during IBT, especially when the brackets are not completely covered within the tray to facilitate its removal after bonding procedures [18].
Futhermore, the maximum inaccuracy in torque and tip could be influenced by the amount of the adhesive at the base of brackets [25], as an increased adhesive thickness or incorrect pressure applied on the tray due to the reduced visual check of the tray fit in the posterior region may affect the accuracy of bonding positioning [2,6,16].In addition, placement errors at the premolars could also be due to the lack of precision of transfer devices in terminal areas [7] or to errors during scan data acquisition or during the tray fabrication process, which could affect the accuracy of IBT.However, except for the bucco-lingual direction, all linear and angular measurements were within clinically acceptable limits.Therefore, in vivo, the use of 3D-printed transfer devices may be used for accurate IBT in vivo.

Conclusions
According to the SBU tool, the present review may draw conclusions reflecting a limited level of evidence.
(i) 3D-printed customized devices can be considered an accurate system for bonding position during IBT in both linear and angular measurements, both in vivo and in vitro.(ii) In vitro, the highest transfer error was reported in the bucco-lingual direction for linear measurements and in torque for angular measurements.(iii) In vivo, the highest transfer inaccuracy was reported in the bucco-lingual direction at the incisor level (for linear measurements) and in torque and tip of premolars (for angular measurements).However, the transfer accuracy of 3D-printed customized transfer trays appears to be within the clinically acceptable limits reported by the American Board of Orthodontics, except in the bucco-lingual direction.
Additional randomized clinical studies should be conducted to further assess the in vivo accuracy (possibly using standardized adhesive thickness during bonding procedures) and to evaluate the reproducibility of the IBT with 3Dprinted transfer devices by different clinicians with varying clinical experiences.

FIGURE 3 :
FIGURE 3: Forest plot comparing the transfer inaccuracy on of the 3D-printed transfer trays in vivo.(a) Transfer accuracy on incisors; (b) on canines; (c) on premolars.CI, confidence interval; IV, inverse variance; SE, standard error.

TABLE 1 :
List of inclusion and exclusion criteria, according to PICOS schema.

TABLE 2 :
Database, search strategies, and results.

TABLE 3 :
Characteristics of the included studies (I).

TABLE 4 :
Characteristics of the included studies (II).