The goal of this randomised clinical trial study is to investigate 3D-printed shape memory aligners in the treatment of anterior dental open bite adult patients. The main questions it aims to answer are:

1. Do 3D-direct-printed shape memory aligners demonstrate potentiality in the management of AOB?
2. What is the effect of 3D-direct printed shape memory aligners on molar intrusion?
3. Can the 3D-direct printed shape memory aligners extrude anterior teeth without the use of attachments?
4. Do 3D-direct printed shape memory aligners generate greater/higher stress distribution and initial teeth displacement compared to conventional clear aligners? Researchers will compare three groups: Group I: Patients treated with conventional clear aligners with attachments; Group II: Patients treated with 3D direct-printed shape-memory aligner without attachment; Group III: Patients treated with 3D direct-printed shape memory clear aligners with attachments and see its effect on anterior open bite treatment.

Participants will wear a clear aligner for about 6-8 months. Then

3.0 Material and methods 3.1 Ethical approval Ethical clearance will be obtained from the Medical Ethics Committee, Faculty of Medicine, University of Kufa, Iraq (MEC-163). This randomised clinical trial will be registered and reported at clinicaltrials.gov, among Class I molars and skeletal relationships with anterior dental open bite Iraqi patients.

3.2 Sample size calculation: Sample size calculations were performed. In each group, a sample size will be calculated by G-power (version 3.1), at a power of 80% and a 0.05 level of significance, which enabled the detection of significance between the three treatment groups in overbite changes of 1.5 mm with a standard deviation of 1.5. The final anterior open bite sample consisted of 15 patients for each group. To account for a potential 10% dropout rate, two individuals will be added to each group, resulting in a final sample size of 51 individuals-17 per group, according to a previous study done by Serdar et al. (52).

3.3 Participants, eligibility criteria, and settings: Patients will be recruited from the Department of P.O.P., University of Kufa, Azadi Dental Centre, and a private dental clinic located in Iraq. The treatment will be done by a specialist orthodontist. Patients will be recruited at the time of their consultation if they meet the study criteria: Table (3.1).

Table 3.1: Study criteria.

The inclusion criteria: The exclusion criteria:

1. Adult patients, age 18-35 years, all teeth present and fully erupted (excluding third molars) Adults have completed craniofacial growth, which makes orthodontic movements more predictable and stable; Adults are typically more motivated and compliant with the 20-22 hours/day wear time, essential for treatment success (not forgetting to wear them, reducing effectiveness). Moreover, in mixed dentition there will be teeth eruption and exfoliation that could be effect on the aligner fitting and accuracy] (53,54).
2. Mild-moderate dental anterior open bite (-1 to 3 mm vertical gap between the incisal edge of upper and lower incisors).
3. Angle Class I molar relationship.
4. Skeletal Class I (ANB 3±2°).
5. Average (normodivergent) vertical dimension (MMPA 27±5°).
6. Healthy periodontal status.
7. Well-aligned or mildly crowded dentition.
8. Patients should be treated with incisor extrusion (upper only or both).

(1) Moderate to severe crowding. (2) Loss of posterior teeth. (3) History of trauma to the molars or incisors. (4) History of endodontic treatment to the maxillary first molar or incisors. (5) Systemic disease related to bone metabolism. (6) Taking immunosuppressive drugs or drugs inhibiting or accelerating tooth movement; and (7) Neuromuscular deficiencies. (8) Skeletal open bite. (9) Short upper lip. (10) Average or increased incisors show. (11) treatment plan requiring surgery or extraction of any maxillary teeth. (12) severely rotated or heavily restored (direct or indirect restoration) maxillary anterior teeth 3.3.1 Interventions: All patients will be received the same treatment and will be a signed informed consent to participate in the study. The patient intervention will be summarized as following timeline flow chart: (Figure 3.1).

Figure 3.1: Patient intervention timeline flow chart.

1. Before aligner insertion (T0):

   1. Open bite measurement: Will use digital software (3Shape OrthoAnalyzer) from the incisor's edges of upper and lower central incisors, also; clinically using digital clipper (Kroeplin Caliper, Germany) (54).
   2. CBCT records: CBCT radiography will be done for each patient after signing the informed consent. All the patients will take a CBCT (T0) (80 kV, 5 mA, 9.2 s exposure time, 0.125 mm voxel resolution, 80 x 80 mm field of view; Veraviewepocs J Morita MPG, Fushimi, Kyoto, Japan). CBCT images will be reconstructed every 0.125 mm. One Volume Viewer Software (Version 11.0, J Morita, Chatsworth, CA, USA) will be taken before treatment (T0) and after the first series of aligners (15-20 aligners) (T1).
   3. Intraoral scanner: An intraoral scanner (TRIOS, 3Shape, Copenhagen, Denmark) will be used to scan the upper and lower jaws with occlusion, also to render an STL file, which will be imported to the 3Shape OrthoAnalyzer (USA), that will be used to design each patient's treatment sequence and will be taken before (T0) treatment.

2. Aligner and attachment setting:

   1. Attachment bonding: The protocol for attachment bonding was standardised using the commonly accepted bonding procedures. Attachments and IPR were tailored to each patient's needs, based on each of the three practitioners' clinical experience. Therefore, attachment location and IPR on teeth cannot be reported systematically.
   2. Composite attachment position: The incisal margin of the composite attachments will be placed 3.5 mm gingivally to the incisal edge. Both mesial and distal margins of the composite attachments were 2.5 mm away from the mesial and distal surfaces of the tooth and will be designed to be 4 mm wide mesiodistally; the incisogingival dimension and the angulation were unaltered (55).
   3. Aligner insertion: Proper demonstration of aligner insertion as instructed will be observed. Participants will verbally confirm compliance at each appointment, and compliance will be self-recorded by participants in hours per day.
   4. Aligner wearing time: Patients will be instructed to wear each aligner for a minimum of 22 h/d, 7 d/wk each, before moving to the next aligner, the standard aligner protocol used by the participating providers (55).
   5. Movement limit: The movement (extrusion) limit will be set to 0.25 mm maximum per aligner (55).

3. After the first series of aligners (15-20 aligners) (T1):

All the records that have been taken before treatment (open bite measurement, CBCT (T1), intraoral scanner) will be taken after the first series of aligners (15-20 aligners by the same criteria as before treatment.

3.3.2 Interim analysis and stopping guidelines: Participants will be informed that they could discontinue participation at any time and that it would not affect their remaining treatment. Patients with poor tracking requiring midcourse intervention or failure to complete the aligners prescribed will be noted for reporting purposes but not included in the final analysis.

3.4 Study design and grouping: The study design will be a multicentre randomised clinical trial with three parallel arms.

Three groups of participants with different treatments will be tested in the present study as follows:

Group I: Patients treated with conventional clear aligners with attachments [rectangular-shaped attachments with bevelled edges toward the gingiva on anterior upper and lower teeth (53)].

Group II: Patients treated with 3D direct-printed shape-memory aligner without attachment, and Group III: Patients treated with 3D direct-printed shape memory clear aligners with attachments [rectangular-shaped attachments with bevelled edges toward the gingiva on anterior upper and lower teeth (53)].

3.5 Treatment duration: The treatment duration for each patient will be about 8-14 months, and the general study time will take about 3 years to complete.

3.6 Digital impression-taking technique and appliance fabrication: 3.6.1 Thermoforming on the 3D-printed models: The conventional thermoforming technique is indirect in nature. After treatment planning, sequential dental models representing the patient's treatment progress will be printed after digital impression scanning of the upper and lower jaws and taking occlusion using an intraoral digital scanner (Trios, 3Shape, Copenhagen, Denmark); the thermally manipulated transparent plastic sheets (Tristar, 0.75 mm thickness, Australia) will be moulded against each dental model (3shape orthoanalyser, 1.9 software, Denmark-LINIZ printer, Seoul, Korea) by a pressure- or vacuum-forming machine (BioStar, Germany) for aligner production. The retrieved aligners will be trimmed and finished for patient delivery and insertion (Figure 3.2).

Figure 3.2 : schematic diagram of the laboratory technique to fabricate the conventional thermoformed clear aligner.

3.6.2 Direct 3D printing shape memory aligners: The direct 3D printing technique designs and fabricates the aligner directly using biocompatible clear resins (Tera Harz TC-85 (Graphy, Seoul, South Korea)) without requiring a dental model. The digital orthodontic workflow of 3D-printed aligners The sequential steps encompassing the process of direct 3D-printed clear aligner manufacturing are: (i) data acquisition using intraoral digital scanning (Trios, 3Shape, Copenhagen, Denmark), (ii) virtual planning (3D models) and computer-aided designing of clear aligners (3shape orthoanalyser, 1.9 software, Denmark), (iii) 3D printing (LINIZ, developed by Graphy 0.75 mm thickness, Inc., Seoul, Korea), and (iv) post-processing (cleaning the uncured residual resin, support removal, and post-production curing; for the Tera Harz TC-85 aligners, recommendations mention the process of cleaning by centrifugation (Tera Harz Spinner developed by Graphy, Inc., Seoul, Korea) for around 3-4 min or removal with a soft scraper). This will be followed by support removal and post-production curing with Cure M (Graphy, Seoul, Korea). The nitrogen generation curing unit (Tera Harz cure developed by Graphy, Inc., Seoul, Korea) will be utilised and recommended to enhance the physical properties of the resin material by providing an inert environment, thereby preventing the formation of an oxygen inhibition layer. The THC 2 UV Curing system (Graphy Inc., Seoul, Korea) is a known representation of this category. For the Dental LT-clear resin aligners, washing by ultrasonication with isopropyl alcohol (96/99%) and postproduction curing with the Form Cure unit (Formlabs, Somerville, Mass., USA) (24, 34, 38) are undertaken (Figure 3.3).

Figure 3.3: schematic diagram of the laboratory technique to fabricate the 3D-direct printed memory shape aligner 3.7 Finite Element Analysis (FEA):

The workflow chart to obtain results of finite element analysis (Figure 3.4):

Figure (3.4): schematic diagram of the workflow chart to obtain results of finite element analysis.

This study will be approved by the Medical Ethics Committee, Faculty of Medicine, University of Kufa, Iraq (MEC-163). A 3D geometric model will be prepared of a maxilla arch that includes the maxilla, periodontal ligament (PDL), upper teeth with the upper right central incisor intruded, clear aligners, and composite attachments (Figure 3.5a). The maxilla and upper teeth will be constructed from cone-beam computed tomography (CBCT) data of a patient who had an Angle Class I skeletal relationship with well-aligned teeth and normal tooth shape. The CBCT image will be taken with a 3D Accuitomo 170 (J. Morita Mfg. Corp., Kyoto, Japan) using an FOV of 170 mm × 120 mm and a voxel size of 0.25 mm. The image will be imported into ITK-SNAP software (51) to generate the 3D geometric model with a high-resolution FE model for simulations. The PDL will be modelled on the root shape with a thickness of 0.25 mm (52). A rectangular bevelled shape of composite attachments (Figure 3.6) will be constructed on the upper right central incisor with the shape derived from the Invisalign® system (53). Specifically, the incisal margin of the composite attachments will be placed 3.5 mm gingivally to the incisal edge (54). Both mesial and distal margins of the composite attachments were 2.5 mm away from the mesial and distal surfaces of the tooth, respectively. The clear aligners (conventional and 3D direct-printed clear aligners) will be made based on the target dentition to perform upper central incisor extrusion. Target dentition will be developed by extrusion of the upper right central incisor and composite attachment with a 0.15 mm displacement along the tooth axis (55). After that, the clear aligners will develop from an external offset of all teeth crowns and attachments at the target dentition. Clear aligner thickness was set at 0.75 mm with a scalloped trimline margin, precisely following the gingival contour of the teeth (56). To minimise the effect of upper incisor angulation on experimental outcomes, maxillary central incisors were adjusted to a 90° orientation during reconstruction.

Finally, three models will be designed as follows:

Model 1: no composite attachment with 3D direct-printed shape memory clear aligner.

Model 2: rectangular bevelled attachment with 3D direct-printed shape memory clear aligner.

Model 3: rectangular bevelled attachment with conventional clear aligner. The meshing process will produce a total of 1,467,263 nodes and 5,338,190 elements in a model without a composite attachment and 1,472,483 nodes and 5,355,482 elements in a model with a rectangular bevelled attachment (Figure 3.5b). Bonded contacts will be set at the interfaces between the bone and PDL, PDL and teeth, and teeth and composite attachment. Surface-to-surface contact will be used between the clear aligner and teeth as well as the clear aligner and the composite attachment. Fixed supports were applied on the upper part of the maxilla. A friction coefficient of µ = 0.2 was used between the aligner and teeth as well as the aligner and the composite attachment. Table (3.2) shows the material properties and mesh size that will be used in this study (Jedliński et al. (53)). The finite element analysis will proceed before the clinical trial according to the selection criteria and standardisation to establish common procedures for model creation, data exchange, and validation to ensure model quality, reliability, and consistency across different software and users.

Table 3.2: Material properties and mesh size.

Figure 3.5: Maxilla model with PDL, upper teeth, clear aligner, and composite attachment: (a) 3D model and (b) finite element meshing models.

Figure 3.6: Dimensions of the rectangular beveled attachment. An anatomical coordinate system will be established by defining the occlusal plane using reference points at the incisal edges of central incisors and the mesiobuccal cusp tips of first molars. The X-axis (coronal plane) will be orientated positively toward the mesial aspect, the Y-axis (sagittal plane) positively toward the lingual aspect, and the Z-axis (vertical plane) positively toward the gingival direction. Sequential and simultaneous extrusion movements of maxillary central incisor teeth will be simulated. Clear aligners will be applied with an extrusive force corresponding to a displacement of 0.15 mm along the long axis of the teeth. Reaction forces resulting from each extrusive method will be calculated using ITK-SNAP software after applying the preset displacement of 0.15 mm to the aligners (56). Forces equal in magnitude to these reaction forces will then be applied to the corresponding teeth to evaluate initial displacement and PDL stress distribution.

Therefore, this study will aim to evaluate the initial tooth displacement and stress distribution generated during central incisor extrusion with conventional clear aligners (with attachments) and 3D direct printed shape memory aligners (with and without attachments).

3.8 Clinical trial 3.8.1 Randomisation and Blinding: The randomisation sequence will be generated using randomisation software (sealed envelope) with a 1:1:1 allocation ratio using block randomisation. The allocation sequence will be concealed from the investigator with sequentially numbered, opaque, and sealed envelopes. Operator and subject blinding will not be possible due to the nature of the intervention. The data will be coded and presented to the blinded evaluator. All subjects will be randomised into conventional and 3D direct-printed shape memory aligner groups (with or without attachment). All data will be collected at two time points: pretreatment (T0) and after the treatment (the first series of aligners (15-20 aligners) (T1)). The dental and skeletal changes were recorded by lateral cephalograms (Dolphin software, USA). Maxillary first molar intrusion will be recorded by cone-beam computed tomography (CBCT), and force distribution and initial tooth displacement will be recorded by a finite element analysis program.

3.8.2 Outcome measurement: Outcomes and any changes after trial commencement, midcourse interventions to improve tracking, such as rescanning or introducing auxiliary appliances, will be recorded and reported, but the teeth involved will not be analysed as part of the corresponding group. Maxillary and/or mandibular incisors not tracking, noted by a minimum of 1 mm of aligner material incisally when the aligner was fully seated, will be recorded and reported but not analysed within the group assigned (56). Patients will be evaluated only after the first series of aligners (15-20 aligners (T1)). After that, treatment proceeded as necessary, determined by patients and individual practitioners, and was not recorded (57). Maxillary and mandibular arches will be evaluated in this study.

3.8.2.1 Processing and data collection (cephalometric tracing): DICOM (Digital Imaging and Communications in Medicine) files will be reoriented to standardise head position and converted into Nearly Raw Raster Data (NRRD) format using ITK-SNAP software, version 3.8.0 (University of Pennsylvania, https://www.itksnap.org). The converted files will be uploaded to 3D Slicer software, version 5.2.2 (https://www.slicer.org/), an open-source 3D medical image viewing software. 3D models of the scans will be rendered using the "Segment editor" module, and the view layout will be set to "four-up" mode to simultaneously display the 3D rendering along with the three orthogonal views (sagittal, coronal, and axial). The 3D view facilitated confirmation of landmarks' positions in the spatial space (58). Cephalometric analysis pre-treatment (T0) and post-treatment (T1) (after the first series of aligners (15-20 aligners)) lateral cephalograms will be imported into Dolphin Imaging™ software. Cephalometric landmark location measurements (linear and angular) Landmark points will be initially identified and approximated in the sagittal view by scrolling through the slices, then will be refined in the coronal and axial views. Final positional confirmation will be done on the 3D model when visualisation of the landmark is possible (59). This standardised viewing sequence will be implemented to enhance consistency across the cases, and superimpositions will be independently performed using Dolphin Imaging™ by two orthodontic faculty members. Following anterior cranial base, maxillary, and mandibular structural superimpositions, three reference planes (S-N, ANS-PNS, and Go-Me) were transferred from the T0 tracing to the T1 tracing. Eight cephalometric measurements were generated by the computer operations in Dolphin Imaging™ (Figure 3.6). The average values of estimates derived by the two orthodontists were used.

3.8.2.2 Measurement variable outcomes will be as follows:

1. Dental and skeletal leaners and angular changes (Figure 3.7): The cephalometric analysis will include the following:(1) Overbite (the overlap of the anterior teeth in the vertical dimension); (2) U1 to palatal plane angle (the inclination of the maxillary central incisor relative to the palatal plane); (3) L1 to mandibular plane angle (IMPA) (the angle formed by the long axis of the lower incisor (L1) and the mandibular plane); (4) Interincisal angle. (The relative spatial position along the long axis of the most prominent (anteriorly positioned) maxillary and mandibular central incisors); (5) U6 to palatal plane distance (Represents the perpendicular distance from the mesiobuccally cusp of the maxillary first molar (U6) to the palatal plane (PP)); (6) U1 to palatal plane distance (the perpendicular distance from the tip of the maxillary central incisor (U1) to the palatal plane (PP)); (7) L6 to mandibular plane distance (the perpendicular distance from the mesial cusp tip of the lower first molar (L6) to the mandibular plane (MP), also known as the mandibular plane); (8) L1 to mandibular plane distance (a linear cephalometric measurement in orthodontics that quantifies the distance from the incisal edge of the mandibular central incisor (L1) to the mandibular plane).

Figure 3.7: Cephalometric analysis: i. Overbite; mm; ii. U6 (Upper 1st molar) to palatal plane distance, mm; iii. U1 (Upper central incisor) to palatal plane distance, mm; iv. L6 (Lower 1st molar) to mandibular plane distance, mm; v. L1 (Lower central incisor) to mandibular plane distance, mm; vi. L1 (Lower central incisor) to mandibular plane angle (IMPA); vii. U1 (Upper central incisor) to palatal plane angle; viii. Interincisal angle.

The amount of molar intrusion will be measured following these steps (Figure 3.8) Withayanukonkij et al. (60):

1. Palatal plane (PP) will set,
2. The deepest point of the central pit (C-pit) will be in the coronal and sagittal view, and
3. The vertical distance from C-pit to PP (U6-PP) will be measured. The difference between T0 and T1 will be the intrusion amount, and the right and left sides will be averaged.

Figure 3.8: Show maxillary molar measurement. C-pit indicates central pit of maxillary molar; PP. palatal plane; U6-PP, vertical distance from C-pit to PP.

2. Patient-reported outcomes measures (PROMs) (appendix 1) Participants will complete a set of Patient-Reported Outcome Measures (PROMs). Initially, participants will be required to provide several pieces of information, including name, date of birth, gender, residential address, phone number, email address, and date of consultation. Subsequently, participants from all three study groups will respond to ten PROM items assessing various aspects of outcome measures: "I feel pain", "I can move more easily", "I feel strong", "I feel coordinated", "I feel tired", "I can sleep", "I can do activities of daily living", "I can return to work and sports", "I am satisfied with my care", and "I would recommend physical therapy to others". Each item will be rated using a 5-point Likert scale, with response options ranging from 1 (strongly disagree) to 5 (strongly agree) (Figure 8). All personal and response data will be treated with strict confidentiality. This interview questioner will take before and after the treatment.

Inclusion Criteria:

1. Age 18-35 years,
2. Both genders.
3. The patient is well fitted with no systemic disease.
4. Mild-moderate dental anterior open bite.
5. Well-aligned or mildly crowded dentition.

Exclusion Criteria:

1. Patient with a history of trauma to the molars or incisors.
2. Patient with a history of endodontic treatment to the maxillary first molar or incisors.
3. Patient with a systemic disease related to bone metabolism.
4. Patient taking immunosuppressive drugs or drugs inhibiting or accelerating tooth movement; and
5. Patient with neuromuscular deficiencies.

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.