## 2 Materials and Methods  
The study protocol was reviewed, approved, and registered with the number 5900R by the Ethics Committee of the Medical Faculty of Heinrich Heine University, Dusseldorf. The investigations were performed on 6 human ex vivo frozen specimens from adult donors provided by the Center for Anatomy II (University Hospital Dusseldorf), presenting teeth in the premolar and molar region and intact oral tissues. For each specimen, an initial CBCT image (Orthophos SL 3D CBCT from Dentsply Sirona Inc., York, PA, USA) was taken (T0) and, subsequently, silicone impressions (Provil novo, fast set, Kulzer GmbH, Hanau, Germany) were taken of the maxilla to obtain plaster models. These were digitized using an optical laser scanner (orthoX(r) scan 3D model scanner, Dentaurum GmbH and Co. KG, Ispringen, Germany) by means of a software program (orthoX(r) scan). For each sample, a T-shaped area (T-zone) posterior to the third pair of palatal folds was selected for inserting 10 orthodontic mini-implants (9 mm length \(\times\) 2 mm diameter; BENEfit(r), PSM Medical, Gunningen, Germany) with the same insertion axis using two different custom-made insertion guides (Figure 1). Thirty mini-implants were placed using full-arch guides (from Easy Driver, Uniontech, Parma, Italy) (Figure 2a), and thirty using skeletonized templates fabricated in-house using Blender software (Blender Foundation, Amsterdam, The Netherlands) and an SLA-printer (Form 3, Formlabs Inc., Berlin, Germany) (Figure 2b). The groups were randomized according to the different regions of the palates, and half of the mini-implants were inserted using a pre-drilling procedure, while the other half were inserted without. For each maxilla, the implants were randomized using a true random number generator (random.org, Dublin, Ireland) as follows: (1) randomization  
Figure 1: Insertion scheme of the 10 mini-implants in the T-zone. Figure 2: (**a**) Full-arch insertion template in which the entire oral mucosa as well as the occlusal surface of the maxillary teeth is covered; (**b**) skeletonized insertion guide, supported by selected teeth in premolar and molar region and leaving the oral palatal mucosa visible. of the palatal side on which the mini-implants were inserted with pre-drilling or without pre-drilling (split-mouth design); (2) randomization of the four median mini-implants in pre-drilling group and non-pre-drilling group; (3) randomization of the 60 mini-implant in the two different insertion guides group (i.e., full-arch or skeletonized). The Surgic Pro + motor was used both for pre-drilling and mini-implant insertion, with the following settings: 40 rpm speed and 30 Ncm insertion torque. In the pre-drilling group, a 1.4 mm pre-drill was used. Further details on the allocation process are provided in Figure 3.  
After mini-implant insertion, another CBCT of the sample was taken using the Orthophos SL 3D CBCT (Dentsply Sirona Inc.) (T1) and then superimposed to the initial one using Amira (Amira R 6.4.0 Thermo Fisher Scientific, Waltham, MA, USA). The CBCTs were acquired using the high-definition mode. Further details on the acquisition parameters are provided in Table 1.  
Maxillary bone segmentation was performed in Amira (Amira R 6.4.0, Thermo Fisher Scientific) using the following threshold settings: 240 (preoperative and postoperative CBCTs); while for mini-implant segmentation, the threshold was set to 1500. The postoperative scans and the original plannings contained in the pre-operative scans were superimposed using rigid registration. To measure the deviation between the planned and the actually achieved position of the mini-implants, the respective transformation matrices were obtained. The coordinates of the implant neck and apex were copied, and using MATLAB software (MathWorks, Portola Valley, CA, USA), the distances at the respective positions were calculated.