## 2 Materials and Methods  
The current study was based on a retrospective multi centric analysis of patients who underwent mandibular reconstruction, benefiting from the application of a plate produced with computer-aided manufactory (CAD-CAM) technology, and for whom a bone free flap was contraindicated. The patients were treated at the Maxillofacial Surgery Unit of Policlinico S. Orsola of Bologna, Italy, and Policlinico San Marco, Catania, Italy, from April 2016 to June 2021. The study was approved by the S. Orsola Hospital Ethics Committee (approval no. 57/2011/O/Disp). The inclusion criteria were:  
- Age \(\geq\)18 years;  
- Osteonecrosis of the mandible induced by biphosphonates;  
- Clinical and radiological signs of mandibular involvement under the course of the mandibular canal;  
- Contraindications to the use of reconstruction with bone-free flap transfer;  
- Need of primary or secondary reconstruction of mandibular continuity defects;  
- Reconstruction with customized mandibular bridging plate with or without flee flap transfer. The exclusion criteria were:  
- Reconstruction with a standard osteosynthesis plate, with or without bone-free flaps;  
- Osteoradionecrosis of the jaw. All surgical and reconstructive procedures were virtually planned and performed according to our CAD-CAM protocol. All patients underwent a CT scan examination and the images obtained were saved in DICOM (Digital Imaging and Communication in Medicine) format. Using the Mimics (Materialize) software, the images were segmented, and the bone tissue was isolated from the soft tissues. Segmented images made it possible to reconstruct the 3D model of each patient's bone tissue (Figure 1). The STL files of the models obtained in the previous phase were imported into the 3-Matic (Materialize) design software. In the design of the device, the morphology of the bone defect, after the virtual resection, was recreated thanks to the superimposition of the healthy area, mirrored with respect to the sagittal plane (Figure 2). Figure 1: 3D model of the patient. Figure 2: Virtual resection planning. The fixing system was created by designing anatomical plates which, by means of screws, ensure the stability of the implant. The preoperative planned resection was transferred into surgery using anatomical cutting guides. The unique positioning of the cutting guides ensures the execution of cuts with the orientation and position defined by the surgeon during the virtual simulation (Figure 3). Once the design phase was completed, the files were saved in STL format and processed to be produced using EBM (electron beam melting) additive technology from titanium alloy powder (Ti6 Al4V-ELI). After surgery, all patients underwent a control CT examination, and with the same procedure, the 3D models of bone and implant were obtained. To assess the accuracy between preoperative planning and surgery, the models obtained were imported into the design environment. The \"Create Part Comparison Analyzes\" function of the Analyze window of the 3-Matic software allowed us to compare the 3D design models with the 3D reconstructions obtained from the postoperative CT images. The result of the analysis is a deviation in millimeters between the nodes of the triangles of the two models. This result can then be displayed on the 3D models thanks to a color scale or a histogram, which provides the number of points for each deviation value at a given slider thresholds value (Figure 4). The surgical procedure was carried out, avoiding intra-oral access when possible. Through a cervicotomy access, the cutting guides were positioned and osteotomies performed as pre-operatively planned, using a piezoelectrical bone saw (Piezonsurgery Medical, Mectron, Genoa, Italy). Then, the customized reconstructive plate was positioned to restore the mandibular anatomy, and fixed with 2.0 screws (Figure 5). When, necessary, the end oral defect was reconstructed with a soft tissue free flap transfer.