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The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author. Author Contributions

The authors would like to thank Daniel Seiler, Laboratory Manager Medical Additive Manufacturing at the University of Applied Sciences Northwestern Switzerland FHNW, Muttenz, for his invaluable support in providing the 3D printed titanium prototypes. Abbreviations Zafar, M.S. Prosthodontic Applications of Polymethyl Methacrylate (PMMA): An Update. Polymers 2020, 12, 2299. [ Google Scholar] [ CrossRef] [ PubMed] Oliveira, A.M.P.; Amorim, R.L.O.; Brasil, S.; Gattás, G.S.; de Andrade, A.F.; Junior, F.M.P.; Bor-Seng-Shu, E.; Iaccarino, C.; Teixeira, M.J.; Paiva, W.S. Improvement in neurological outcome and brain hemodynamics after late cranioplasty. Acta Neurochir. 2021, 163, 2931–2939. [ Google Scholar] [ CrossRef] Wu, C.T.; Yang, Y.H.; Chang, Y.Z. Three-Dimensional Deep Learning to Automatically Generate Cranial Implant Geometry. Sci. Rep. 2022, 12, 1–10. [ Google Scholar] [ CrossRef] Citation: Egger J, Gall M, Tax A, Ücal M, Zefferer U, Li X, et al. (2017) Interactive reconstructions of cranial 3D implants under MeVisLab as an alternative to commercial planning software. PLoS ONE 12(3):

Egger J, Tokuda J, Chauvin L, Freisleben B, Nimsky C, Kapur T, et al. Integration of the OpenIGTLink network protocol for image-guided therapy with the medical platform MeVisLab. Int J Med Robot. 2012; 8(3): 282–90. pmid:22374845 Li X, Yin Z, Wei L, Wan S, Yu W, Li M. Symmetry and template guided completion of damaged skulls. Computers and Graphics 2011; 35(4): 885–893.

In this section, the proposed methodology for designing and fabricating a biomimetic, lightweight patient-specific cranial prosthesis is described. The overall workflow was performed in three modules, as described in detail below. Preoperative Medical Image Data Acquisition and Processing Meglioli, M.; Naveau, A.; Macaluso, G.M.; Orsi, M.; Barone, M.; Cucchi, A.; Cossellu, G.; Marchetti, C.; Masotto, N.; Panciera, A.; et al. 3D printed bone models in oral and cranio-maxillofacial surgery: A systematic review. 3D Print. Med. 2020, 6, 30. [ Google Scholar] [ CrossRef] Sprio S, Fricia M, Maddalena GF, Nataloni A, Tampieri A. Osteointegration in cranial bone reconstruction: a goal to achieve. J Appl Biomater Funct Mater. 2016; 14(4):e470–e476. pmid:27311430 Jegadeesan, J.T.; Baldia, M.; Basu, B. Next-Generation Personalized Cranioplasty Treatment. Acta Biomater. 2022, 154, 63–82. [ Google Scholar] [ CrossRef] [ PubMed]Li X, Xu L, Zhu Y, Egger J, Chen X. A semi-automatic implant design method for cranial defect restoration. Int J CARS 11 2016; (Suppl 1): S241–S243. Neha Sharma 1,2 † Daniel Ostas 3 † Horatiu Rotar 3 Philipp Brantner 2,4 Florian Markus Thieringer 1,2 * Winkler, P.A.; Stummer, W.; Linke, R.; Krishnan, K.G.; Tatsch, K. The influence of cranioplasty on postural blood flow regulation, cerebrovascular reserve capacity, and cerebral glucose metabolism. Neurosurg. Focus 2000, 8, 1–9. [ Google Scholar] [ CrossRef]

Marreiros FM, Heuzé Y, Verius M, Unterhofer C, Freysinger W, Recheis W. Custom implant design for large cranial defects. Int J Comput Assist Radiol Surg. 2016; 11(12): 2217–2230. pmid:27358081

In the case of the skull of U. spelaeus ladinicus, it was acquired with a XμCT system (see Table 1 and Supplementary Data). The virtual reconstruction of U. spelaeus ladinicus is shown in Figure 8. In this case, only the right temporomandibular joint (TMJ) and the left canine were virtually repaired in Mimics. For repairing the right TMJ, a preliminary step was performed to preselect the left TMJ. With this anatomical selection, we proceeded to mirror the structure (the command is CMF/Simulation→Mirror in Mimics) ( Figures 8A–D). As this structure is essentially formed by trabecular bone with a high complexity of the trabeculae, it is unfeasible to generate a new layer of bone as performed in other fossils. Therefore, the easiest way to proceed here was to adapt the repositioned fragment and merge it later, through the command CMF/Simulation→Reposition and Merge in Mimics ( Figures 9A–D). The left canine was precisely reconstructed in the alveolar cavity, adapting the shape, size, and orientation of such dental piece to the specific anatomical requirements with the same command reposition tool ( Figure 9B). With this process, the skull of U. spelaeus ladinicus is fully repaired and reconstructed with the TMJ and the left canine ( Figure 9C). Once the skull was virtually reconstructed, its mesh was postprocessed. The analysis is explained in detail in “Mesh Postprocessing” section. Conclusion Piitulainen, J.M.; Kauko, T.; Aitasalo, K.M.; Vuorinen, V.; Vallittu, P.K.; Posti, J.P. Outcomes of Cranioplasty with Synthetic Materials and Autologous Bone Grafts. World Neurosurg. 2015, 83, 708–714. [ Google Scholar] [ CrossRef] [ PubMed]