## Materials and Methods
### Anatomical and Technical Model Generation  
The geometrical model that is subject to the finite-element studies is shown in Figure 1b and was built up from the results of two modelling steps: firstly the anatomical modelling, i.e., creating the model of the defective minipig mandible and its surrounding tissue; secondly, the technical modelling, where technical components such as the electro-stimulating implant or osteosynthesis plates and screws are created. The anatomical modelling of the regarded model object, i.e., the minipig mandible, was done based on CT data of a 17-month-old male Gottingen minipig, see Figure 1a. The CT data comprised 442 slices with 512 \(\times\) 512 pixels each and a pixel spacing of ca. 0.39 mm. The slice thickness was 1 mm and the spacing between the slices was 0.5 mm. By segmenting the data, i.e., assigning certain thresholds of gray values to the respective biological tissue (cortical bone, teeth, and soft tissue) a first rough anatomical model was created. For this, we used the image processing software Materialise Mimics(r) version 19 (Materialise, Leuven, Belgium. [[http://www.materialise.com](http://www.materialise.com)]([http://www.materialise.com](http://www.materialise.com))). One part of the anatomical model is the mandible (cortical bone) from which the teeth were subtracted. This was done to avoid unnecessary small details in the geometry that might lead to problems during the simulation. This is valid since the field amplitude can be easily estimated to be well below the stimulation threshold in the neighborhood of the teeth. The resulting coarse anatomical model (stereolithography (STL) file) was imported into the CAD software Materialise 3-matic(r) version 11 (Materialise, Leuven, Belgium. [[http://www.materialise.com](http://www.materialise.com)]([http://www.materialise.com](http://www.materialise.com))) to be further processed. The modifications included manually filling larger holes in the geometry object that resulted from subtracting the teeth, wrapping (i.e., automatically filling smaller holes and creating a \"watertight\" model), smoothing of the surface, and removing other geometrical artefacts such as spikes, double or intersecting triangles, and sharp triangles. The latter modifications were performed automatically using 3-matic's \"Fix Wizard\". In addition, manually performed local smoothing of the surface ensured removal of further unwanted and unrealistic geometric features (little bumps and unevenness of the surface). Finally, the number of triangles describing the STL object were reduced, while preserving the mesh quality. The soft tissue domain was created analogously: Firstly, the coarse STL file resulting after segmentation was imported into Materialise 3-matic(r) and the ears and the upper part of the minipig head were removed. Again, here the fields can be assessed to be negligible with respect to the stimulation threshold. Secondly, wrapping, smoothing, and repairing analogously to the bone geometry was performed. To create a skin domain, the _hollow_ operation was used to create a shell  
Figure 1: (**a**) Computer tomographic pictures of the head of a minipig. To reduce unnecessary computational costs in the later simulations the upper part of the head has been removed in the modelling process. (**b**) CAD model of a defective minipig mandible and its surrounding tissues, equipped with an electro-stimulating implant. The critical size defect (region of interest) is highlighted in red. (**c**) Bipolar electro-stimulating implant consisting of stimulating electrode (“Electrode 1”), insulator and counter-electrode (“Electrode 2”). The parameters \(h_{\text{el}}\) and \(q_{\text{stim}}\) are to be optimized. with a uniform thickness of 2.28 mm [49]. Soft tissue and skin object were uniformly remeshed with a desired edge length of 3 mm. After importing the bone geometry, all domains, i.e., bone, soft tissue, and skin, were then combined into one final model object by creating a non-manifold assembly.