## 4 Discussion
This kind of phantom can reduce the effects of many error sources, such as change in acquisition settings, resolution, or those due to the scanner itself. It is also important to consider that voxel density values are less stable for CBCT equipment than MSCT, with noticeable variations even within the same scan for materials with homogeneous composition [50]. For these reasons, the quantitative method used in this study was limited to the assessments of compact bone volume, after appropriate segmentation, without further investigations about bone densities and composition. The determination of the threshold used for the extraction of bone volumes was not particularly critical given the high degree of separation with respect to the soft tissue densities, for all the considered equipment [49; 50]. The developed novel radiological approach not only was successfully tested in a set of different cases related to different anatomical districts confirming its robustness but also allowed drawing conclusions on SB performances. In each analyzed case, good results were recorded: The geometry of the volumetric increase was similar or identical to the lack of bone in the injured area, and, importantly, the amount was expected, considering both post-surgery timing and defect shape. Independent experienced users judged the overlapping of the images to define the acceptable score: This explains minor displacements differences, by a few millimeters, between first and second alignment. As expected, the volumetric increase was not the same in all patients because of both different investigated anatomical sites and different post-surgery times. Additionally, bone resorption also differed among patient as it depends on age and on other possible pathologies as well as on the size of the region where SB was grafted. Thus, although it was not possible to estimate the growth of SB at a given time, the results showed that this scaffold allowed the formation of new bone in all the examined cases, coherent with literature evidences. We also demonstrated a volumetric increase in each patient. Moreover, there is a clear morphological pattern on the evolution of the standard X-Ray imaging series over time which shows the substitution of the grafted material with a more homogeneous signal in the area of graft implant. The progressive remodeling together with an increase of the mineral signal cannot be dependent on the active remodeling of the graft _per se_ given it is a decellularized matrix. Therefore, the increase in the density over time must be dependent on novel mineral matrix exposition likely induced by the graft as previously shown in vitro [30]. This neo-deposition is quantified in the measures reported using CT scan. Indeed, clinically, partial increase of bone regeneration was already evident from CT scans performed 6 to 7 months post-surgery, likely due to the regeneration process ongoing, while obtained bone gain allows obtaining complete anatomy in a two-years timeframe averagely. Furthermore, bone growth was not only limited to the site where SB was inserted, but new bone was also growing in the areas adjoining the implant, suggesting that bone growth continued until the natural anatomy of the site was fully restored, further confirming SB mechanism of action.