## 3 Results
The results deriving from this analysis are listed in Table 1 and described below. Figure 1: Phase-contrast MicroCT 3D images of representative samples. (**a**) Collagen membranes (COL) scaffold before grafting; (**b,c**) repaired cavarial defects: (**b**) representative sample of the COL group; (**c**) representative sample of the COL/hPDLSCs/PEI-EVs group; (**d**) poly-(lactide) scaffold (PLA) scaffold before grafting; (**e,f**) repaired cavarial defects: (**e**) representative sample of the PLA group; (**f**) representative sample of the PLA/hGMSCs/PEI-EVs group. Red arrows indicate the defect site in each panel. Phase-contrast signal (grey cloud of points) close to the defects repaired using PLA-based constructs represents PLA residuals. Figure 2: Parameters of interest for the analysis of bone relative mass density distribution (MDD\({}^{\prime}\)). **(a)** Histogram of a representative sample: the peak on the right, highlighted in translucent blue, was referred to the overall mineralized bone that was regenerated into the defect. The parameters investigated with the Roschger approach are indicated. **(b–d)** Study of the sensitivity of the Roschger approach: box plots of the distribution (**b**) of the mean relative mass density (MDD\({}^{\prime}\)mean) and (**c**) of the full width at half maxima of the distribution (MDD\({}^{\prime}\)fwhm) in the whole set of _ctr_ sites (i.e., in the calvaria but outside the defect); **(d)** dispersion graphs describing mean vs. fwhm dependency, the two regression equations and their coefficient of determination R\({}^{2}\) for the full sets of ctr and test data. Samples COL and PLA: the sole use of the biomaterial, regardless of its nature (COL or PLA), does not support complete regeneration either from a morphometric (volumetric) point of view, as previously observed [16; 17; 18; 19; 20], or from a comparison of the mineralization density distribution of test sites vs. control sites. Indeed, regenerated sites (test) in both the constructs presented positive values of \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm i}\) for all the \(i\) variables (peak, mean, fwhm, low and high), indicating lower levels of mineralization than in \(ctr\) sites. Samples COL/hPDLSCs and PLA/hGMSCs: the combination of biomaterials with the related stem cells has significantly improved the level of mineralization of the constructs. In any case, limited to the use of hPDLSCs, mineralization density distributions are still found shifted towards lower levels than in \(ctr\) sites, as suggested by the positive \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm fwhm}\) combined to the negative \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm low}\). Samples COL/hPDLSCs/CM and PLA/hGMSCs/CM: the addition of the CM to the constructs, in the COL/hPDLSCs/CM samples, seemed to furtherly increase overlapping with the control sites, whereas in the case of PLA/hGMSCs/CM samples, they seemed to reach even higher levels of mineralization than the controls, with higher mean and variability values (negative \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm mean}\) and negative \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm fwhm}\), respectively) than control sites in the same calvariae. Samples COL/hPDLSCs/EVs and PLA/hGMSCs/EVs: the substitution of the CM with the EVs did not seem to modify the mineralization distribution in the COL/hPDLSCs/EVs samples. Conversely, it appeared to be a less contributory choice in terms of mineralization in the case of use of PLA/hGMSCs/EVs constructs, where higher mean, low and high values (i.e., positive \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm mean}\), \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm low}\) and \(\Delta\)MDD\({}^{\prime}\)\({}_{\rm high}\) ) were found in the control sites than in the test sites of the same calvariae.