## 4 Discussion

Table 3: Differences (\(P\)-values) of adhesion between Group 3 (PE: pre-eclampsia) vs. Groups 1 (<40) and 2 (>40). osteoblastic differentiation on microscale titanium substrates [46]. Slight but significant variations in \(\alpha\)3, \(\alpha\)4 subunits, and \(\alpha\)V expression, as well as \(\beta\)1 and \(\beta\)5 subunits have been observed in the interaction of nanostructured titanium surfaces and MSCs, when studied in terms of focal adhesion and differentiation [47]. Thus, the expression of integrins may condition the spreading and adhesion of MSCs onto titanium surfaces and be in turn affected by attachment to the titanium. Our data strongly indicate that CD29 is implied in adhesion to titanium disks, since PE hAMSCs showed a reduction in both its expression and adhesion, while these features were not affected in hAMSCs obtained from non-aged and aged donors. On the other hand, our data also showed that CD73 (ecto-5\({}^{\prime}\)-nucleotidase) was decreased in hAMSCs obtained from aged and PE women. CD73 has been implicated in cell-cell and cell-matrix interactions [48]. However, hAMSCs obtained from aged women did not display a reduction in adhesion to titanium, suggesting that CD73 is not essential for, or contributes at a lower extent, to the adhesion of these cells to titanium. Nevertheless, an interesting relationship between CD29 and CD73 in MSCs has been found. [PERSON] et al. [49] have demonstrated that a mechanical loading of MSCs embedded in fibrin led to a reduced surface expression of CD73 and CD29, but not of CD105, and also to a decrease in the migratory response after loading, possibly via FAK/Src family kinase signaling. Despite the fact that CD29 and CD73 seem to be independently regulated by mechanical loading, nevertheless these results are interesting for a better understanding of the interaction of MSCs with the matrix, and thus their role should be further investigated in the context of adhesion to titanium implants. Titanium surfaces are increasingly used as the substrate for improving adhesion, osseointegration, and host response in terms of avoiding bacterial contamination [27; 50]. Surface roughness has been demonstrated to be an essential parameter to promote osteoblastic differentiation and maturation of MSCs in dental implants made by titanium [4]. In particular, enhanced differentiation and maturation of MSCs towards the osteoblast lineage was shown on sandblasted rough surfaces as compared with smooth surfaces [51; 52; 53]. The canonical Wnt signaling is involved in early osteoblast differentiation, Ca2\({}^{+}\)-dependent Wnt5a signaling, as well as Dkk2, BMPs, and integrins, regulates osteoblast differentiation of MSCs on hydrophilic surfaces with hierarchical roughness [4; 51]. However, hAMSCs obtained from non-aged and nonpathological pregnancies adhered, survived (and likely initiated to proliferate) similarly on smooth and sandblasted disks. This might be due to the microroughness or other properties of titanium surfaces used in this study, which should be optimized. It has been prospected that increased bone response is obtained when surfaces are modified for their microtopography, surface chemistry, hydrophilicity, and nanoroughness [54]. All in all, our data point out that hAMSCs obtained from aged women can have lower differentiative capacities, but they adhere to the substrate used in osteoinduction and osseointegration as cells from non-aged donors do. On the other hand, PE hAMSCs are not only obtainable with low yield, but also adhere less onto titanium surfaces.