# Mg,Sr-Cosubstituted Hydroxapatite with Improved Structural Properties
## 3 Results and Discussion
### Ion Exchange of Mg in Sr-HA Samples: \"Subsequent Mg Substitution\"
#### 3.2.2 Effectiveness of the Process  
To test ion exchange, porous sintered Sr-HA scaffolds produced by either sponge impregnation (a, b, c) or by direct foaming (d, e, f) were used (Figure 2). Both scaffold types presented ultra-macropores up to millimetric scale (Figure 2a,d), which were highly interconnected through windows on the pore walls of size from hundreds to tens of microns down to micron (Figure 2b,c,e,f). These architectures are known to perform well both in vitro and in vivo because they allow for physiological fluid permeation and cell colonization [37; 38; 39]. The porous samples of Sr-HA sintered at 1250 \({}^{\circ}\)C showed no secondary phases besides apatite before and after Mg ion exchange (Figure 3a,b). The elements detected by EDS (Figure 4a,b); therefore, all belonged to the apatite lattice in both cases. The effectiveness of Mg ion exchange in Sr-HA can be explained on the basis of the opposite size of Mg and Sr ions, as compared with Ca ion size [27]: the bigger size of Sr\({}^{2+}\) (1.12 A) compensates for the smaller size of Mg\({}^{2+}\) (0.89 A), as compared to Ca\({}^{2+}\) (0.99 A), and thus, it stabilizes the cosubstituted MgSr-HA lattice. However, the presence of two Ca sites in the HA lattice makes it difficult to evaluate the extent of single substitutions on the basis of the crystallographic cell modification, which is, however, useful to gauge the overall influence of coexisting substituting ions. It has been reported that Mg substitutions decrease the a and c parameter values of the HA lattice, while Sr substitutions increase a and c parameter values [27; 28; 37; 40]. Figure 3: XRD spectra of the sintered porous Sr-HA before (**a**) and after the Mg ion exchange (**b**). Figure 2: SEM images of the porous sintered scaffolds prepared by sponge impregnation method (**a**–**c**) and direct foaming (**d**–**f**) showing the multiscale pores affecting the constructs. Although cell parameters, when taken singularly, may not be accurate, we observed a reproducible trend of volume reduction for the crystallographic cells of our scaffolds, indicating the exchange of some lattice cations with Mg ions (Table 1). A higher decrease in cell volume was observed with solutions containing higher Mg concentrations or with longer immersion. Time is a critical factor since similar crystallographic cell volumes can be obtained using different Mg concentrations, once the immersion duration is set. The EDS analysis of numerous cross sections of the scaffold revealed a homogeneous composition and demonstrated that the Mg ion exchange process involved the whole sample and was not limited to its surface or localized areas. Figure 5 shows an example of the mapping of each element detected by EDS in the examined area (green colored in the upper image). The density of points reflects the relative amounts of the detected elements. Noteworthy, Cl also may have been incorporated into the HA lattice since EDS (Figure 5) detected Cl quite homogeneously distributed in the sample, and no evidence of Mg chloride was observed by XRD analysis (Figure 3b). The changes in cell parameters due to Mg entrance in the HA lattice could therefore be partially hidden by the incorporation of Cl ions, which expanded the cell volume: a significant increase of a and c axis parameters was observed in Cl- apatites, as compared to HA, due to the presence of bigger Cl ions (1.81A) substituting for OH groups (1.68A) [41]. Other studies reported that a and c, respectively, increased or decreased together with the amount of chloride substituting \begin{table}
\begin{tabular}{c c c c} \hline \hline  & **a (Å)** & **c (Å)** & **V (Å3)** \\ \hline SrHA & 9.462 & 6.913 & 536.0 \\ SM1d1 & 9.418 & 6.880 & 528.4 \\ SM1d5 & 9.342 & 6.827 & 516.0 \\ SM2d1 & 9.407 & 6.879 & 527.2 \\ SM2d5 & 9.352 & 6.819 & 516.5 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Lattice parameters and cell volume of the material before and after the ionic exchange tests.