# 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
Figure 4: SEM/EDS analysis of Sr-HA scaffold material before (**a**) and after the ionic exchange with Mg (**b**). The appearance of Mg and Cl signals is evident in (**b**). for hydroxide [42; 43]. Chloride substitution, however, does not represent a problem for biomaterial applications, because Cl is physiologically present in biological systems, and it actually enhances the osteoconductivity of synthetic hydroxyapatite [43]. The XRD results were supported by EDS analysis on Sr-HA before and after Mg ion exchange. This analysis confirmed the trends in the elemental contents and molar ratios (Table 2) and highlighted that the ion exchange was already effective with 1M Mg for 1 day. In addition, the data suggest that a preferential substitution of Sr ions is likely to have occurred first, followed by Ca ions exchange at a later stage, when exposure was extended to 5 days. \begin{table}
\begin{tabular}{l c c c c c c c c c} \hline  & **Ca** & **P** & **Mg** & **Sr** & **Ca/P** & **Mg/Ca** & **Sr/Ca** & **Mg/Sr** \\  & **(mol\%)** & **(mol\%)** & **(mol\%)** & **(mol\%)** & **Ca/P** & **(cad/P)** & **Mg/Ca** & **Sr/Ca** & **Mg/Sr** \\ \hline SrHA & 21.87 & 14.45 & - & 2.84 & 1.51 & 1.71 & - & 0.130 & - \\ SM1d1 & 21.83 & 13.80 & 0.74 & 2.64 & 1.58 & 1.83 & 0.034 & 0.121 & 0.280 \\ SM1d5 & 21.03 & 13.90 & 1.00 & 2.69 & 1.51 & 1.78 & 0.048 & 0.128 & 0.372 \\ SM2d1 & 22.00 & 13.52 & 0.89 & 2.59 & 1.63 & 1.88 & 0.040 & 0.118 & 0.344 \\ SM2d5 & 20.46 & 13.53 & 1.79 & 2.57 & 1.51 & 1.83 & 0.087 & 0.126 & 0.696 \\ \hline \end{tabular}
\end{table} 
Table 2: Element contents (mean values of three measurements) and molar ratios of the sintered porous Sr-HA samples after performing the Mg ion exchange treatment using Mg solutions 1M and 2M for 1 and 5 days each. Figure 5: Maps of elements detected by SEM-EDS analysis in scaffold material after the ionic exchange with Mg. The detected elements are all uniformly distributed in the analyzed area, with points’ density qualitatively reflecting their relative contents. ICP-OES analysis confirmed that the ion exchange solutions were enriched in Sr and Ca and depleted in Mg but, due to high initial Mg concentrations, the data are strongly affected by dilution and/or instrumental errors, which limited the reproducibility and reliability of the obtained values. The selected conditions, however, allowed the synthetic apatite lattice to retain higher Sr concentrations than those in bone. This could be clinically beneficial since it can be envisaged that Sr ions can be released from the scaffold into the surgical receiving site and thus exert a localized therapeutic activity, possibly reducing the need for oral administration. As for Mg, substitutions were obtained close to and beyond the maximum biological levels in hard tissues. In particular, the Mg weight content in the material after immersion in 1 M-Mg solution for 1 day was around 1.1 wt%, i.e., close to its maximum biological value. More severe ion exchange conditions (2 M for 5 days) seemed to strongly alter the material. The Mg/Ca ratio reached about 9%, which means that the maximum possible ion exchange with Mg for Ca in the lattice was obtained and the amount of Mg exceeding that value was likely localized in the hydrated surface layer of the material [28]. The crystallographic cell volume of the material was actually quite similar among the samples after 5 days of ion exchange, regardless of Mg concentrations. However, since the stronger conditions of ion-exchange treatment were not necessary to the purpose of our study, they were disregarded for further investigations. Both the Sr-HA architectures (sponge replica and foams) were successfully converted into MgSr-HA by ion exchange. Mg incorporation in the cationic crystallographic sites was, therefore, possible and could be adjusted by ion exchange on porous sintered Sr-HA, independently of the process used for material shaping. This feature is particularly appealing if developments in scaffold production technology, including rapid prototyping [4], are considered.