# Mg,Sr-Cosubstituted Hydroxapatite with Improved Structural Properties
## 3 Results and Discussion  
### Thermal Stability of As-Prepared Mg,Sr-Cosubstituted HA  
We previously showed that strontium cosubstitution stabilizes synthetic Mg-substituted HA in thermally untreated, as-prepared materials (apMgSr-HA) [28].  
Chemophysical and in vitro tests suggested that porous macro-granules of apMgSr-HA could be used as resorbable fillers for bone defects, because these granules could release Sr and Mg ions for a longer time than the corresponding Sr-free compositions, a potential benefit for new bone formation.  
High temperatures, however, degrade the apatite phase of apMgSr-HA, because of the presence of Mg, although apMgSr-HA is actually less sensitive to heat than Sr-free Mg-substituted HA, where secondary phases may form already around 400 \({}^{\circ}\)C [34,35].  
TGA (Figure 1A) and XRD (Figure 1B-D) analyses of apMgSr-HA revealed that increasing the Mg/Ca ratio in the adopted synthesis from 0.15 to 0.25 enhanced the thermal instability of the material. In particular, TGA and the related DTG curves showed a bigger and earlier weight loss for the apMgSr-HA powder derived from Mg/Ca reactant ratio of 0.25, compared to 0.15.  
XRD spectra showed no secondary phases in the synthetic apMgSr-HA after heating at 600 \({}^{\circ}\)C, regardless of Mg concentration (Figure 1B). Secondary phases were also not observed in synthetic apMgSr-HA materials prepared with a Mg/Ca synthesis ratio of 0.15 and 0.20, after heating at 800 \({}^{\circ}\)C (Figure 1C), while 10-20 vol% of \(\beta\)-TCP was estimated to form after calcination at 1000 \({}^{\circ}\)C (Figure 1D). The apatite cell parameter values increased with the treatment temperature, and this trend was associated with Mg depletion.  
When the starting Mg/Ca ratio was increased to 0.25, 10-15 vol% of \(\beta\)-TCP formed at just 800 \({}^{\circ}\)C (Figure 1C). The secondary phase increased up to 40-45 vol% when the material was fired at 1000 \({}^{\circ}\)C (Figure 1D). This higher apatite instability obtained by increasing the Mg/Ca ratio of the adopted synthesis from 0.15 to 0.25 is associated with the increase in Mg content in the powder from 1.5 wt% to 3.0 wt%. These values correspond to Mg/Ca ratios of  
Figure 1: (**A**) TG (continue line) and DTG (point and line) curves of the synthetic powders prepared with synthesis molar ratios Sr/Ca = 0.20 and Mg/Ca = 0.15 (black curve) and 0.25 (red curve); (**B–D**) XRD spectra of the synthetic MgSr-HA granulate prepared with synthesis molar ratios Sr/Ca = 0.20 and Mg/Ca = 0.15 (a), 0.20 (b) and 0.25 (c) after thermal treatment at 600 \({}^{\circ}\)C (**B**), 800 \({}^{\circ}\)C (**C**), 1000 \({}^{\circ}\)C (**D**). The references to HA ICDD card n.09-0432 and \(\beta\)-TCP ICDD card n.09-0169 are indicated; * shows the signal of the main peak of \(\beta\)-TCP.  
about 6 mol% and 12 mol%, respectively, which suggests a limited yield for ion substitution. Noteworthy, 12 mol% is beyond the maximum possible limit of substitution, which is about 9 mol%; as a consequence, the Mg in excess did not enter the HA crystallographic cell but was confined to the amorphous surface layer [28].  
It could be speculated that these MgSr-HA macro-granules could be clinically used as fillers in bone defects, e.g., after surgery or trauma, and additional thermal treatments (<1000 \({}^{\circ}\)C) could be applied to decrease the ion release rate of the material and thus prolong its release because firing reduces material reactivity. However, the lack of morphological and structural 3D organization in a granulate biodevice may limit its use, especially when clinical conditions require a bioactive 3D porous scaffold, with suitable biomechanic features. To compound the problem further, such mechanical properties could be indeed achieved by high-temperature sintering (1250 \({}^{\circ}\)C), but this would degrade cosubstituted apSr,Mg-HA into secondary phases.  
Therefore, an alternative strategy had to be devised to obtain sintered porous architectures made of Mg,Sr cosubstituted HA with adequate structural properties.