Magnesium incorporation into β‐TCP reduced itsin vivoresorption by decreasing parathormone production

Abstract

Beta-tricalcium phosphate (β-TCP), one of the most widely used bioresorbable materials for bone therapy, can be doped with magnesium ions, generating β-TCMP. The objectives of this work were to evaluate, on a murine dental alveolus grafting model, the biocompatibility of β-TCP and β-TMCP granules by histomorphometric analysis, as well as the impact on plasmatic levels of receptor activator of nuclear factor κB ligand (RANK-L), osteoprotegerin (OPG), osteocalcin, osteopontin, and parathormone (PTH) during bone repair, using Luminex multiplexing technology. After grafting for 42 days, β-TCP grafted group presented higher bioresorption and induced more newly formed bone than β-TCMP (p < 0.05). β-TCP grafting also induced higher plasmatic levels of RANK-L, compared to β-TCMP and control (blood clot) groups at 21st day (p < 0.05). PTH, which remained at low levels in control group, presented a time-dependent increase in grafted groups, attaining significantly higher levels with β-TCP by the 42nd day (p < 0.05). RANK-L/OPG ratio increased on β-TCP group and attained a peak on the 21st day. In conclusion, β-TCP granules were more bioresorbable and osteogenic than β-TCMP granules, and the resorption of both materials might have been affected by osteoclastogenesis modulated by changes in the plasmatic levels of PTH and RANK-L.

Biological behavior of magnesium-substituted hydroxyapatite during bone repair

“…This occurs similarly with HA without Mg (Bertoni et al, 1998). The MgHA evaluated in our study showed, in the XRF analysis, a concentration of 0.47% Mg, 79% HA phase and 21% β-TCMP, and, nonetheless, the microspheres remained mostly intact at the end of the study, and did not present notorious biodegradation, in consonance with the results found by Yassuda et al (2013) and Sartori et al (2014), showing that the presence of Mg makes the ceramic biomaterials less bioresorbable, even in reduced concentrations. The microspheres implanted in GI showed a profile of biodegradation similar to GII, even without the presence of the metal.…”

“…Bone neoformation was observed, in a similar way in groups I and II, beyond the borders, in the centripetal direction, in and around the microspheres. This suggests that the incorporation of Mg into the HA structure did not favor a greater osteogenic potential to the biomaterial, corroborating with the findings of Yassuda et al (2013), which evaluated β-tricalcium phosphate (β-TCP) substituted with Mg in rats, and Sartori et al (2014) who evaluated Mg-substituted HA in sheep, both in critical bone defect. Some studies suggest that Mg inhibits the formation of amorphous CaP within the synthetic HA structure given the introduction of distorted solid structures and the structural lag resulting from inhibition of crystal growth (Bigi et al, 1992(Bigi et al, , 1993Bertoni et al, 1998;Laurencin et al, 2011).…”

Beta‐type calcium phosphates with and without magnesium: From hydrolysis of brushite powder to robocasting of periodic scaffolds

“…The reason why Mg stabilizes the structure of TCP may reside in the fact that Mg atoms are located closer to the axis of the cluster than the Ca atoms, due to their smaller ionic radius . Yassuda et al showed, in their in vivo study, that β‐TCP granules had a positive influence on osteoclast activity compared to β‐TCMP granules …”

“…Thus, for future works, the particle size and distribution should be better controlled in order to achieve a similar particle size and distribution among the groups. Beyond that, adding more water to the β‐TCMP and BCMP ink composition was necessary to adjust the ink rheology because Mg ions extend the dissolution behavior of calcium phosphates . Furthermore, the better mechanical behavior of β‐TCMP in comparison with the BCMP scaffolds could be a result of better particle packing, because the β‐TCMP powder had a multimodal distribution, whereas the BCMP powder had a unimodal one.…”

“…21 Yassuda et al showed, in their in vivo study, that b-TCP granules had a positive influence on osteoclast activity compared to b-TCMP granules. 22 The 3D structures obtained from the b-TCP, b-TCMP, and BCMP inks were cylinders (8 3 5 mm 2 ) composed of 21 layers, with two perimeter rims surrounding a parallel array of rods (0.33 mm) with an inter-rod spacing of, approximately, 460 lm. Those scaffolds reproduce in their architecture the typical thicknesses of the trabeculae, which are in the range of 100-300 mm, and typical intertrabecular spacing, which is in the order of 500 to 1500 mm.…”