Murine osteoblastic and osteoclastic differentiation on strontium releasing hydroxyapatite forming cements

Abstract

Ionic substitutions in hydroxyapatite (HA) scaffolds and self-setting cements containing Sr(2+) ions incorporated are particularly of interest in bone regeneration. To date, the approach widely used to incorporate Sr(2+) ions into HA cements has been the addition of Sr(2+) containing salts, such as SrCO3, SrCl2∙6H2O, or SrHPO4. However, this approach is dependent upon the relative solubility of Sr(2+) containing salts with respect to calcium phosphate (CaP) precursors. Therefore, in the current study Sr(2+) substituted dicalcium phosphate dihydrate (DCPD) was first synthesized and directly reacted with tetracalcium phosphate (TTCP) to form Sr(2+) substituted HA forming cements. Rietveld refinement indicated that after one week of aging in phosphate buffered saline, cements prepared with and without Sr(2+) were composed of 75% HA and 25% unreacted TTCP by weight. Cements prepared with 10% Sr(2+) DCPD exhibited increased compressive strengths in comparison to unsubstituted cements. Increased MC3T3-E1 proliferation and differentiation were also observed on the cements prepared with increasing Sr(2+) content. It was concluded that both the scaffold microstructure and Sr(2+) ion release supported osteogenic differentiation. With respect to osteoclastic differentiation, no statistically significant differences in TRAP activity or cell morphology were observed. This suggests that the amount of Sr(2+) released may have been too low to influence osteoclast formation in comparison to unsubstituted cements. The results obtained herein demonstrate that the use of Sr(2+) substituted DCPD precursors rather than individually separate Sr(2+) containing salts may be a useful approach to prepare Sr(2+) containing HA cements.

New Sintered Porous Scaffolds of Mg,Sr Co-Substituted Hydroxyapatite Support Growth and Differentiation of Primary Human Osteoblasts In Vitro

“…Interestingly, cell differentiation as assessed by alkaline phosphatase expression was increased in cells growing in contact with substituted HAs (Figure 5). This is compatible with literature showing that Mg and Sr-doped hydroxyapatite and cements increase osteoblast differentiation [31][32][33]. The increase in ALP expression was observed both along modified granules and all over the culture plate, indicating that the cellular effects were likely to be mediated by the release of bioactive ions into the culture medium.…”

Mg,Sr-Cosubstituted Hydroxyapatite with Improved Structural Properties

“…Sr is a natural bone-seeking trace element [8,10], which accumulates in the skeleton, preferably into newly formed bone [11,12], affects collagen synthesis in cell culture [9,10], and promotes osteoblastic function [13]. In vivo studies indicate that Sr, within a certain concentration range [14], increases bone formation and reduces bone resorption, thus improving bone mass and mechanical properties in both animals and humans, under normal or pathological bone conditions [11,12,[15][16][17][18].…”

Rapid Fabrication of MgNH4PO4·H2O/SrHPO4 Porous Composite Scaffolds with Improved Radiopacity via 3D Printing Process

“…When the extract concentration was 0.1 g/mL, the MgNH 4 PO 4 ·H 2 O/SrHPO 4 porous composite scaffolds with a SrHPO 4 content of 9.34% possessed enhanced cell proliferation compared to that of the pure MgNH 4 PO 4 ·H 2 O scaffolds ( Figure 9 c). The possible reason was that Sr 2+ could affect the calcium sensing receptor in a dose-dependent manner to increase the gene expression of c-fos and egr1, which are both involved in the regulation of osteoblast proliferation [ 66 , 67 ].…”