Murine osteoblastic and osteoclastic differentiation on strontium releasing hydroxyapatite forming cements

Abstract

Ionic substitutions in hydroxyapatite (HA) scaffolds and self-setting cements containing Sr2+ ions incorporated are particularly of interest in bone regeneration. To date, the approach widely used to incorporate Sr2+ ions into HA cements has been the addition of Sr2+ containing salts, such as SrCO3, SrCl2∙6H2O, or SrHPO4. However, this approach is dependent upon the relative solubility of Sr2+ containing salts with respect to calcium phosphate (CaP) precursors. Therefore, in the current study Sr2+ substituted dicalcium phosphate dihydrate (DCPD) was first synthesized and directly reacted with tetracalcium phosphate (TTCP) to form Sr2+ substituted HA forming cements. Rietveld refinement indicated that after one week of aging in phosphate buffered saline, cements prepared with and without Sr2+ were composed of 75% HA and 25% unreacted TTCP by weight. Cements prepared with 10% Sr2+ 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 Sr2+ content. It was concluded that both the scaffold microstructure and Sr2+ 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 Sr2+ released may have been too low to influence osteoclast formation in comparison to unsubstituted cements. The results obtained herein demonstrate that the use of Sr2+ substituted DCPD precursors rather than individually separate Sr2+ containing salts may be a useful approach to prepare Sr2+ containing HA cements.