Osteoblast and osteoclast responses to chelate-setting calcium phosphate cements with different solubilities

Artificial bone grafts are widely used to treat bone defects, and paste-type materials capable of setting into arbitrary shapes offer particularly high clinical value. We previously developed a novel paste-type artificial bone, termed a chelate-setting calcium phosphate cement, which uses inositol phosphate (IP6) with strong calcium-chelating ability. Earlier studies revealed a clear relationship between the <i>in vitro</i> solubility and <i>in vivo</i> resorption behavior of this cement; however, the cellular mechanisms linking solubility to biological responses remain insufficiently understood. In this study, chelate-setting cements composed of different calcium phosphate phases, α-tricalcium phosphate (α-TCP), β-tricalcium phosphate (β-TCP), and hydroxyapatite (HAp), were fabricated to clarify how ions released from each cement influence osteoblast and osteoclast responses. The IP6/α-TCP cement showed the highest release of calcium and phosphate ions, followed by IP6/β-TCP, whereas IP6/HAp exhibited the lowest release. In osteoblast assays, cell proliferation was greatest on IP6/HAp and lowest on IP6/α-TCP. Conversely, osteoclast differentiation was most strongly promoted by IP6/β-TCP and suppressed on IP6/HAp. Overall, the β-TCP-based cement provided the most balanced cellular responses for bone formation and resorption, supporting the established view that β-TCP offers superior resorption-replacement characteristics.