Probing the Osteoinductive Effect of Calcium Phosphate by Using an In Vitro Biomimetic Model

The use of calcium phosphate (CaP)-based carriers in bone engineering is a promising approach to induce in vivo bone formation. However, the exact mechanism of osteoinduction by CaP is not known. Here, by mimicking the in vivo Ca2+ and P-i-enriched environment in an in vitro model, we assessed the effects of these ions on human periosteum-derived cells. We observed a significant Ca2+ and P-i-induced cell proliferation, which was found to be through the modulation of cell cycle progression, in a dose-and time-dependent manner. In addition, Ca2+, P-i, and combined Ca-P upregulated osteogenic gene expression in a dose-and time-dependent manner. Encouragingly, both ions administered individually or in combination persistently and dose dependently upregulated bone morphogenetic protein-2 gene expression. This suggested a potential osteoinductive effect through an autonomous activation of the bone morphogenetic protein signaling pathway by released Ca2+ and P-i, which may serve as an autocrine/paracrine osteoinduction loop that drives the cellularized CaP constructs toward effective bone formation in vivo. In conclusion, through an in vitro biomimetic model, we have partially probed the roles of the released Ca2+ and P-i on the osteoinductivity of CaP-based biomaterials.