Hae Lin Jang, Hao Cheng and Ali Khademhosseini
Brigham and Women’s Hospital, Harvard Medical School, USA
Human hard tissue is mainly composed of the two nanocrystals, hydroxyapatite (Ca10(PO4)6(OH)2) and whitlockite (Ca18Mg2(HPO4)2(PO4)12). Hydroxyapatite is one of the most thermodynamically stable calcium phosphates in physiological condition. Whitlockite is estimated to occupy approximately 20 wt% of bone minerals and is the only crystal that can continuously supply Mg2+ ions in human body, while Mg2+ ions can promote bone formation. As a result, whitlockite can enhance osteogenesis than hydroxyapatite. On the other hand, hydroxyapatite can provide mechanically more stable 3D microenvironment for cells based on its lower solubility than whitlockite, since excessive free ions released from minerals can disturb hydrogel network. In this respect, we hypothesized that nanocomposite hydrogel scaffolds with optimized ratio between hydroxyapatite and whitlockite could provide both mechanically and biologically favorable 3D matrix for bone cells. To verify this hypothesis, we regulated the ratio of the two mineral types in 3D cell-laden hydrogel scaffolds. Notably, when the ratio between hydroxyapatite and whitlockite was approximately 3 to 1 and became similar to native bone tissue, the osteogenic activity of cells was maximized, both in vitro and in vivo. This is the first study for understanding the biological significance of the ratio between the two major minerals in bone.