Bone whitlockite: synthesis, applications, and future prospects

Bone whitlockite (WH) exists in the collagen matrix along with hydroxyapatite (HA) and plays a vital role during earlier stages of bone development. It is present in short-range order and is difficult to identify in the bone, as compared to HA mineral, that covers 80% of the bone inorganic phase. It has the same structural analogy with β-TCP, but detailed structural and crystallographic analyses of bone have shown that β-tricalcium phosphate (β-TCP) is merely a synthetic analog of bone whitlockite, having the same crystalline structure but different chemically. WH contains magnesium at Ca(IV), Ca(V) positions, and HPO42− on a threefold axis in a rhombohedral crystal lattice. Its biocompatibility, functionality, negative surface charge, mechanical strength, and stability in physiological solvents make it an ideal bone substitute as compared to hydroxyapatite (HA) and β-TCP. It has magnesium as a major component that has a strong affinity with integrin protein. Integrin protein plays a vital role in bone tissue integration. It is bioresorbable and biodegradable and the rate of degradation complements with regeneration. However, despite these excellent properties, this material has always been overshadowed by other calcium phosphates (CaPs), because it is difficult to synthesize. In this review article, we present a comprehensive study on the difference in the crystalline structure of bone whitlockite and β-TCP, its presence in the natural system, and conditions under which its nucleation occurs in native bone and at lab scale. Furthermore, the reaction conditions that favor homogenous precipitation of synthetic WH and the role of magnesium in the stabilization of different CaPs to obtain pure WH phase are also discussed. Finally, the applications of WH in biomedical and for heavy metal adsorption are summarized.