title: Revisiting whitlockite, the second most abundant biomineral in bone: nanocrystal synthesis in physiologically relevant conditions and biocompatibility evaluation.
abstract: The synthesis of pure whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) has remained a challenge even though it is the second most abundant inorganic in living bone. Although a few reports about the precipitation of WH in heterogeneous phases have been published, to date, synthesizing WH without utilizing any effects of a buffer or various other ions remains difficult. Thus, the related research fields have encountered difficulties and have not been fully developed. Here, we developed a large-scale synthesis method for pure WH nanoparticles in a ternary Ca(OH)2-Mg(OH)2-H3PO4 system based on a systematic approach. We used excess Mg(2+) to impede the growth of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and the formation of other kinetically favored calcium phosphate intermediate phases. In addition, we designed and investigated the synthesis conditions of WH under the acidic pH conditions required to dissolve HAP, which is the most thermodynamically stable phase above pH 4.2, and to incorporate the HPO4(2-) group into the chemical structure of WH. We demonstrated that pure WH nanoparticles can be precipitated under Mg(2+)-rich and acidic pH conditions without any intermediate phases. Interestingly, this synthesized nano-WH showed comparable biocompatibility with HAP. Our methodology for determining the synthesis conditions of WH could provide a new platform for investigating other important precipitants in aqueous systems.
authors.affiliation: Department of Materials Science and Engineering, Seoul National University , Seoul, 151-744, Korea.
authors.forename: Hae Lin
authors.initials: HL
authors.lastname: Jang
authors.forename: Kyoungsuk
authors.initials: K
authors.lastname: Jin
authors.forename: Jaehun
authors.initials: J
authors.lastname: Lee
authors.forename: Younghye
authors.initials: Y
authors.lastname: Kim
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Nahm
authors.forename: Kug Sun
authors.initials: KS
authors.lastname: Hong
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Nam
mesh_terms: D001672:Biocompatible Materials; D001842:Bone and Bones / Q000378:metabolism*; D002130:Calcium Phosphates / Q000378:metabolism*; D002478:Cells, Cultured; D017886:Durapatite / Q000737:chemistry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; C021767:whitlockite; D017886:Durapatite