Abstract
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.
Similar content being viewed by others
References
Y. Zhou, C. Wu, J. Chang, Bioceramics to regulate stem cells and their microenvironment for tissue regeneration. Mater. Today. 24, 41–56 (2019). https://doi.org/10.1016/j.mattod.2018.07.016
J. Jeong, J.H. Kim, J.H. Shim, N.S. Hwang, C.Y. Heo, Bioactive calcium phosphate materials and applications in bone regeneration. Biomaterial. Res. (2019). https://doi.org/10.1186/s40824-018-0149-3
S.R. Paital, N.B. Dahotre, Calcium phosphate coatings for bio-implant applications: Materials, performance factors, and methodologies. Mater. Sci. Eng. R Reports. 66, 1–70 (2009). https://doi.org/10.1016/j.mser.2009.05.001
M. Vallet-Regí, I. Izquierdo-Barba, M. Colilla, Structure and functionalization of mesoporous bioceramics for bone tissue regeneration and local drug delivery. Philos. Trans. R. Soc. A Math. Phys. Eng. Sci. 370, 1400–1421 (2012). https://doi.org/10.1098/rsta.2011.0258
W. Habraken, P. Habibovic, M. Epple, M. Bohner, Calcium phosphates in biomedical applications: materials for the future? Mater. Today 19, 69–87 (2016). https://doi.org/10.1016/j.mattod.2015.10.008
L.C. Gerhardt, A.R. Boccaccini, Bioactive glass and glass-ceramic scaffolds for bone tissue engineering. Materials (Basel). 3, 3867–3910 (2010). https://doi.org/10.3390/ma3073867
F. Barrère, C.A. van Blitterswijk, K. de Groot, Bone regeneration: Molecular and cellular interactions with calcium phosphate ceramics. Int. J. Nanomed. 1, 317–332 (2006)
S. Kuttappan, D. Mathew, M.B. Nair, Biomimetic composite scaffolds containing bioceramics and collagen/gelatin for bone tissue engineering—a mini review. Int. J. Biol. Macromol. 93, 1390–1401 (2016). https://doi.org/10.1016/j.ijbiomac.2016.06.043
V.P. Mantripragada, B. Lecka-Czernik, N.A. Ebraheim, A.C. Jayasuriya, An overview of recent advances in designing orthopedic and craniofacial implants. J. Biomed. Mater. Res. Part A. 101, 3349–3364 (2013). https://doi.org/10.1002/jbm.a.34605
P.N. Kumta, C. Sfeir, D.H. Lee, D. Olton, D. Choi, Nanostructured calcium phosphates for biomedical applications: Novel synthesis and characterization. Acta Biomater. 1, 65–83 (2005). https://doi.org/10.1016/j.actbio.2004.09.008
S. Bose, S. Tarafder, Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: a review. Acta Biomater. 8, 1401–1421 (2012). https://doi.org/10.1016/j.actbio.2011.11.017
V. Uskoković, D.P. Uskoković, Nanosized hydroxyapatite and other calcium phosphates: chemistry of formation and application as drug and gene delivery agents. J. Biomed. Mater. Res. Part B Appl. Biomater. 96B, 152–191 (2011). https://doi.org/10.1002/jbm.b.31746
I. Ullah, A. Gloria, W. Zhang, M.W. Ullah, B. Wu, W. Li, M. Domingos, X. Zhang, Synthesis and characterization of sintered Sr/Fe-modified hydroxyapatite bioceramics for bone tissue engineering applications. ACS Biomater. Sci. Eng. 6, 375–388 (2020). https://doi.org/10.1021/acsbiomaterials.9b01666
A. Haider, S. Haider, S. Han, I. Kang, Recent advances in the synthesis, functionalization and biomedical applications of hydroxyapatite. RSC Adv. (2017). https://doi.org/10.1039/c6ra26124h
R. Yunus Basha, S.K. Sampath, M. Doble, Design of biocomposite materials for bone tissue regeneration. Mater. Sci. Eng. C 57, 452–463 (2015). https://doi.org/10.1016/j.msec.2015.07.016
C. Lin, H. Zhu, Y. Zeng, Sr- and Si-containing bioceramic stimulate in vitro osteogenesis. Surf. Coat. Technol. 365, 129–133 (2019). https://doi.org/10.1016/j.surfcoat.2018.10.063
J.H. Chung, Y.K. Kim, K.H. Kim, T.Y. Kwon, S.Z. Vaezmomeni, M. Samiei, M. Aghazadeh, S. Davaran, M. Mahkam, G. Asadi, A. Akbarzadeh, Synthesis, characterization, biocompatibility of hydroxyapatite-natural polymers nanocomposites for dentistry applications. Artif. Cells Nanomed. Biotechnol. 44, 277–284 (2016). https://doi.org/10.3109/21691401.2014.944644
A.S. Kranthi Kiran, A. Kizhakeyil, R. Ramalingam, N.K. Verma, R. Lakshminarayanan, T.S.S. Kumar, M. Doble, S. Ramakrishna, Drug loaded electrospun polymer/ceramic composite nanofibrous coatings on titanium for implant related infections. Ceram. Int. 45, 18710–18720 (2019). https://doi.org/10.1016/j.ceramint.2019.06.097
P. Habibovic, J.E. Barralet, Bioinorganics and biomaterials: bone repair. Acta Biomater. 7, 3013–3026 (2011). https://doi.org/10.1016/j.actbio.2011.03.027
A. Hertz, I.J. Bruce, Inorganic materials for bone repair or replacement applications. Nanomedicine 2, 899–918 (2007). https://doi.org/10.2217/17435889.2.6.899
A.M. Brokesh, A.K. Gaharwar, Inorganic biomaterials for regenerative medicine. ACS Appl. Mater. Interfaces 12, 5319–5344 (2020). https://doi.org/10.1021/acsami.9b17801
M. Trabelsi, I. AlShahrani, H. Algarni, F. Ben-Ayed, E.S. Yousef, Mechanical and tribological properties of the tricalcium phosphate—magnesium oxide composites. Mater. Sci. Eng. C. 96, 716–729 (2019). https://doi.org/10.1016/j.msec.2018.11.070
M. Razavi, M.H. Fathi, M. Meratian, Fabrication and characterization of magnesium—fluorapatite nanocomposite for biomedical applications. Mater. Charact. 61, 1363–1370 (2010). https://doi.org/10.1016/j.matchar.2010.09.008
A. Jense, S. Rowles, Lattice constants and magnesium contents of some naturally occurring whitlockites. Nature 179, 912–913 (1957). https://doi.org/10.1038/179912b0
A.T. Saleh, L.S. Ling, R. Hussain, Injectable magnesium-doped brushite cement for controlled drug release application. J. Mater. Sci. 51, 7427–7439 (2016). https://doi.org/10.1007/s10853-016-0017-2
H.L. Jang, K. Jin, J. Lee, Y. Kim, S.H. Nahm, K.S. Hong, K.T. Nam, Revisiting whitlockite, the second most abundant biomineral in bone: Nanocrystal synthesis in physiologically relevant conditions and biocompatibility evaluation. ACS Nano 8, 634–641 (2014). https://doi.org/10.1021/nn405246h
A. Altomare, R. Rizzi, M. Rossi, A. El Khouri, M. Elaatmani, V. Paterlini, I. Della Ventura, F. Capitelli, New Ca2.90(Me2+)0.10(PO4)2(β-tricalcium phosphates with Me2+= Mn, Ni, Cu: synthesis, crystal-chemistry, and luminescence properties. Curr. Comput.-Aided Drug Des. 9, 1–17 (2019). https://doi.org/10.3390/cryst9060288
A.T. Jensen, S.L. Rowles, Magnesian whitlockite, a major constituent of dental calculus. Acta Odontol. Scand. 15, 121–139 (1957). https://doi.org/10.3109/00016355709041096
K.D. Litasov, N.M. Podgornykh, Raman spectroscopy of various phosphate minerals and occurrence of tuite in the Elga IIE iron meteorite. J. Raman Spectrosc. 48, 1518–1527 (2017). https://doi.org/10.1002/jrs.5119
J.M. Hughes, B.L. Jolliff, J. Rakovan, The crystal chemistry of whitlockite and merrillite and the dehydrogenation of whitlockite to merrillite. Am. Mineral. 93, 1300–1305 (2008). https://doi.org/10.2138/am.2008.2683
C. Stähli, J. Thüring, L. Galea, S. Tadier, M. Bohner, N. Döbelin, Hydrogen-substituted β-tricalcium phosphate synthesized in organic media. Acta Crystallogr. Sect. B Struct. Sci. Cryst. Eng. Mater. 72, 875–884 (2016). https://doi.org/10.1107/S2052520616015675
P. Melnikov, D.M. de Albuquerque, T.A. Naves, L.C.S. de Oliveira, Synthesis and characterization of zinc-containing whitlockite Ca10Zn10H2(PO4)14 for orthopedic applications. Mater. Lett. 231, 198–200 (2018). https://doi.org/10.1016/j.matlet.2018.08.051
R. Lagier, C.A. Baud, Magnesium whitlockite, a calcium phosphate crystal of special interest in pathology. Pathol. Res. Pract. 199, 329–335 (2003). https://doi.org/10.1078/0344-0338-00425
C.T. Adcock, O. Tschauner, E.M. Hausrath, A. Udry, S.N. Luo, Y. Cai, M. Ren, A. Lanzirotti, M. Newville, M. Kunz, C. Lin, Shock-transformation of whitlockite to merrillite and the implications for meteoritic phosphate. Nat. Commun. 8, 1–8 (2017). https://doi.org/10.1038/ncomms14667
M. Canillas, P. Pena, A.H. De Aza, M.A. Rodríguez, Calcium phosphates for biomedical applications. Bol. La Soc. Esp. Ceram. y Vidr. 56, 91–112 (2017). https://doi.org/10.1016/j.bsecv.2017.05.001
R. Gopal, C. Calvo, J. Ito, W.K. Sabine, Crystal structure of synthetic Mg-whitlockite, Ca18Mg2H2(PO4)14. Can J Chem 52(7), 1155–1164 (2020). https://doi.org/10.1139/v74-181
J.S. Bow, S.C. Liou, S.Y. Chen, Structural characterization of room-temperature synthesized nano-sized β-tricalcium phosphate. Biomaterials 25, 3155–3161 (2004). https://doi.org/10.1016/j.biomaterials.2003.10.046
T.A. Grünewald, H. Rennhofer, B. Hesse, M. Burghammer, S.E. Stanzl-tschegg, M. Cotte, J.F. Löffler, A.M. Weinberg, H.C. Lichtenegger, Biomaterials magnesium from bioresorbable implants: distribution and impact on the nano- and mineral structure of bone. Biomaterials 76, 250–260 (2016). https://doi.org/10.1016/j.biomaterials.2015.10.054
M. Diba, F. Tapia, A.R. Boccaccini, L.A. Strobel, Magnesium-containing bioactive glasses for biomedical applications. Int. J. Appl. Glas. Sci. 3, 221–253 (2012). https://doi.org/10.1111/j.2041-1294.2012.00095.x
V. Campana, G. Milano, E. Pagano, M. Barba, C. Cicione, G. Salonna, W. Lattanzi, G. Logroscino, Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J. Mater. Sci. Mater. Med. 25, 2445–2461 (2014). https://doi.org/10.1007/s10856-014-5240-2
S.V. Dorozhkin, Calcium orthophosphate-based biocomposites and hybrid biomaterials. J. Mater. Sci. 44, 2343–2387 (2009). https://doi.org/10.1007/s10853-008-3124-x
Y.Z. Jin, G. Bin Zheng, H.L. Jang, K.M. Lee, J.H. Lee, Whitlockite promotes bone healing in rabbit ilium defect model. J. Med. Biol. Eng. 39, 944–951 (2019). https://doi.org/10.1007/s40846-019-00471-0
S. Gomes, G. Renaudin, E. Jallot, J.M. Nedelec, Structural characterization and biological fluid interaction of sol-gel-derived Mg-substituted biphasic calcium phosphate ceramics. ACS Appl. Mater. Interfaces 1, 505–513 (2009). https://doi.org/10.1021/am800162a
D.V. Deyneko, S.M. Aksenov, V.A. Morozov, S.Y. Stefanovich, O.V. Dimitrova, O.V. Barishnikova, B.I. Lazoryak, A new hydrogen-containing whitlockitetype phosphate Ca9(Fe0.63Mg0.37)H0.37(PO4)7: hydrothermal synthesis and structure. Zeitschrift Fur Krist. Cryst. Mater. 229, 823–830 (2014). https://doi.org/10.1515/zkri-2014-1774
B.I. Lazoryak, T.V. Strunenkova, V.N. Golubev, E.A. Vovk, L.N. Ivanov, Triple phosphates of calcium, sodium and trivalent elements with whitlockite-like structure. Mater. Res. Bull. 31, 207–216 (1996). https://doi.org/10.1016/0025-5408(95)00181-6
C.A. Scotchford, M. Vickers, S. Yousuf Ali, The isolation and characterization of magnesium whitlockite crystals from human articular cartilage. Osteoarthr. Cartil. 3, 79–94 (1995). https://doi.org/10.1016/S1063-4584(05)80041-X
R.P. Shellis, B.R. Heywood, F.K. Wahab, Formation of brushite, monetite and whitlockite during equilibration of human enamel with acid solutions at 37 degrees C. Caries Res. 31, 71–77 (1997). https://doi.org/10.1159/000262377
F.A. Shah, B.E.J. Lee, J. Tedesco, C. Larsson Wexell, C. Persson, P. Thomsen, K. Grandfield, A. Palmquist, Micrometer-sized magnesium whitlockite crystals in micropetrosis of bisphosphonate-exposed human alveolar bone. Nano Lett. 17, 6210–6216 (2017). https://doi.org/10.1021/acs.nanolett.7b02888
M. López-Álvarez, S. Pérez-Davila, C. Rodríguez-Valencia, P. González, J. Serra, The improved biological response of shark tooth bioapatites in a comparative in vitro study with synthetic and bovine bone grafts. Biomed. Mater. (2016). https://doi.org/10.1088/1748-6041/11/3/035011
D.H. Butler, R. Shahack-Gross, Formation of biphasic hydroxylapatite-beta magnesium tricalcium phosphate in heat treated salmonid vertebrae. Sci. Rep. 7, 1–11 (2017). https://doi.org/10.1038/s41598-017-03737-2
J.H. Luna-Domínguez, H. Téllez-Jiménez, H. Hernández-Cocoletzi, M. García-Hernández, J.A. Melo-Banda, H. Nygren, Development and in vivo response of hydroxyapatite/whitlockite from chicken bones as bone substitute using a chitosan membrane for guided bone regeneration. Ceram. Int. 44, 22583–22591 (2018). https://doi.org/10.1016/j.ceramint.2018.09.032
C.A. Scotchford, S.Y. Ali, Association of magnesium whitlockite crystals with lipid components of the extracellular matrix in human articular cartilage. Osteoarthr. Cartil. 5, 107–119 (1997). https://doi.org/10.1016/S1063-4584(97)80004-0
T. Debroise, E. Colombo, G. Belletti, J. Vekeman, Y. Su, R. Papoular, N.S. Hwang, D. Bazin, M. Daudon, P. Quaino, F. Tielens, One step further in the elucidation of the crystallographic structure of whitlockite. Cryst. Growth Des. (2020). https://doi.org/10.1021/acs.cgd.9b01679
A.R. Toibah, I. Sopyan, M. Hamdi, S. Ramesh, Development of magnesium-doped biphasic calcium phosphatethrough sol-gel method. In: 4th Kuala Lumpur International Conference on Biomedical Engineering (2008). IFMBE Proceedings, vol. 21, ed. by N.A. Abu Osman, F. Ibrahim, W.A.B. Wan Abas, H.S. Abdul Rahman, H.N. Ting (Springer, Berlin), pp. 314–317. https://doi.org/10.1007/978-3-540-69139-6_80
S.M. Naga, A.M. Hassan, M. Awaad, A. Killinger, R. Gadow, A. Bernstein, M. Sayed, Forsterite/nano-biogenic hydroxyapatite composites for biomedical applications. J. Asian Ceram. Soc. 00, 1–14 (2020). https://doi.org/10.1080/21870764.2020.1743416
J. Cabrejos-Azama, M.H. Alkhraisat, C. Rueda, J. Torres, L. Blanco, E. López-Cabarcos, Magnesium substitution in brushite cements for enhanced bone tissue regeneration. Mater. Sci. Eng. C. 43, 403–410 (2014). https://doi.org/10.1016/j.msec.2014.06.036
E. O’Neill, G. Awale, L. Daneshmandi, O. Umerah, K.W.H. Lo, The roles of ions on bone regeneration. Drug Discov. Today. 23, 879–890 (2018). https://doi.org/10.1016/j.drudis.2018.01.049
M. Nabiyouni, T. Brückner, H. Zhou, U. Gbureck, S.B. Bhaduri, Magnesium-based bioceramics in orthopedic applications. Acta Biomater. 66, 23–43 (2018). https://doi.org/10.1016/j.actbio.2017.11.033
S. Yoshizawa, A. Brown, A. Barchowsky, C. Sfeir, Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater. 10, 2834–2842 (2014). https://doi.org/10.1016/j.actbio.2014.02.002
M. Shahrezaee, M. Raz, S. Shishehbor, F. Moztarzadeh, F. Baghbani, A. Sadeghi, K. Bajelani, F. Tondnevis, Synthesis of magnesium doped amorphous calcium phosphate as a bioceramic for biomedical application: in vitro study. SILICON 10, 1171–1179 (2018). https://doi.org/10.1007/s12633-017-9589-y
Y.T. Sul, P. Johansson, B.S. Chang, E.S. Byon, Y. Jeong, Bone tissue responses to Mg-incorporated oxidized implants and machine-turned implants in the rabbit femur. J. Appl. Biomater. Biomech. 3, 18–28 (2005). https://doi.org/10.1177/228080000500300103
M.P. Staiger, A.M. Pietak, J. Huadmai, G. Dias, Magnesium and its alloys as orthopedic biomaterials: a review. Biomaterials 27, 1728–1734 (2006). https://doi.org/10.1016/j.biomaterials.2005.10.003
M.M. Belluci, G. Giro, R.A.L. del Barrio, R.M.R. Pereira, E. Marcantonio, S.R.P. Orrico, Effects of magnesium intake deficiency on bone metabolism and bone tissue around osseointegrated implants. Clin. Oral Implants Res. 22, 716–721 (2011). https://doi.org/10.1111/j.1600-0501.2010.02046.x
B. Gayathri, N. Muthukumarasamy, D. Velauthapillai, S.B. Santhosh, V. Asokan, Magnesium incorporated hydroxyapatite nanoparticles: preparation, characterization, antibacterial and larvicidal activity. Arab. J. Chem. 11, 645–654 (2018). https://doi.org/10.1016/j.arabjc.2016.05.010
S. Kannan, A.F. Lemos, J.H.G. Rocha, J.M.F. Ferreira, Characterization and mechanical performance of the Mg-stabilized $β$-Ca3(PO4)2 prepared from Mg-substituted Ca-deficient apatite. J. Am. Ceram. Soc. 89, 2757–2761 (2006). https://doi.org/10.1111/j.1551-2916.2006.01158.x
M.H. Marahat, M.A.A. Zahari, H. Mohamad, S.R. Kasim, Effect of magnesium ion (Mg2+) substitution and calcination to the properties of biphasic calcium phosphate (BCP). In: AIP Conference Proceedings, vol. 2068 (2019). https://doi.org/10.1063/1.5089373
J. Liao, K. Hamada, M. Senna, Synthesis of Ca–Mg apatite via a mechanochemical hydrothermal process. J. Mater. Synth. Process. 8, 305–306 (2000). https://doi.org/10.1023/A:1011342427619
W.L. Suchanek, K. Byrappa, P. Shuk, R.E. Riman, V.F. Janas, K.S. Tenhuisen, Mechanochemical-hydrothermal synthesis of calcium phosphate powders with coupled magnesium and carbonate substitution. J. Solid State Chem. 177, 793–799 (2004). https://doi.org/10.1016/j.jssc.2003.09.012
S.N. Danilchenko, I.Y. Protsenko, L.F. Sukhodub, Some features of thermo-activated structural transformation of biogenic and synthetic Mg-containing apatite with ß-tricalciummagnesium phosphate formation. Cryst. Res. Technol. 44, 553–560 (2009). https://doi.org/10.1002/crat.200900017
L. Wang, C. Peng, Y. Song, IFES sciences for life Ni@carbon nanocomposites/macroporous carbon for glucose sensor. J. Mater. Sci. 54, 1654–1664 (2019). https://doi.org/10.1007/s10853-018-2878-z
S. Adzila, N.A. Mustaffa, N. Kanasan, Magnesium-doped calcium phosphate/sodium alginate biocomposite for bone implant application. J. Aust. Ceram. Soc. (2020). https://doi.org/10.1007/s41779-019-00417-4
H. Zhou, S. Hou, M. Zhang, H. Chai, Y. Liu, S.B. Bhaduri, L. Yang, L. Deng, Synthesis of β-TCP and CPP containing biphasic calcium phosphates by a robust technique. Ceram. Int. 42, 11032–11038 (2016). https://doi.org/10.1016/j.ceramint.2016.03.246
T. Sakae, X-ray diffraction and thermal studies of I Iii. Archs Oral Biol. 33, 707–713 (1988)
J.D.B. Featherstone, I. Mayer, F.C.M. Driessens, R.M.H. Verbeeck, H.J.M. Heijligers, Synthetic apatites containing Na, Mg, and CO3 and their comparison with tooth enamel mineral. Calcif. Tissue Int. 35, 169–171 (1983). https://doi.org/10.1007/BF02405026
M.H. Salimi, J.C. Heughebaert, G.H. Nancollas, Crystal growth of calcium phosphates in the presence of magnesium ions. Langmuir 1, 119–122 (1985). https://doi.org/10.1021/la00061a019
M. Okazaki, J. Takahashi, H. Kimura, Unstable behavior of magnesium-containing hydroxyapatites. Caries Res. 20, 324–331 (1986)
N. Kanzaki, K. Onuma, G. Treboux, S. Tsutsumi, A. Ito, Inhibitory effect of magnesium and zinc on crystallization kinetics of hydroxyapatite (0001) face. J. Phys. Chem. B. 104, 4189–4194 (2000). https://doi.org/10.1021/jp9939726
M. Nouri-Felekori, M. Khakbiz, N. Nezafati, Synthesis and characterization of Mg, Zn and Sr-incorporated hydroxyapatite whiskers by hydrothermal method. Mater. Lett. 243, 120–124 (2019). https://doi.org/10.1016/j.matlet.2019.01.147
S.R. Kim, J.H. Lee, Y.T. Kim, D.H. Riu, S.J. Jung, Y.J. Lee, S.C. Chung, Y.H. Kim, Synthesis of Si, Mg substituted hydroxyapatites and their sintering behaviors. Biomaterial 24, 1389–1398 (2003). https://doi.org/10.1016/S0142-9612(02)00523-9
S. Diallo-Garcia, D. Laurencin, J.M. Krafft, S. Casale, M.E. Smith, H. Lauron-Pernot, G. Costentin, Influence of magnesium substitution on the basic properties of hydroxyapatites. J. Phys. Chem. C. 115, 24317–24327 (2011). https://doi.org/10.1021/jp209316k
L. Bauer, M. Ivanković, H. Ivanković, Magneisum substituted hydroxyapatite scaffolds hydrothermally synthesized from Cuttlefish bone. In: International Conference MATRIB (2018), vol. 21–34. Croatian Society for Materials and Tribology
I. Cacciotti, A. Bianco, M. Lombardi, L. Montanaro, Mg-substituted hydroxyapatite nanopowders: synthesis, thermal stability and sintering behaviour. J. Eur. Ceram. Soc. 29, 2969–2978 (2009). https://doi.org/10.1016/j.jeurceramsoc.2009.04.038
I.V. Fadeev, L.I. Shvorneva, S.M. Barinov, V.P. Orlovskii, Synthesis and structure of magnesium-substituted hydroxyapatite. Inorg. Mater. 39, 947–950 (2003)
S. Kannan, I.A.F. Lemos, J.H.G. Rocha, J.M.F. Ferreira, Synthesis and characterization of magnesium substituted biphasic mixtures of controlled hydroxyapatite/β-tricalcium phosphate ratios. J. Solid State Chem. 178, 3190–3196 (2005). https://doi.org/10.1016/j.jssc.2005.08.003
L. Stipniece, K. Salma-Ancane, D. Jakovlevs, N. Borodajenko, L. Berzina-Cimdina, The study of magnesium substitution effect on physicochemical properties of hydroxyapatite. Mater. Sci. Appl. Chem. 28, 51 (2013). https://doi.org/10.7250/msac.2013.009
I. Manjubala, T.S. Sampath Kumar, Preparation of biphasic calcium phosphate doped with magnesium fluoride for osteoporotic applications. J. Mater. Sci. Lett. 20, 1225–1227 (2001). https://doi.org/10.1023/A:1010926923815
K. Hashimoto, T. Khajihara, Y. Toda, T. Kanazawa, Preparation of (Mg,Fe)-containing whitlockite ceramics. Phosphorus Res. Bull. 10, 329–334 (1999). https://doi.org/10.3363/prb1992.10.0_329
J.S. Rabelo Neto, T.B. Knopf, M.C. Fredel, S. Olate, P.H. de Moraes, Synthesis and characterization of calcium phosphate compounds with strontium and magnesium ionic substitutions. Int. J. Morphol. 33, 1189–1193 (2015). https://doi.org/10.4067/s0717-95022015000300061
S. Ben-Moussa, A. Mehri, M. Gruselle, P. Beaunier, G. Costentin, B. Badraoui, Combined effect of magnesium and amino glutamic acid on the structure of hydroxyapatite prepared by hydrothermal method. Mater. Chem. Phys. 212, 21–29 (2018). https://doi.org/10.1016/j.matchemphys.2018.03.017
I.R. Gibson, W. Bonfield, Preparation and characterization of magnesium/carbonate co-substituted hydroxyapatites. J. Mater. Sci. Mater. Med. 13, 685–693 (2002). https://doi.org/10.1023/A:1015793927364
I. Mayer, J.D.B. Featherstone, N. Noejovichd, D. Gedalia, The thermal decomposition of Mg-containing carbonate apatites. J. Solid State Chem. 235, 230–235 (1985). https://doi.org/10.1016/0022-4596(85)90060-X
L.A. Rasskazova, I.V. Zhuk, N.M. Korotchenko, A.S. Brichkov, Y.W. Chen, E.A. Paukshtis, V.K. Ivanov, I.A. Kurzina, V.V. Kozik, Synthesis of magnesium- and silicon-modified hydroxyapatites by microwave-assisted method. Sci. Rep. 9, 1–10 (2019). https://doi.org/10.1038/s41598-019-50777-x
F. Ren, Y. Leng, R. Xin, X. Ge, Synthesis, characterization and ab initio simulation of magnesium-substituted hydroxyapatite. Acta Biomater. 6, 2787–2796 (2010). https://doi.org/10.1016/j.actbio.2009.12.044
W.L. Suchanek, K. Byrappa, P. Shuk, R.E. Riman, V.F. Janas, K.S. Tenhuisen, Preparation of magnesium-substituted hydroxyapatite powders by the mechanochemical–hydrothermal method. Biomaterials 25, 4647–4657 (2004). https://doi.org/10.1016/j.biomaterials.2003.12.008
X. Li, A. Ito, Y. Sogo, X. Wang, R.Z. LeGeros, Solubility of Mg-containing β-tricalcium phosphate at 25 °C. Acta Biomater. 5, 508–517 (2009). https://doi.org/10.1016/j.actbio.2008.06.010
A. Hanifi, M.H. Fathi, H.M.M. Sadeghi, J. Varshosaz, Mg2+ substituted calcium phosphate nano particles synthesis for non viral gene delivery application. J. Mater. Sci. Mater. Med. 21, 2393–2401 (2010). https://doi.org/10.1007/s10856-010-4088-3
S. Kannan, J.M. Ventura, J.M.F. Ferreira, Aqueous precipitation method for the formation of Mg-stabilized β-tricalcium phosphate: an X-ray diffraction study. Ceram. Int. 33, 637–641 (2007). https://doi.org/10.1016/j.ceramint.2005.11.014
S. Kannan, A.F. Lemos, J.H.G. Rocha, J.M.F. Ferreira, Characterization and mechanical performance of the Mg-stabilized β-Ca3(PO4)2 prepared from Mg-substituted Ca-deficient apatite. J. Am. Ceram. Soc. 89, 2757–2761 (2006)
M.S. Sader, R.Z. Legeros, G.A. Soares, Human osteoblasts adhesion and proliferation on magnesium-substituted tricalcium phosphate dense tablets. J. Mater. Sci. Mater. Med. 20, 521–527 (2009). https://doi.org/10.1007/s10856-008-3610-3
J.C. Araújo, M.S. Sader, E.L. Moreira, V.C.A. Moraes, R.Z. LeGeros, G.A. Soares, Maximum substitution of magnesium for calcium sites in Mg-β-TCP structure determined by X-ray powder diffraction with the Rietveld refinement. Mater. Chem. Phys. 118, 337–340 (2009). https://doi.org/10.1016/j.matchemphys.2009.07.064
D.S. Tavares, L.O. de Castro, G.D.A. de Soares, G.G. Alves, J.M. Granjeiro, Synthesis and cytotoxicity evaluation of granular magnesium substituted β-tricalcium phosphate. J. Appl. Oral Sci. 21, 37–42 (2013)
R.C. Richard, M.S. Sader, J. Dai, R.M.S.M. Thiré, G.D.A. Soares, Beta-type calcium phosphates with and without magnesium: From hydrolysis of brushite powder to robocasting of periodic scaffolds. J. Biomed. Mater. Res. Part A. 102, 3685–3692 (2014). https://doi.org/10.1002/jbm.a.35040
K. Salma-Ancane, L. Stipniece, A. Putnins, L. Berzina-Cimdina, Development of Mg-containing porous β-tricalcium phosphate scaffolds for bone repair. Ceram. Int. 41, 4996–5004 (2015). https://doi.org/10.1016/j.ceramint.2014.12.065
N.A. Moslim, N. Ahmad, S.R. Kasim, Effect of Mg concentrations on the properties of biphasic calcium phosphate (BCP). In: AIP Conference Proceedings, vol. 2068 (2019). https://doi.org/10.1063/1.5089382
R. Sasidharan Pillai, V.M. Sglavo, Effect of MgO addition on solid state synthesis and thermal behavior of beta-tricalcium phosphate. Ceram. Int. 41, 2512–2518 (2015). https://doi.org/10.1016/j.ceramint.2014.10.073
S. Ben Abdelkader, I. Khattech, C. Rey, M. Jemal, Synthése, caractérisation et thermochimie d’apatites calco-magnésiennes hydroxylées et fluorées. Thermochim. Acta. 376, 25–36 (2001). https://doi.org/10.1016/s0040-6031(01)00565-2
M.C.F. Magalhães, M.O.G. Costa, On the solubility of whitlockite, Ca9Mg(HPO4)(PO4)6, in aqueous solution at 298.15 K. Monatshefte Fur Chemie. 149, 253–260 (2018). https://doi.org/10.1007/s00706-017-2129-z
G.C. Li, P. Wang, C.B. Liu, Hydrothermal synthesis of whitlockite. J. Inorg. Mater. 32, 1128–1132 (2017). https://doi.org/10.15541/jim20160704
A.C. Tas, Transformation of brushite (CaHPO4·2H2O) to whitlockite (Ca9Mg(HPO4)(PO4)6) or other CaPs in physiologically relevant solutions. J. Am. Ceram. Soc. 99, 1200–1206 (2016). https://doi.org/10.1111/jace.14069
A. Yücel, K. Onar, C.C. Turan, T. Depci, M.E. Yakıncı, Synthesis of nano size whitlockite bioceramic precursor from Sea Urchin skeleton. TIP TEKNO 16 Anatyla (2016), pp. 348–350
J. Trinkunaite-Felsen, Z. Stankeviciute, J.C. Yang, T.C.K. Yang, A. Beganskiene, A. Kareiva, Calcium hydroxyapatite/whitlockite obtained from dairy products: simple, environmentally benign and green preparation technology. Ceram. Int. 40, 12717–12722 (2014). https://doi.org/10.1016/j.ceramint.2014.04.120
C. Qi, F. Chen, J. Wu, Y.J. Zhu, C.N. Hao, J.L. Duan, Magnesium whitlockite hollow microspheres: a comparison of microwave-hydrothermal and conventional hydrothermal syntheses using fructose 1,6-bisphosphate, and application in protein adsorption. RSC Adv. 6, 33393–33402 (2016). https://doi.org/10.1039/c6ra00775a
C.C. Lin, Y. Wang, Y. Zhou, Y. Zeng, A rapid way to synthesize magnesium whitlockite microspheres for high efficiency removing heavy metals. Desalin. Water Treat. 162, 220–227 (2019). https://doi.org/10.5004/dwt.2019.24290
X. Guo, X. Liu, H. Gao, X. Shi, N. Zhao, Y. Wang, Hydrothermal growth of whitlockite coating on β-tricalcium phosphate surfaces for enhancing bone repair potential. J. Mater. Sci. Technol. 34, 1054–1059 (2018). https://doi.org/10.1016/j.jmst.2017.07.009
C. Wang, K.J. Jeong, H.J. Park, M. Lee, S.C. Ryu, D.Y. Hwang, K.H. Nam, I.H. Han, J. Lee, Synthesis and formation mechanism of bone mineral, whitlockite nanocrystals in tri-solvent system. J. Colloid Interface Sci. 569, 1–11 (2020). https://doi.org/10.1016/j.jcis.2020.02.072
S. Batool, U. Liaqat, Z. Hussain, M. Sohail, Synthesis, characterization and process optimization of bone whitlockite. Nanomaterials 10, 1–14 (2020). https://doi.org/10.3390/nano10091856
G. Jose, K.T. Shalumon, H.T. Liao, C.Y. Kuo, J.P. Chen, Preparation and characterization of surface heat sintered nanohydroxyapatite and nanowhitlockite embedded poly (lactic-co-glycolic acid) microsphere bone graft scaffolds: In vitro and in vivo studies. Int. J. Mol. Sci. 21, 1–20 (2020). https://doi.org/10.3390/ijms21020528
Y. Chang, R. Zhao, H. Wang, L. Pang, J. Ding, Y. Shen, Y. Guo, D. Wang, A novel injectable whitlockite-containing borosilicate bioactive glass cement for bone repair. J. Non Cryst. Solids. 547, 120291 (2020). https://doi.org/10.1016/j.jnoncrysol.2020.120291
A. Yücel, S. Sezer, E. Birhanlı, T. Ekinci, E. Yalman, T. Depci, Synthesis and characterization of whitlockite from sea urchin skeleton and investigation of antibacterial activity. Ceram. Int. (2020). https://doi.org/10.1016/j.ceramint.2020.08.170
L. Bauer, M. Antunović, A. Rogina, M. Ivanković, H. Ivanković, Bone-mimetic porous hydroxyapatite/whitlockite scaffolds: preparation, characterization and interactions with human mesenchymal stem cells. J. Mater. Sci. (2020). https://doi.org/10.1007/s10853-020-05489-3
H.L. Jang, G. Bin Zheng, J. Park, H.D. Kim, H.R. Baek, H.K. Lee, K. Lee, H.N. Han, C.K. Lee, N.S. Hwang, J.H. Lee, K.T. Nam, In vitro and in vivo evaluation of whitlockite biocompatibility: comparative study with hydroxyapatite and β-tricalcium phosphate. Adv. Healthc. Mater. 5, 128–136 (2016). https://doi.org/10.1002/adhm.201400824
M. Hu, F. Xiao, Q.F. Ke, Y. Li, X.D. Chen, Y.P. Guo, Cerium-doped whitlockite nanohybrid scaffolds promote new bone regeneration via SMAD signaling pathway. Chem. Eng. J. 359, 1–12 (2019). https://doi.org/10.1016/j.cej.2018.11.116
Y. Yang, H. Wang, H. Yang, Y. Zhao, J. Guo, X. Yin, T. Ma, X. Liu, L. Li, Magnesium-based whitlockite bone mineral promotes neural and osteogenic activities. ACS Biomater. Sci. Eng. 6, 5785–5796 (2020). https://doi.org/10.1021/acsbiomaterials.0c00852
N. Sundaram, M. Pillai, K. Eswar, S. Amirthalingam, U. Mony, P.K. Varma, R. Jayakumar, Injectable nano whitlockite incorporated chitosan hydrogel for effective hemostasis. CS Appl. Bio Mater. 2, 865–873 (2019). https://doi.org/10.1021/acsabm.8b00710
Author information
Authors and Affiliations
Corresponding authors
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Batool, S., Liaqat, U., Babar, B. et al. Bone whitlockite: synthesis, applications, and future prospects. J. Korean Ceram. Soc. 58, 530–547 (2021). https://doi.org/10.1007/s43207-021-00120-w
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43207-021-00120-w