Recent Trends in Hydroxyapatite (HA) Synthesis and the Synthesis Report of Nanostructure HA by Hydrothermal Reaction

  • Pham Trung KienEmail author
  • Huynh Dai Phu
  • Nguyen Vu Viet Linh
  • Tran Ngoc Quyen
  • Nguyen Thai Hoa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1077)


This research summary the trend in synthesis of Hydroxyapatite (HA) using different route such as dry method and wet method (co-precipitation method; emulsion method, hydrolysis method, sol-gel method, hydrothermal method). In addition, the research group also report the technique to synthesis nano-structure HA by hydrothermal reaction using Ca(OH)2 and H3PO4 with the Ca/P molar ratio of 1.67. The mixture after homogenized for 2 h, follow by hydrothermal reaction at different hydrothermal temperature time (100 °C, 150 °C, and 180 °C) and different hydrothermal reaction time (0 h, 12 h and 24 h). The 180 °C-hydrothermal treated-HA has needle-like shape with the diameter of 10 ~ 20 nm and length of below 100 nm, which is similar with human bone. For the hydrothermal reaction, temperature is the key to form nanostructure HA.


Nano structured hydroxyapatite Hydrothermal reaction Bone substitute Calcium phosphate Biomaterials 



This research is funded by Vietnam National University Ho Chi Minh City (VNU-HCM) under grant number B2015-20a-01. Some of the material characterization facility is supported by National key lab for Polymer and Composite Materials-HCMUT, VAST and HUFI.


  1. 1.
    Driscoll P (2006) Advanced medical technology [Online]. [Accessed 2 Mar 2012]. Available from World Wide Web:
  2. 2.
    Zhao B, Hu H, Mandal SK, Haddon RC (2005) A bone mimic based on the self-assembly of hydroxyapatite on chemically functionalized single-walled carbon nanotubes. Chem Mater 17:3235–3241. CrossRefGoogle Scholar
  3. 3.
    Wagner DE, Eisenmann KM, Nestor-Kalinoski AL, Bhaduri SB (2013) A microwave-assisted solution combustion synthesis to produce europium-doped calcium phosphate nanowhiskers for bioimaging applications. Acta Biomaterialia 9:8422–8432. CrossRefGoogle Scholar
  4. 4.
    Wei X, Yates MZ (2012) Yttrium-doped hydroxyapatite membranes with high proton conductivity. Chem Mater 24:1738–1743. CrossRefGoogle Scholar
  5. 5.
    Watanabe Y, Ikoma T, Suetsugu Y, Yamada H, Tamura K, Komatsu Y, Tanaka J, Moriyoshi Y (2006) The densification of zeolite/apatite composites using a pulse electric current sintering method: a long-term assurance material for the disposal of radioactive waste. J Eur Ceram Soc 26:481–486 CrossRefGoogle Scholar
  6. 6.
    Power AS (1969) Crystal chemistry of bone minerals. Phys Rev 49:760–792. Google Scholar
  7. 7.
    Radin SR, Ducheyne P (1993) The effect of calcium phosphate ceramic composition and structure on in-vitro behavior. J Biomed Mater Res 27:35. CrossRefGoogle Scholar
  8. 8.
    Bett JAS, Christener LG, Hall WK (1967) Hydrogen held by solids XII. Hydroxyapatite catalysts. J Am Chem 89:5535. CrossRefGoogle Scholar
  9. 9.
    Joris SJ, Amberg CH et al (1971) J Phys Chem 75:3167. CrossRefGoogle Scholar
  10. 10.
    Korber F, Trömel GZ (1932) The formation of HA through a solid-state reaction between tri-and tetracalcium phosphates. Electrochem Soc 38:578–580Google Scholar
  11. 11.
    Trömel GZ (1932) Untersuchungen über die Bildung eines halogenfreien Apatits aus basischen Calciumphosphaten. Physik Chem 158:422–432. Google Scholar
  12. 12.
    Ikoma T, Yamazaki A, Nakamura S, Akao M (1999) Preparation and structure refinement of monoclinic hydroxyapatite. J Solid State Chem 144:272–276. CrossRefGoogle Scholar
  13. 13.
    Tao J, Jiang W, Pan H, Xu X, Tang R (2007) Preparation of large-sized hydroxyapatite single crystals using homogeneous releasing controls. J Cryst Growth 308:151–158. CrossRefGoogle Scholar
  14. 14.
    Zhang Y, Lu J (2008) A mild and efficient biomimetic synthesis of rodlike hydroxyapatite particles with a high aspect ratio using polyvinylpyrrolidone as capping agent. Cryst Growth Des 8:2101–2107. CrossRefGoogle Scholar
  15. 15.
    Shum HC, Bandyopadhyay A, Bose S, Weitz DA (2009) Double emulsion droplets as microreactors for synthesis of mesoporous hydroxyapatite. Chem Mater 21:5548–5555. CrossRefGoogle Scholar
  16. 16.
    Zhou W, Wang M, Cheung W, Guo B, Jia D (2008) Synthesis of carbonated hydroxyapatite nanospheres through nanoemulsion. J Mater Sci Mater Med 19:103–110. CrossRefGoogle Scholar
  17. 17.
    Ethirajan A, Ziener U, Chuvilin A, Kaiser U, Cölfen H, Landfester K (2008) Biomimetic hydroxyapatite crystallization in gelatin nanoparticles synthesized using a miniemulsion process. Adv Funct Mater 18:2221–2227. CrossRefGoogle Scholar
  18. 18.
    Sturgeon JL, Brown PW (2009) Effects of carbonate on hydroxyapatite formed from CaHPO4 and Ca4(PO4)2O. J Mater Sci Mater Med 20:1787–1794. CrossRefGoogle Scholar
  19. 19.
    Park H, Baek D, Park Y, Yoon S, Stevens R (2004) Thermal stability of hydroxyapatite whiskers derived from the hydrolysis of α-TCP. J Mater Sci 39:2531–2534CrossRefGoogle Scholar
  20. 20.
    Sakamoto K, Yamaguchi S, Nakahira A, Kaneno M, Okazaki M, Ichihara J, Tsunawaki Y, Elliott JC (2002) Shape-controlled synthesis of hydroxyapatite from α-tricalcium bis(orthophosphate) in organic-aqueous binary systems. J Mater Sci 37:1033–1041CrossRefGoogle Scholar
  21. 21.
    Durucan C, Brown PA (2000) α-Tricalcium phosphate hydrolysis to hydroxyapatite at and near physiological temperature. J Mater Sci Mater Med 11:365–371CrossRefGoogle Scholar
  22. 22.
    Graham S, Brown PW (1996) Reactions of octacalcium phosphate to form hydroxyapatite. J Cryst Growth 165:106–115. CrossRefGoogle Scholar
  23. 23.
    De Maeyer EAP, Verbeeck RMH, Pieters IY (1996) Effect of K+ on the stoichiometry of carbonated hydroxyapatite obtained by the jydrolysis of monetite. Inorg Chem 35:857–863. CrossRefGoogle Scholar
  24. 24.
    Kim I, Kumta PN (2004) Sol–gel synthesis and characterization of nanostructured hydroxyapatite powder. Mater Sci Eng B 111:232–236. CrossRefGoogle Scholar
  25. 25.
    Feng W, Mu-Sen L, Yu-Peng L, Yong-Xin Q (2005) A simple sol–gel technique for preparing hydroxyapatite nanopowders. Mater Lett 59:916–919. CrossRefGoogle Scholar
  26. 26.
    Rajabi-Zamani AH, Behnamghader A, Kazemzadeh A (2008) Synthesis of nanocrystalline carbonated hydroxyapatite powder via nonalkoxide sol–gel method. Mater Sci Eng C 28:1326–1329. CrossRefGoogle Scholar
  27. 27.
    Hsieh MF, Perng LH, Chin TS, Perng HG (2001) Phase purity of sol–gel-derived hydroxyapatite ceramic. Biomaterials 22:2601–2607. CrossRefGoogle Scholar
  28. 28.
    Eshtiagh-Hosseini H, Housaindokht MR, Chahkandi M (2007) Effects of parameters of sol–gel process on the phase evolution of sol–gel-derived hydroxyapatite. Mater Chem Phys 106:310–316. CrossRefGoogle Scholar
  29. 29.
    Chen J, Wang Y, Chen X, Ren L, Lai C, He W, Zhang Q (2011) A simple sol-gel technique for synthesis of nanostructured hydroxyapatite, tricalcium phosphate and biphasic powders. Mater Lett 65:1923–1926. CrossRefGoogle Scholar
  30. 30.
    Velu G, Gopal B (2009) Preparation of nanohydroxyapatite by a sol–gel method using alginic acid as a complexing agent. J Am Ceram Soc 92:2207–2211. CrossRefGoogle Scholar
  31. 31.
    Zhang H, Zhang M (2011) Phase and thermal stability of hydroxyapatite whiskers precipitated using amine additives. Ceram Int 37:279–286. CrossRefGoogle Scholar
  32. 32.
    Guo X, Xiao P, Liu J, Shen Z (2005) Fabrication of nanostructured hydroxyapatite via hydrothermal synthesis and spark plasma sintering. J Am Ceram Soc 88:1026–1029. CrossRefGoogle Scholar
  33. 33.
    Tsiourvas D, Tsetsekou A, Kammenou MI, Boukos N (2011) Controlling the formation of hydroxyapatite nanorods with dendrimers. J Am Ceram Soc 94:2023–2029. CrossRefGoogle Scholar
  34. 34.
    Zhang H, Darvell BW (2011) Biomaterials 7:2960–2968Google Scholar
  35. 35.
    Lin K, Liu X, Chang J, Zhu Y (2011) Facile synthesis of hydroxyapatite nanoparticles, nanowires and hollow nano-structured microspheres using similar structured hard-precursors. Nanoscale 3:3052–3055. CrossRefGoogle Scholar
  36. 36.
    Lee DK, Park JY, Kim MR, Jang DJ (2011) Facile hydrothermal fabrication of hollow hexagonal hydroxyapatite prisms. CrystEngComm 13:5455–5459. CrossRefGoogle Scholar
  37. 37.
    Zhu K, Yanagisawa K, Onda A, Kajiyoshi K, Qiu J (2009) Morphology variation of cadmium hydroxyapatite synthesized by high temperature mixing method under hydrothermal conditions. Mater Chem Phys 113:239–243. CrossRefGoogle Scholar
  38. 38.
    Cao H, Zhang L, Zheng H, Wang Z (2010) Hydroxyapatite nanocrystals for biomedical applications. J Phys Chem C 114:18352–18357. CrossRefGoogle Scholar
  39. 39.
    Zhang G, Chen J, Yang S, Yu Q, Wang Z, Zhang Q (2011) Preparation of amino-acid-regulated hydroxyapatite particles by hydrothermal method. Mater Lett 65:572–574. CrossRefGoogle Scholar
  40. 40.
    Pham Trung Kien, Tsuru Kanji, Kunio Ishikawa (2015) Development and characterization of porous calcium phosphate cement using α-tricalcium phosphate bead. In: Vo Van Toi, Tran Ha Lien Phuong (eds) 5th international conference on biomedical engineering in Vietnam. IFMBE proceedings, pp 507–510.
  41. 41.
    Nguyen Viet Long, Masayuki Nogami, Yong Yang, Michitaka Ohtaki, Pham TrungKien, Cao Minh Thi (2014) Magnetic metal and oxide based nanoparticles and biomaterials for bioimaging probes for magnetic resonance imaging, Chapter 6. In: Govil JN (ed) Nanotechnology, Volume 12: bioimaging. Studium Press LLC, pp 205–221Google Scholar
  42. 42.
    Pham Trung Kien, Vang Nguyen Hoang Van, Tran Pham Quang Nguyen, Pham Thi Lan Thanh (2018) Evaluation effect of stirring mode on synthesize Hydroxyapatite crystallite used as bone substitute. In: The 6th international conference on biomedical engineering in Vietnam, Ho Chi Minh City, Vietnam, pp 331–334Google Scholar
  43. 43.
    Pham Trung Kien, Tsuru Kanji, Kunio Ishikawa (2015) Setting reaction of α-TCP spheres and an acidic calcium phosphate solution for the fabrication of fully interconnected macroporous calcium phosphate. Ceram Int 41:13525–13531. CrossRefGoogle Scholar
  44. 44.
    Kien Pham Trung, Minh Do Quang, Thanh Pham ThiLan (2014) Iron-free hydroxyapatite powder from synthetic Ca(OH)2 and commercialized Ca(OH)2. Adv Mater Res 858:103–110CrossRefGoogle Scholar
  45. 45.
    Kunio Ishikawa, Kanji Tsuru, Trung Kien Pham, Michito Maruta, Shigeki Matsuya (2012) Fully-interconnected pore forming calcium phosphate cement. Key Eng Mater 493–494:832–835Google Scholar
  46. 46.
    Pham Trung Kien, Michito Maruta, Kanji Tsuru, Shigeki Matsuya, Kunio Ishikawa (2010) Effect of phosphate solution on setting reaction of α-TCP spheres. J Aust Ceram Soc 46(2):63–67Google Scholar
  47. 47.
    Radzali Othman, Ahmad Fauzi, Pham Trung Kien, Kunio Ishikawa, Do Quang Minh (2007) Preparation and characterization of β-tricalcium phosphate. Malaysia J Microsc 3:193–198Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Pham Trung Kien
    • 1
    Email author
  • Huynh Dai Phu
    • 1
    • 2
  • Nguyen Vu Viet Linh
    • 1
    • 2
  • Tran Ngoc Quyen
    • 3
  • Nguyen Thai Hoa
    • 4
  1. 1.Faculty of Materials TechnologyHo Chi Minh City University of Technology (HCMUT), Vietnam National University (VNU-HCM)Ho Chi Minh CityVietnam
  2. 2.National Key Lab for Polymer and Composite MaterialsHCMUTHo Chi Minh CityVietnam
  3. 3.Graduate School of Science and Technology, Department of Pharmacy and MedicineVietnam Academy of Science and TechnologyHo Chi Minh CityVietnam
  4. 4.Key Lab for Materials TechnologyHo Chi Minh City University of TechnologyHo Chi Minh CityVietnam

Personalised recommendations