Addition of sodium hyaluronate and the effect on performance of the injectable calcium phosphate cement

  • Dan Kai
  • Dongxiao Li
  • Xiangdong Zhu
  • Lei Zhang
  • Hongsong Fan
  • Xingdong Zhang


An injectable calcium phosphate cement (CPC) with porous structure and excellent anti-washout ability was developed in the study. Citric acid and sodium bicarbonate were added into the CPC powder consisting of tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD) to form macro-pores, then different concentrations of sodium hyaluronate (NaHA) solution, as liquid phase, was added into the cement to investigate its effect on CPC’s performance. The prepared CPCs were tested on workability (injectable time and setting time), mechanical strength, as well as anti-washout ability. The experimental results showed that addition of NaHA not only enhanced the anti-washout ability of the CPC dramatically but also improve its other properties. When NaHA concentration was 0.6 wt%, the injectable time elongated to 15.7 ± 0.6 min, the initial and final setting times were respectively shorten to 18.3 ± 1.2 and 58.7 ± 2.1 min, and the compressive strength were increased to 18.78 ± 1.83 MPa. On the other hand, Addition of NaHA showed little effect on porous structure of the CPC and enhanced its bioactivity obviously, which was confirmed by the apatite formation on its surface after immersion in simulated body fluid (SBF). In conclusion, as an in situ shaped injectable biomaterials, the CPC with appropriate addition of NaHA would notably improve its performance and might be used in minimal invasive surgery for bone repair or reconstruction.


Compressive Strength Hyaluronate Simulated Body Fluid Minimal Invasive Surgery Calcium Phosphate Cement 
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  1. 1.
    Takagi S, Chow LC, Ishikawa K. Formation of hydroxyapatite in new calcium phosphate cements. Biomaterials. 1998;19(17):1593–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Ginebra MP, Traykova T, Planell JA. Calcium phosphate cements as bone drug delivery systems: a review. Journal Control Release. 2006;113(2):102–10.CrossRefGoogle Scholar
  3. 3.
    Habraken W, de Jonge LT, Wolke JGC, Yubao L, Mikos AG, Jansen JA. Introduction of gelatin microspheres into an injectable calcium phosphate cement. J Biomed Mater Res A. 2008;87A(3):643–55.CrossRefGoogle Scholar
  4. 4.
    Comuzzi L, Ooms E, Jansen JA. Injectable calcium phosphate cement as a filler for bone defects around oral implants: an experimental study in goats. Clin Oral Implant Res. 2002;13(3):304–11.CrossRefGoogle Scholar
  5. 5.
    Tamimi F, Torres J, Lopez-Cabarcos E, Bassett DC, Habibovic P, Luceron E, et al. Minimally invasive maxillofacial vertical bone augmentation using brushite based cements. Biomaterials. 2009;30(2):208–16.PubMedCrossRefGoogle Scholar
  6. 6.
    Burguera EF, Xu HHK, Weir MD. Injectable and rapid-setting calcium phosphate bone cement with dicalcium phosphate dihydrate. J Biomed Mater Res B-Appl Biomater. 2006;77B(1):126–34.CrossRefGoogle Scholar
  7. 7.
    Liu H, Li H, Cheng WJ, Yang Y, Zhu MY, Zhou CR. Novel injectable calcium phosphate/chitosan composites for bone substitute materials. Acta Biomater. 2006;2(5):557–65.PubMedCrossRefGoogle Scholar
  8. 8.
    Xu H, Simon CG. Self-hardening calcium phosphate composite scaffold for bone tissue engineering. J Orthop Res. 2004;22(3):535–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang XP, Ye JD, Wang YJ, Wu XP, Bai B. Control of crystallinity of hydrated products in a calcium phosphate bone cement. J Biomed Mater Res A. 2007;81A(4):781–90.CrossRefGoogle Scholar
  10. 10.
    Xu HHK, Burguera EF, Carey LE. Strong, macroporous, and in situ-setting calcium phosphate cement-layered structures. Biomaterials. 2007;28(26):3786–96.PubMedCrossRefGoogle Scholar
  11. 11.
    Wang XP, Ye J, Wang YJ. Influence of a novel radiopacifier on the properties of an injectable calcium phosphate cement. Acta Biomater. 2007;3(5):757–63.PubMedCrossRefMathSciNetGoogle Scholar
  12. 12.
    Tien YC, Chih TT, Lin JHC, Ju CP, Lin SD. Augmentation of tendon-bone healing by the use of calcium-phosphate cement. J Bone Joint Surg Br. 2004;86B(7):1072–6.CrossRefGoogle Scholar
  13. 13.
    Leroux L, Hatim Z, Freche M, Lacout JL. Effects of various adjuvants (lactic acid, glycerol, and chitosan) on the injectability of a calcium phosphate cement. 9th European Meeting on Injectable Bone and Joint Substitution Materials; 1999 Mar 01–02; Lausanne, Switzerland; 1999. p. 31S–34S.Google Scholar
  14. 14.
    Khairoun I, Boltong MG, Driessens FCM, Planell JA. Effect of calcium carbonate on clinical compliance of apatitic calcium phosphate bone cement. J Biomed Mater Res. 1997;38(4):356–60.PubMedCrossRefGoogle Scholar
  15. 15.
    Takagi S, Chow LC, Hirayama S, Sugawara A. Premixed calcium-phosphate cement pastes. J Biomed Mater Res B-Appl Biomater. 2003;67B(2):689–96.CrossRefGoogle Scholar
  16. 16.
    Shie MY, Chen DCH, Wang CY, Chiang TY, Ding SJ. Immersion behavior of gelatin-containing calcium phosphate cement. Acta Biomater. 2008;4(3):646–55.PubMedCrossRefGoogle Scholar
  17. 17.
    Wang XP, Chen L, Xiang H, Ye JD. Influence of anti-washout agents on the rheological properties and injectability of a calcium phosphate cement. J Biomed Mater Res B-Appl Biomater. 2007;81B(2):410–8.CrossRefGoogle Scholar
  18. 18.
    Watanab M, Tanaka M, Sakurai M, Maeda M. Development of calcium phosphate cement. J Eur Ceram Soc. 2006;26:549–52.CrossRefGoogle Scholar
  19. 19.
    Sarda S, Fernandez E, Nilsson M, Balcells M, Planell JA. Kinetic study of citric acid influence on calcium phosphate bone cements as water-reducing agent. J Biomed Mater Res. 2002;61(4):653–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Khairoun I, Driessens FCM, Boltong MG, Planell JA, Wenz R. Addition of cohesion promoters to calcium phosphate cements. Biomaterials. 1999;20(4):393–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Rau JV, Generosi A, Smirnov VV, Ferro D, Albertini VR, Barinov SM. Energy dispersive X-ray diffraction study of phase development during hardening of calcium phosphate bone cements with addition of chitosan. Acta Biomater. 2008;4(4):1089–94.PubMedCrossRefGoogle Scholar
  22. 22.
    Almond A, DeAngelis PL, Blundell CD. Hyaluronan: The local solution conformation determined by NMR and computer modeling is close to a contracted left-handed 4-fold helix. J Mol Biol. 2006;358(5):1256–69.PubMedCrossRefGoogle Scholar
  23. 23.
    Shin DY, Hwang E, Cho IH, Moon MH. Molecular weight and structure characterization of sodium hyaluronate and its gamma radiation degradation products by flow field-flow fractionation and on-line multiangle light scattering. J Chromatogr A. 2007;1160(1–2):270–5.CrossRefGoogle Scholar
  24. 24.
    Brown MB, Jones SA. Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin. J Eur Acad Dermatol Venereol. 2005;19(3):308–18.PubMedCrossRefGoogle Scholar
  25. 25.
    Li DX, Fan HS, Zhu XD, Tan YF, Xiao WQ, Lu J, et al. Controllable release of salmon-calcitonin in injectable calcium phosphate cement modified by chitosan oligosaccharide and collagen polypeptide. J Mater Sci Mater Med. 2007;18(11):2225–31.PubMedCrossRefGoogle Scholar
  26. 26.
    Kokubo T, Takadama H. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials. 2006;27(15):2907–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Xu HHK, Weir MD, Burguera EF, Fraser AM. Injectable and macroporous calcium phosphate cement scaffold. Biomaterials. 2006;27(24):4279–87.PubMedCrossRefGoogle Scholar
  28. 28.
    Kondo N, Ogose A, Tokunaga K, Umezu H, Arai K, Kudo N, et al. Osteoinduction with highly purified beta-tricalcium phosphate in dog dorsal muscles and the proliferation of osteoclasts before heterotopic bone formation. Biomaterials. 2006;27(25):4419–27.PubMedCrossRefGoogle Scholar
  29. 29.
    Zaffe D. Some considerations on biomaterials and bone. Micron. 2005;36(7–8):583–92.PubMedCrossRefGoogle Scholar
  30. 30.
    Link DP, Van den Dolder J, Van den Beucken J, Cuijpers VM, Wolke JGC, Mikos AG, et al. Evaluation of the biocompatibility of calcium phosphate cement/PLGA microparticle composites. J Biomed Mater Res A. 2008;87A(3):760–9.CrossRefGoogle Scholar
  31. 31.
    Habibovic P, Gbureck U, Doillon CJ, Bassett DC, van Blitterswijk CA, Barralet JE. Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic implants. Biomaterials. 2008;29(7):944–53.PubMedCrossRefGoogle Scholar
  32. 32.
    Generosi A, Smimov VV, Rau JV, Albertini VR, Ferro D, Barinov SM. Phase development in the hardening process of two calcium phosphate bone cements: An energy dispersive X-ray diffraction study. Mater Res Bull. 2008;43(3):561–71.CrossRefGoogle Scholar
  33. 33.
    Han Y, Li H, Zhou C, Rong J. Experimental studies on calcium phosphate bone cement containing carboxymethyl chitosan. J Jinan Univ (Natural Science). 2007;28:288–91.Google Scholar
  34. 34.
    Napier MA, Hadler NM. Effect of calcium on structure and function of a hyaluronic acid matrix: Carbon-13 nuclear magnetic resonance analysis and the diffusional behavior of small solutes. Biochemitry. 1978;75:2261–5.Google Scholar
  35. 35.
    Furth G, Knierim R, Buss V, Mayer C. Binding of bivalent cations by hyaluronate in aqueous solution. Int J Biol Macromol. 2008;42(1):33–40.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Dan Kai
    • 1
  • Dongxiao Li
    • 2
  • Xiangdong Zhu
    • 1
  • Lei Zhang
    • 2
  • Hongsong Fan
    • 1
  • Xingdong Zhang
    • 1
  1. 1.National Engineering Research Center for BiomaterialsSichuan UniversityChengduChina
  2. 2.Institute of Pharmacology & ToxicologySichuan Academy of Chinese Medicine ScienceChengduChina

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