Journal of Materials Science: Materials in Medicine

, Volume 19, Issue 12, pp 3575–3583

Injectable iron-modified apatitic bone cement intended for kyphoplasty: cytocompatibility study

  • M. D. Vlad
  • L. J. del Valle
  • I. Poeata
  • M. Barracó
  • J. López
  • R. Torres
  • E. Fernández


In this study, the cytocompatibility of human ephitelial (HEp-2) cells cultured on new injectable iron-modified calcium phosphate cements (IM-CPCs) has been investigated in terms of cell adhesion, cell proliferation, and morphology. Quantitative MTT-assay and scanning electron microscopy (SEM) showed that cell adhesion and viability were not affected with culturing time by iron concentration in a dose-dependent manner. SEM-cell morphology showed that HEp-2 cells, seeded on IM-CPCs, were able to adhere, spread, and attain normal morphology. These results showed that the new injectable IM-CPCs have cytocompatible features of interest to the intended kyphophasty application, for the treatment of osteoporotic vertebral compression fractures.


  1. 1.
    K. Takegami, T. Sano, H. Wakabayashi, J. Sonoda, T. Yamazaki, S. Morita, T. Shibuya, A. Uchida, New ferromagnetic bone cement for local hyperthermia. J. Biomed. Mater. Res. Part B Appl. Biomater. 43B, 210–214 (1998)CrossRefGoogle Scholar
  2. 2.
    D. Arcos, R.P. del Real, M. Vallet-Regi, Biphasic materials for bone grafting and hyperthermia treatment of cancer. J. Biomed. Mater. Res. 65A, 71–78 (2003)CrossRefGoogle Scholar
  3. 3.
    M. Kawashita, S. Domi, Y. Saito, M. Aoki, Y. Ebisawa, T. Kokubo, T. Saito, M. Takano, N. Araki, M. Hiraoka, In vitro heat generation by ferromagnetic maghemite microspheres for hyperthermia treatment of cancer under an alternating magnetic field. J. Mater. Sci.: Mater. Med. 19, 1897–1903 (2008)CrossRefGoogle Scholar
  4. 4.
    C.C. Berry, S. Wells, S. Charles, A.S.G. Curtis, Dextran and albumin derivatised iron oxide nanoparticles: influence on fibroblast in vitro. Biomaterials 24, 4551–4557 (2003)CrossRefGoogle Scholar
  5. 5.
    E.H. Kim, H.S. Lee, B.K. Kwak, B.K. Kim, Synthesis of ferrofluid with magnetic nanoparticles by sonochemical method for MRI contrast agent. J. Magn. Magn. Mater. 289, 328–330 (2005)CrossRefGoogle Scholar
  6. 6.
    O. Kakhlon, Z.I. Cabantchik, The labile iron pool: characterisation, measurement, and participation in cellular processes. Free Radic. Biol. Med. 33(8), 1037–1046 (2002)CrossRefGoogle Scholar
  7. 7.
    M.W. Henze, M.U. Muckenthaler, N.C. Andrews, Balancing acts: molecular control of mamalian iron metabolism. Cell 117, 285–297 (2004)CrossRefGoogle Scholar
  8. 8.
    R. Cotran, V. Kumar, A.K. Abbas, N. Fausto, in Pathologic Basis of Disease, ed. by Robbins & Cotran, Chapt 1, 7th edn. (WB Saunders Co., 2004), pp. 14–17Google Scholar
  9. 9.
    S.V. Dorozhkin, Calcium orthophosphate cements for biomedical application. J. Mater. Sci. 43, 3028–3057 (2008)CrossRefGoogle Scholar
  10. 10.
    E. Fernández, F.J. Gil, S.M. Best, M.P. Ginebra, F.C.M. Driessens, J.A. Planell, Improvement of the mechanical properties of new calcium phosphate bone cements in the CaHPO4-α-Ca3(PO4)2 system: compressive strength and microstructural development. J. Biomed. Mater. Res. 41, 560–67 (1998)CrossRefGoogle Scholar
  11. 11.
    E. Fernández , Bioactive Bone Cements. in Wiley Encyclopedia of Biomedical Engineering, 6-Volume Set. ed. by M. Akay. (Wiley, USA, 2006), pp. 1–9Google Scholar
  12. 12.
    A. Gisep, R. Wieling, M. Bohner, S. Matter, E. Schneider, B. Rahn, Resorption patterns of calcium-phosphate cements in bone. J. Biomed. Mater. Res. 66(3), 532–540 (2003)CrossRefGoogle Scholar
  13. 13.
    D. Apelt, F. Theiss, A.O. El-Warrak, K. Zlinszky, R.B. Wolfisberger, M. Bohner, S. Matter, J.A. Auer, B. von Rechenberg, In vitro behavior of three different injectable hydraulic calcium phosphate cements. Biomaterials 25, 1439–1451 (2004)CrossRefGoogle Scholar
  14. 14.
    M. Bohner, Physical and chemical aspects of calcium phosphates used in spinal surgery. Eur. Spine. J. 10, S114–S121 (2001)CrossRefGoogle Scholar
  15. 15.
    S. Deb, J. Giri, S. Dasgupta, D. Datta, D. Bahadur, Synthesis and characterisation of biocompatible hydroxyapatite coated ferrite. Bull. Mater. Sci. 26(7), 655–660 (2003)CrossRefGoogle Scholar
  16. 16.
    D. Arcos, R.P. del Real, M. Vallet-Regi, A novel bioactive and magnetic biphasic material. Biomaterials 23, 2151–2158 (2002)CrossRefGoogle Scholar
  17. 17.
    M. Tyllianakis, D. Giannikas, A. Panagopoulos, E. Panagiotopoulos, E. Lambiris, Use of injectable calcium phosphate in the treatment of intra-articular distal radius fractures. Orthopedics 25(3), 311–315 (2002)Google Scholar
  18. 18.
    M. Bohner, U. Gbureck, J.E. Barralet, Technological issues for the development of more efficient calcium phosphate bone cements: a critical assessment. Biomaterials 26, 6423–6429 (2005)CrossRefGoogle Scholar
  19. 19.
    G. Lewis, Percutaneous vertebroplaty and kyphoplasty for the stand-alone augmentation of osteoporosis-induced vertebral compression fractures: present status and future directions. J. Biomed. Mater. Res. Part B: Appl. Biomater. 81B, 371–386 (2007)CrossRefGoogle Scholar
  20. 20.
    G. Lewis, Injectable bone cements for use in vertebroplasty and kyphoplasty: state of the art review. J. Biomed. Mater. Res. Part B: Appl. Biomater. 76B, 456–468 (2006)CrossRefGoogle Scholar
  21. 21.
    E. Fernández, M.D. Vlad, M. Hamcerencu, A. Darie, R. Torres, J. López, Effect of iron on the setting properties of α-TCP bone cements. J. Mater. Sci. 40, 3677–3682 (2005)CrossRefGoogle Scholar
  22. 22.
    M.D. Vlad, L.J. del Valle, M. Barracó, R. Torres, J. López, E. Fernández, Iron oxide nanoparticles significantly enhances the injectability of apatitic bone cement for vertebroplasty. Spine, (2008) (Accepted)Google Scholar
  23. 23.
    E. Fernández, M.D. Vlad, M.M. Gel, J. López, R. Torres, J.V. Cauich, M. Bohner, Modulation of porosity in apatitic cements by the use of α-tricalcium phosphate–calcium sulphate dehydrate mixtures. Biomaterials 26, 3395–3404 (2005)CrossRefGoogle Scholar
  24. 24.
    M. Jiang, J. Terra, A.M. Rossi, M.A. Morales, E.M.B. Saitovitch, D.E. Ellis, Fe2+/Fe3+ substitution in hydroxyapatite: Theory and experiment. Phys. Rev. B 66(22), 224107-1–224107-15 (2002)CrossRefGoogle Scholar
  25. 25.
    E. Fernández, M.P. Ginebra, M.G. Boltong, F.C.M. Driessens, J.A. Planell, J. Ginebra, E.A.P. De Maeyer, R.M.H. Verbeeck, Kinetic study of the setting reaction of calcium phosphate bone cements. J. Biomed. Mater. Res. 32, 367–374 (1996)CrossRefGoogle Scholar
  26. 26.
    K. Anselme, M. Bigerelle, B. Noel, E. Dufresne, D. Judas, A. Iost, P. Hardouin, Qualitative and quantitative of human osteoblast adhesion on materials with various surface roughness. J. Biomed. Mater. Res. 49, 155–66 (2000)CrossRefGoogle Scholar
  27. 27.
    N. Ignjatovic, P. Ninkov, V. Kojic, M. Bokurov, V. Srdic, D. Krnojelac, S. Selakovic, D. Uskokovic, Cytotoxicity and fibroblast properties during in vitro test of biphasic calcium phosphate/poly-di-lactide-co-glycolide biocomposites and different phosphate materials. Microsc. Res. Tech. 69, 976–982 (2006)CrossRefGoogle Scholar
  28. 28.
    T. Suzuki, R. Ohashi, Y. Yokogawa, K. Nishizawa, F. Nagata, Y. Kawamoto, T. Kameyama, M. Toriyama, Initial anchoring and proliferation of fibroblast L-929 cells on unstable surface of calcium phosphate ceramics. J. Biosci. Bioeng. 87(3), 320–327 (1999)CrossRefGoogle Scholar
  29. 29.
    C.G. Simon, W.F. Guthrie, F.W. Wang, Cell seeding into calcium phosphate cement. J. Biomed. Mater. Res. 68A, 628–639 (2004)CrossRefGoogle Scholar
  30. 30.
    P. Juin, M. Pelletier, L. Oliver, K. Tremblais, M. Gregoire, K. Meflah, F.M. Vallette, Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. J. Biol. Chem. 273(28), 17559–17564 (1998)CrossRefGoogle Scholar
  31. 31.
    B. Qualmann, M.M. Kessels, R.B. Kelly, Molecular links between endocytosis and the actin cytoskeleton. J. Cell Biol. 150(5), F111–F116 (2000)CrossRefGoogle Scholar
  32. 32.
    C.S. Chen, M. Mrksich, S. Huang, G.M. Whitesides, D.E. Ingber, Geometric control of cell life and death. Science 276, 1425–1428 (1997)CrossRefGoogle Scholar
  33. 33.
    J.T. Ninomiya, J.A. Struve, C.T. Stelloh, J.M. Toth, K.E. Crosby, Effects of hydroxyapatite particulate debris on the production of cytokines and proteases in human fibroblasts. J. Orthop. Res. 19, 621–628 (2001)CrossRefGoogle Scholar
  34. 34.
    D.P. Pioletti, H. Takei, T. Lin, P. Van Landuyt, Q.J. Ma, S.Y. Kwon, K.L.P. Sung, The effects of calcium phosphate cement particles on osteoblast functions. Biomaterials 21, 1103–1114 (2000)CrossRefGoogle Scholar
  35. 35.
    K. Anselme, Osteoblast adhesion on biomaterials. Biomaterials 21, 667–681 (2000)CrossRefGoogle Scholar
  36. 36.
    C.C. Berry, G. Campbell, A. Spadiccino, M. Robertson, A.S.G. Curtis, The influence of microscale topography on fibroblast attachment and mobility. Biomaterials 25, 5781–5788 (2004)CrossRefGoogle Scholar
  37. 37.
    E.M. Harnett, J. Alderman, T. Wood, The surface energy of various biomaterials coated with adhesion molecules used in cell culture. Colloids Surf. B Biointerfaces 55, 90–97 (2007)CrossRefGoogle Scholar
  38. 38.
    T. Yoshida, E. Yoshimura, H. Numata, Y. Sakakura, T. Sakakura, Involvement of tenascin-C in proliferation and migration of laryngeal carcinoma cells. Virchows Archiv. 435, 496–500 (1999)CrossRefGoogle Scholar
  39. 39.
    B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter (ed.), Molecular Biology of the cell, 4th edn. (Garland Science, NY, 2002), pp. 907–1080Google Scholar
  40. 40.
    B. Safiejko-Mroczka, P.B. Bell, Reorganization of the actin cytoscheleton in the protruding lamellae of human fibroblasts. Cell Motil. Cytoskeleton 50, 13–32 (2001)CrossRefGoogle Scholar
  41. 41.
    H. Lefaix, A. Asselin, P. Vermaut, J.M. Sautier, A. Berdal, R. Portier, F. Prima, On the biocompatibility of a novel Ti-based amorphouos composite: structural characterisation and in vitro osteoblasts response. J. Mater. Sci.: Mater. Med. 19, 1861–1869 (2008)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • M. D. Vlad
    • 1
    • 2
  • L. J. del Valle
    • 3
  • I. Poeata
    • 2
  • M. Barracó
    • 1
  • J. López
    • 1
  • R. Torres
    • 1
  • E. Fernández
    • 1
  1. 1.Division of Biomaterials & Bioengineering, Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC)Technical University of Catalonia (UPC)BarcelonaSpain
  2. 2.Faculty of Medical BioengineeringUniversity of Medicine and Pharmacy “Gr. T. Popa”IasiRomania
  3. 3.Department of Agri-Food Engineering and Biotechnology (DEAB), ESABUPCCastelldefelsSpain

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