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The stability mechanisms of an injectable calcium phosphate ceramic suspension

  • Ahmed Fatimi
  • Jean-François Tassin
  • Monique A. V. Axelos
  • Pierre Weiss
Article

Abstract

Calcium phosphate ceramics are widely used as bone substitutes in dentistry and orthopedic applications. For minimally invasive surgery an injectable calcium phosphate ceramic suspension (ICPCS) was developed. It consists in a biopolymer (hydroxypropylmethylcellulose: HPMC) as matrix and bioactive calcium phosphate ceramics (biphasic calcium phosphate: BCP) as fillers. The stability of the suspension is essential to this generation of “ready to use” injectable biomaterial. But, during storage, the particles settle down. The engineering sciences have long been interested in models describing the settling (or sedimentation) of particles in viscous fluids. Our work is dedicated to the comprehension of the effect of the formulation on the stability of calcium phosphate suspension before and after steam sterilization. The rheological characterization revealed the macromolecular behavior of the suspending medium. The investigations of settling kinetics showed the influence of the BCP particle size and the HPMC concentration on the settling velocity and sediment compactness before and after sterilization. To decrease the sedimentation process, the granule size has to be smaller and the polymer concentration has to increase. A much lower sedimentation velocity, as compared to Stokes law, is observed and interpreted in terms of interactions between the polymer network in solution and the particles. This experimentation highlights the granules spacer property of hydrophilic macromolecules that is a key issue for interconnection control, one of the better ways to improve osteoconduction and bioactivity.

Keywords

Calcium Phosphate Sedimentation Velocity Biphasic Calcium Phosphate Sediment Volume Newtonian Viscosity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This present work was supported by the regional program BIOREGOS (Région Pays de la Loire, France). The help of Paul Pilet (LIOAD INSERM U791, Nantes) for the SEM analysis, Jean-Michel Bouler (LIOAD INSERM U791, Nantes) for BCP preparation, and Stephane Grolleau (CNRS IMN, Nantes) for density measurements is acknowledged with gratitude. We thank Colorcon® for providing the Methocel™ E4M.

References

  1. 1.
    Gauthier O, Bouler JM, Aguado E, Pilet P, Daculsi G. Macroporous biphasic calcium phosphate ceramics: influence of macropore diameter and macroporosity percentage on bone ingrowth. Biomaterials. 1998;19(1–3):133–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Weiss P, Layrolle P, Clergeau LP, Enckel B, Pilet P, Amouriq Y, et al. The safety and efficacy of an injectable bone substitute in dental sockets demonstrated in a human clinical trial. Biomaterials. 2007;28(22):3295–305.CrossRefPubMedGoogle Scholar
  3. 3.
    Klein CP, van der Lubbe HB, de Groot K. A plastic composite of alginate with calcium phosphate granulate as implant material: an in vivo study. Biomaterials. 1987;8(4):308–10.PubMedGoogle Scholar
  4. 4.
    Fatimi A, Tassin JF, Quillard S, Axelos MAV, Weiss P. The rheological properties of silated hydroxypropylmethylcellulose tissue engineering matrices. Biomaterials. 2008;29(5):533–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Chazono M, Tanaka T, Komaki H, Fujii K. Bone formation and bioresorption after implantation of injectable beta-tricalcium phosphate granules–hyaluronate complex in rabbit bone defects. J Biomed Mater Res Part A. 2004;70A(4):542–9.CrossRefGoogle Scholar
  6. 6.
    Barros RR, Novaes AB Jr, Roriz VM, Oliveira RR, Grisi MF, Souza SL, et al. Anorganic bovine matrix/p-15 “flow” in the treatment of periodontal defects: case series with 12 months of follow-up. J Periodontol. 2006;77(7):1280–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Shojaei A, Arefinia R. Analysis of the sedimentation process in reactive polymeric suspensions. Chem Eng Sci. 2006;61(23):7565–78.CrossRefGoogle Scholar
  8. 8.
    Balastre M, Argillier JF, Allain C, Foissy A. Role of polyelectrolyte dispersant in the settling behaviour of barium sulphate suspension. Colloids Surf A Physicochem Eng Asp. 2002;211(2–3):145–56.CrossRefGoogle Scholar
  9. 9.
    Novales B, Papineau P, Sire A, Axelos MAV. Characterization of emulsions and suspensions by video image analysis. Colloids Surf A Physicochem Eng Asp. 2003;221(1–3):81–9.CrossRefGoogle Scholar
  10. 10.
    Gallardo V, Morales ME, Ruiz MA, Delgado AV. An experimental investigation of the stability of ethylcellulose latex: correlation between zeta potential and sedimentation. Eur J Pharm Sci. 2005;26(2):170–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Kynch GJ. A theory of sedimentation. Trans Faraday Soc. 1952;48:166–76.CrossRefGoogle Scholar
  12. 12.
    Davis KE, Russel WB. An asymptotic description of transient settling and ultrafiltration of colloidal dispersions. Phys Fluids A: Fluid Dyn. 1989;1(1):82–100.CrossRefADSGoogle Scholar
  13. 13.
    Allain C, Cloitre M, Wafra M. Aggregation and sedimentation in colloidal suspensions. Phys Rev Lett. 1995;74(8):1478–81.CrossRefPubMedADSGoogle Scholar
  14. 14.
    Chen JF, Luo Y, Xu JH, Chen QM, Guo J. Visualization study on sedimentation of micron iron oxide particles. J Colloid Interface Sci. 2006;301(2):549–53.CrossRefPubMedGoogle Scholar
  15. 15.
    Vesaratchanon JS, Nikolov A, Wasan DT. Sedimentation of concentrated monodisperse colloidal suspensions: role of collective particle interaction forces. J Colloid Interface Sci. 2008;322(1):180–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Leonhardt J, Arnold G, Baer M, Langguth H, Gey M, Hubert S. Radiation degradation of cellulose. Radiat Phys chem. 1985;25(4–6):899–904.Google Scholar
  17. 17.
    Park PJ, Je JY, Kim SK. Free radical scavenging activity of chitooligosaccharides by electron spin resonance spectrometry. J Agric Food Chem. 2003;51(16):4624–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Pekel N, Yoshii F, Kume T, Güven O. Radiation crosslinking of biodegradable hydroxypropylmethylcellulose. Carbohydr Polym. 2004;55(2):139–47.CrossRefGoogle Scholar
  19. 19.
    Bourges X, Schmitt M, Amouriq Y, Daculsi G, Legeay G, Weiss P. Interaction between hydroxypropyl methylcellulose and biphasic calcium phosphate after steam sterilisation: capillary gas chromatography studies. J Biomater Sci Polym Ed. 2001;12(6):573–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Fatimi A, Tassin JF, Axelos MAV, Weiss P. Sedimentation study of biphasic calcium phosphate particles. Key Eng Mater. 2008;361–363(1):365–8.CrossRefGoogle Scholar
  21. 21.
    Bouler JM, LeGeros RZ, Daculsi G. Biphasic calcium phosphates: influence of three synthesis parameters on the HA/beta-TCP ratio. J Biomed Mater Res. 2000;51(4):680–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Cross MM. Rheology of non-Newtonian fluids: a new flow equation for pseudoplastic systems. J Colloid Sci. 1965;20:417–26.CrossRefGoogle Scholar
  23. 23.
    van Doornmalen J, Kopinga K. Review of surface steam sterilization for validation purposes. Am J Infect Control. 2008;36(2):86–92.CrossRefPubMedGoogle Scholar
  24. 24.
    Roy J, Martyn MT, Tanner KE, Coates PD. Interfacial stick–slip transition in hydroxyapatite filled high density polyethylene composite. Bull Mater Sci. 2006;29(1):85–9.CrossRefGoogle Scholar
  25. 25.
    Li X, Ito A, Sogo Y, Wang X, Legeros RZ. Solubility of Mg-containing beta-tricalcium phosphate at 25°C. Acta Biomater. 2009;5(1):508–17.CrossRefPubMedGoogle Scholar
  26. 26.
    Fatimi A, Axelos MAV, Tassin JF, Weiss P. Rheological characterization of self-hardening hydrogel for tissue engineering applications: gel point determination and viscoelastic properties. Macromol Symp. 2008;266(1):12–6.CrossRefGoogle Scholar
  27. 27.
    Clasen C, Kulicke WM. Determination of viscoelastic and rheo-optical material functions of water-soluble cellulose derivatives. Prog Polym Sci. 2001;26(9):1839–919.CrossRefGoogle Scholar
  28. 28.
    Kryuchkov YN. Modeling of sedimentation processes for calculating the particle size distributions of disperse systems. Theor Found Chem Eng. 2005;39(5):522–8.CrossRefGoogle Scholar
  29. 29.
    Sarkar N. Thermal gelation properties of methyl and hydroxypropylmethylcellulose. J Appl Polym Sci. 1979;24:1073–87.CrossRefGoogle Scholar
  30. 30.
    Sarkar N. Kinetics of thermal gelation of methylcellulose and hydroxypropylmethylcellulose in aqueous solutions. Carbohydr Polym. 1995;26:195–203.CrossRefGoogle Scholar
  31. 31.
    Sarkar N, Walker LC. Hydration-dehydration properties of methylcellulose and hydroxypropylmethylcellulose. Carbohydr Polym. 1995;27:177–85.CrossRefGoogle Scholar
  32. 32.
    Bohic S, Weiss P, Roger P, Daculsi G. Light scattering experiments on aqueous solutions of selected cellulose ethers: contribution to the study of polymer–mineral interactions in a new injectable biomaterial. J Mater Sci Mater Med. 2001;12(3):201–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Fatimi A, Tassin JF, Turczyn R, Axelos MA, Weiss P. Gelation studies of a cellulose-based biohydrogel: the influence of pH, temperature and sterilization. Acta Biomater. 2009;5(9):3423–32.CrossRefPubMedGoogle Scholar
  34. 34.
    Richardson JF, Zaki WN. Sedimentation and fluidisation. Part 1. Trans Inst Chem Eng. 1954;32:35–53.Google Scholar
  35. 35.
    Brady JF, Durlofsky LJ. The sedimentation rate of disordered suspensions. Phys Fluids. 1988;31(4):717–27.CrossRefADSGoogle Scholar
  36. 36.
    Buscall R, White LR. The consolidation of concentrated suspensions. Part 1. The theory of sedimentation. J Chem Soc Faraday Trans 1. 1987;83:873–91.CrossRefGoogle Scholar
  37. 37.
    Al-Naafa MA, Selim MS. Sedimentation of monodisperse and bidisperse hard-sphere colloidal suspensions. AICHE J. 1992;38(10):1618–30.CrossRefGoogle Scholar
  38. 38.
    Auzerais FM, Jackson R, Russel WB. The resolution of shocks and the effects of compressible sediments in transient settling. J Fluid Mech. 1988;195:437–62.CrossRefADSGoogle Scholar
  39. 39.
    Allain C, Cloitre M, Parisse F. Settling by cluster deposition in aggregating colloidal suspensions. J Colloid Interface Sci. 1996;178(2):411–6.CrossRefGoogle Scholar
  40. 40.
    Daculsi G, Passuti N. Effect of the macroporosity for osseous substitution of calcium phosphate ceramics. Biomaterials. 1990;11:86–7.PubMedGoogle Scholar
  41. 41.
    Weiss P, Obadia L, Magne D, Bourges X, Rau C, Weitkamp T, et al. Synchrotron X-ray microtomography (on a micron scale) provides three-dimensional imaging representation of bone ingrowth in calcium phosphate biomaterials. Biomaterials. 2003;24(25):4591–601.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ahmed Fatimi
    • 1
    • 2
  • Jean-François Tassin
    • 3
  • Monique A. V. Axelos
    • 4
  • Pierre Weiss
    • 1
    • 2
  1. 1.Laboratoire d’Ingénierie Ostéo-Articulaire et Dentaire (LIOAD), INSERM U791Nantes Cedex 1France
  2. 2.Laboratoire d’Ingénierie Ostéo-Articulaire et Dentaire (LIOAD), Université de NantesNantes Cedex 1France
  3. 3.Laboratoire Polymères, Colloïdes, Interfaces (LPCI), UMR 6120CNRS, Université du MaineLe Mans Cedex 9France
  4. 4.INRA, UR1268 Biopolymères Interactions Assemblages (BIA)Nantes Cedex 3France

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