In vivo release of rhBMP-2 loaded porous calcium phosphate cement pretreated with albumin

  • P. Q. Ruhé
  • O. C. Boerman
  • F. G. M. Russel
  • A. G. Mikos
  • P. H. M. Spauwen
  • J. A. Jansen
Article

Abstract

In this study, the release of rhBMP-2 loaded porous Ca-P cement was studied in vitro and in vivo. We hypothesized that adsorption sites of Ca-P ceramic with high affinity for rhBMP-2 can be blocked by pretreatment of the ceramic with albumin prior to rhBMP-2 loading, which would result in weaker rhBMP-2 binding and enhanced release of rhBMP-2. Preset porous Ca-P cement discs with a diameter of 6.35 mm (volume: 75 mm3) were pretreated by incubation in a solution of 10% rat serum albumin for 24 h or in ddH2O (control group) prior to administration of 5 μg radiolabeled 131I-rhBMP-2. Release was assessed in vitro in phosphate buffered saline (PBS) and fetal calf serum and in vivo by longitudinal scintigraphic imaging of radiolabeled 131I-rhBMP-2 and gamma counting of dissected implants.

In vitro release from pretreated discs was higher during the first day. For both formulations, release in PBS was limited compared to release in serum. In vivo release considerably exceeded in vitro release. In vivo release kinetics showed no significant difference of half-lives between pretreated and control discs. Both formulations showed sustained release during at least 4 weeks. Ex vivo gamma counting of retrieved samples confirmed scintigraphic results and showed that the capsule and surrounding tissues only contained a minor fraction rhBMP-2. We conclude that 1. scintigraphy of 131I-labeled rhBMP-2 provides a reliable method for longitudinal measurement of rhBMP-2 release kinetics in vivo. 2. albumin pretreatment of porous Ca-P cement does not results in relevant increase of initial release of rhBMP-2 in vivo, and 3. preset rhBMP-2 loaded porous Ca-P cement discs exhibit one phase exponential release kinetics in the rat ectopic model, characterized by a retention of 20–30% after 4 weeks.

References

  1. 1.
    M. MURATA, M. INOUE, M. ARISUE, Y. KUBOKI and N. NAGAI, Int J. Oral. Maxillofac Surg. 27 (1998) 391–396.CrossRefGoogle Scholar
  2. 2.
    H. ULUDAG, D. D’AUGUSTA, R. PALMER, G. TIMONY and J. WOZNEY, J. Biomed. Mater. Res. 46 (1999) 193–202.CrossRefGoogle Scholar
  3. 3.
    H. ULUDAG, D. D’AUGUSTA, J. GOLDEN, J. LI, G. TIMONY, R. RIEDEL and J. M. WOZNEY, J. Biomed. Mater. Res. 50 (2000) 227–238.CrossRefGoogle Scholar
  4. 4.
    Y. KUBOKI, Q. JIN and H. TAKITA, J. Bone. Joint. Surg. Am. 83-A (1) (2001) 105–115.Google Scholar
  5. 5.
    S. A. CLARKE, R. A. BROOKS, P. T. LEE and N. RUSHTON, J. Bone. Joint. Surg. Br. 86 (2004) 126–134.Google Scholar
  6. 6.
    J. A. KOEMPEL, B. S. PATT, K. O’GRADY, J. WOZNEY and D. M. TORIUMI, J. Biomed. Mater. Res. 41 (1998) 359–363.CrossRefGoogle Scholar
  7. 7.
    H. C. KROESE-DEUTMAN, P. Q. RUHE, P. H. SPAUWEN and J. A. JANSEN, Biomaterials 26 (2005) 1131–1138.CrossRefGoogle Scholar
  8. 8.
    J. LOUIS-UGBO, H. S. KIM, S. D. BODEN, M. T. MAYR, R. C. LI, H. SEEHERMAN, D. D’AUGUSTA, C. BLAKE, A. JIAO and S. PECKHAM, J. Orthop. Res. 20 (2002) 1050–1059.CrossRefGoogle Scholar
  9. 9.
    I. ONO, T. TATESHITA and Y. KUBOKI, J. Biomed. Mater. Res. 45 (1999) 337–344.CrossRefGoogle Scholar
  10. 10.
    P. Q. RUHE, H. C. KROESE-DEUTMAN, J. G. WOLKE, P. H. SPAUWEN and J. A JANSEN, Biomaterials 25 (2004) 2123–2132.CrossRefGoogle Scholar
  11. 11.
    H. TERHEYDEN, C. KNAK, S. JEPSEN, S. PALMIE and D. R. RUEGER, Int. J. Oral. Maxillofac. Surg. 30 (2001) 373–379.CrossRefGoogle Scholar
  12. 12.
    S. J. MERAW, C. M. REEVE, C. M. LOHSE and T. M. SIOUSSAT, J Periodontol 71 (2000) 8–13.CrossRefGoogle Scholar
  13. 13.
    D. R. SUMNER, T. M. TURNER, R. M. URBAN, T. TUREK, H. SEEHERMAN and J. M. WOZNEY, J. Orthop. Res. 22 (2004) 58–65.CrossRefGoogle Scholar
  14. 14.
    U. RIPAMONTI, J. CROOKS and D. C. RUEGER, Plast. Reconstr. Surg. 107 (2001) 977–988.CrossRefGoogle Scholar
  15. 15.
    S. D. BODEN, G. J. MARTIN J r., M. A. MORONE, J. L. UGBO and P. A. MOSKOVITZ, Spine 24 (1999) 1179–1185.CrossRefGoogle Scholar
  16. 16.
    R. H. LI, M. L. BOUXSEIN, C. A. BLAKE, D. D’AUGUSTA, H. KIM, X. J. LI, J. M. WOZNEY and H. J. SEEHERMAN, J. Orthop. Res. 21 (2003) 997–1004.CrossRefGoogle Scholar
  17. 17.
    A. H. REDDI and N. S. CUNNINGHAM, J. Bone. Miner. Res. 8(2) (1993) 499–502.Google Scholar
  18. 18.
    H. ULUDAG, T. GAO, T. J. PORTER, W. FRIESS and J. M. WOZNEY, J. Bone. Joint Surg. Am. 83-A(1) (2001) 128–35.Google Scholar
  19. 19.
    N. S. CUNNINGHAM, V. PARALKAR and A. H. REDDI, Proc. Natl. Acad. Sci. USA 89 (1992) 11740–4.CrossRefGoogle Scholar
  20. 20.
    M. S. TUNG and D. SKRTIC, In: ‘Monogr Oral Sci., Octacalcium Phospate[18],’ edited by L. C. CHOW and E. D EANES, (Karger AG. Basel, 2001) 112–129.Google Scholar
  21. 21.
    K. MISHRA, S. HANDLER and W. FUERSTENAU, Colloids Surfaces 1 (1980) 105–119.CrossRefGoogle Scholar
  22. 22.
    S. CHANDLER and D. W. FUERSTENAU, In: ‘Adsorption on and Surface Chemistry of Hydroxyapatite,’ edited by D. N. MISRA. (Plenum Press, New York. 1984) 29–49.Google Scholar
  23. 23.
    M. S. TUNG and W. E. BROWN, Caries Res. 19 (1985) 72–75.CrossRefGoogle Scholar
  24. 24.
    R. P. DEL REAL, J. G. WOLKE, M. VALLET-REGI and J. A. JANSEN, Biomaterials 23 (2002) 3673–80.CrossRefGoogle Scholar
  25. 25.
    P. J. FRAKER and J. C., JR. SPECK, Biochem. Biophys. Res. Commun. 80 (1978) 849–857.CrossRefGoogle Scholar
  26. 26.
    M. E. BAKER, J. Endocrinol. 175 (2002) 121–127.CrossRefGoogle Scholar
  27. 27.
    A. ROSENGREN, E. PAVLOVIC, S. OSCARSSON, A. KRAJEWSKI, A. RAVAGLIOLI and A. PIANCASTELLI, Biomaterials 23 (2002) 1237–1247.CrossRefGoogle Scholar
  28. 28.
    J. R. SHARPE, R. L. SAMMONS and P. M. MARQUIS, Biomaterials 18 (1997) 471–476.CrossRefGoogle Scholar
  29. 29.
    A. P. SERRO, M. BASTOS, J. C. PESSOA and B. SARAMAGO, J. Biomed. Mater. Res. 70A (2004) 420–427.CrossRefGoogle Scholar
  30. 30.
    B. FENG, J. CHEN and X. ZHANG, Biomaterials 23 (2002) 2499–2507.CrossRefGoogle Scholar
  31. 31.
    M. LIND, S. OVERGAARD, K. SOBALLE, T. NGUYEN, B. ONGPIPATTANAKUL and C. BUNGER, J. Orthop. Res. 14 (1996) 343–350.CrossRefGoogle Scholar
  32. 32.
    P. LAFFARGUE, P. FIALDES, P. FRAYSSINET, M. RTAIMATE, H. F. HILDEBRAND and X. MARCHANDISE, J. Biomed. Mater. Res. 49 (2000) 415–421.CrossRefGoogle Scholar
  33. 33.
    C. COMBES and C. REY, Biomaterials 23 (2002) 2817–2823.CrossRefGoogle Scholar
  34. 34.
    S. RADIN, P. DUCHEYNE, P. BERTHOLD and S. DECKER, J. Biomed. Mater. Res. 39 (1998) 234–243.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • P. Q. Ruhé
    • 1
  • O. C. Boerman
    • 2
  • F. G. M. Russel
    • 3
  • A. G. Mikos
    • 4
  • P. H. M. Spauwen
    • 5
  • J. A. Jansen
    • 1
  1. 1.Department of Perio-Dontology and BiomaterialsRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  2. 2.Department of Nuclear MedicineRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  3. 3.Department of Pharmacology and ToxicologyRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  4. 4.Department of BioengineeringRice UniversityHoustonUSA
  5. 5.Department of Plastic and Reconstructive SurgeryRadboud University Nijmegen Medical CenterNijmegenThe Netherlands

Personalised recommendations