Evaluation of collagen/heparin coated TCP/HA granules for long-term delivery of BMP-2

  • Gerjon Hannink
  • Paul J. Geutjes
  • Willeke F. Daamen
  • Pieter Buma


Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. The purpose of this study was to develop a sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2). We covalently attached heparin to a cross-linked collagen type I coated tricalciumphosphate/hydroxyapatite (TCP/HA) bone substitute and subsequently loaded it with BMP-2. To systematically evaluate the contribution of each component with respect to the binding and release of BMP-2, six constructs were prepared and characterized: TCP/HA, TCP/HA with collagen (TCP/HACol), and TCP/HA with collagen and heparin (TCP/HAColHep) with and without BMP-2 (B). More BMP-2 bound to the TCP/HAColHep + B (92.9 ± 4.8 ng BMP-2/mg granule) granules as compared to the TCP/HACol + B (69.0 ± 9.6 ng BMP-2/mg granule) and TCP/HA + B granules (62.9 ± 5.4 ng BMP-2/mg granule). No difference in release pattern was found between the TCP/HA + B and TCP/HACol + B granules. Up to day 14, BMP-2 was still bound to the TCP/HAColHep + B granules, whereas most BMP had been released from TCP/HACol + B and TCP/HA + B granules at that time. After 21 days most BMP-2 also had been released from the TCP/HAColHep + B granules. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and could possibly enhance bone regeneration efficacy for the treatment of large bone defects.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Gerjon Hannink
    • 1
    • 2
  • Paul J. Geutjes
    • 3
    • 4
  • Willeke F. Daamen
    • 4
  • Pieter Buma
    • 1
  1. 1.Orthopedic Research Laboratory, Department of OrthopedicsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of Operating RoomsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Department of UrologyRadboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life SciencesNijmegenThe Netherlands
  4. 4.Department of BiochemistryRadboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life SciencesNijmegenThe Netherlands

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