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

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Abstract

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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Authors and Affiliations

  1. Orthopedic Research Laboratory, Department of Orthopedics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Gerjon Hannink & Pieter Buma

  2. Department of Operating Rooms, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Gerjon Hannink

  3. Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

    Paul J. Geutjes

  4. Department of Biochemistry, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

    Paul J. Geutjes & Willeke F. Daamen

Authors
  1. Gerjon Hannink
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  2. Paul J. Geutjes
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  3. Willeke F. Daamen
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  4. Pieter Buma
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Correspondence to Gerjon Hannink.

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Gerjon Hannink, Paul J. Geutjes contributed equally to the study.

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Hannink, G., Geutjes, P.J., Daamen, W.F. et al. Evaluation of collagen/heparin coated TCP/HA granules for long-term delivery of BMP-2. J Mater Sci: Mater Med 24, 325–332 (2013). https://doi.org/10.1007/s10856-012-4802-4

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  • DOI: https://doi.org/10.1007/s10856-012-4802-4

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