Heparinization of a biomimetic bone matrix: integration of heparin during matrix synthesis versus adsorptive post surface modification

  • Ulla König
  • Anja LodeEmail author
  • Petra B. Welzel
  • Yuichiro Ueda
  • Sven Knaack
  • Anja Henß
  • Anke Hauswald
  • Michael Gelinsky


This study intended to evaluate a contemporary concept of scaffolding in bone tissue engineering in order to mimic functions of the extracellular matrix. The investigated approach considered the effect of the glycosaminoglycan heparin on structural and biological properties of a synthetic biomimetic bone graft material consisting of mineralized collagen. Two strategies for heparin functionalization were explored in order to receive a three-component bone substitute material. Heparin was either incorporated during matrix synthesis by mixing with collagen prior to simultaneous fibril reassembly and mineralization (in situ) or added to the matrix after fabrication (a posteriori). Both methods resulted in an incorporation of comparable amounts of heparin, though its distribution in the matrix varied as indicated by TOF-SIMS analyses, and a similar modulation of their protein binding properties. Differential scanning calorimetry revealed that the thermal stability and thereby the degree of crosslinking of the heparinized matrices was increased. However, in contrast to the a posteriori modification, the in situ integration of heparin led to considerable changes of morphology and composition of the matrix: a more open network of collagen fibers yielding a more porous surface and a reduced mineral content were observed. Cell culture experiments with human mesenchymal stem cells (hMSC) revealed a strong influence of the mode of heparin functionalization on cellular processes, as demonstrated for proliferation and osteogenic differentiation of hMSC. Our results indicate that not only heparin per se but also the way of its incorporation into a collagenous matrix determines the cell response. In conclusion, the a posteriori modification was beneficial to support adhesion, proliferation and differentiation of hMSC.


Heparin Osteogenic Differentiation Matrix Synthesis Heparin Binding Bone Substitute Material 
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.



The authors thank the German Research Society (DFG) for financial support. This study was performed as part of the Collaborative Research Centre/Transregio 79 (SFB/TR 79, subproject M4). We thank Prof. Dr. M. Bornhäuser and co-workers (Medical Clinic I, University Hospital Carl Gustav Carus Dresden) for providing the hMSC. We are grateful to Ms. O. Zieschang for excellent technical assistance, Dr. B. Vetter (Institute for Material Science, Technische Universität Dresden) for the accomplishment of the mechanical tests as well as Dr. A. Bernhardt and Ms. B. Hoyer for fruitful discussions.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ulla König
    • 1
    • 3
  • Anja Lode
    • 1
    • 2
    Email author
  • Petra B. Welzel
    • 3
  • Yuichiro Ueda
    • 1
  • Sven Knaack
    • 1
    • 2
  • Anja Henß
    • 4
  • Anke Hauswald
    • 1
  • Michael Gelinsky
    • 1
    • 2
  1. 1.Max Bergmann Center of Biomaterials Dresden, Institute for Materials ScienceTechnische Universität DresdenDresdenGermany
  2. 2.Centre for Translational Bone, Joint and Soft Tissue ResearchUniversity Hospital Carl Gustav Carus and Medical Faculty of Technische Universität DresdenDresdenGermany
  3. 3.Leibniz Institute of Polymer Research Dresden e. V.DresdenGermany
  4. 4.Institute of Physical ChemistryJustus Liebig University GießenGiessenGermany

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