Small-sized granules of biphasic bone substitutes support fast implant bed vascularization

Biomatter. 2015;5(1):e1056943. doi: 10.1080/21592535.2015.1056943.


The present study investigated the influence of granule size of 2 biphasic bone substitutes (BoneCeramic® 400-700 μm and 500-1000 μm) on the induction of multinucleated giant cells (MNGCs) and implant bed vascularization in a subcutaneous implantation model in rats. Furthermore, degradation mechanisms and particle phagocytosis of both materials were examined by transmission electron microscopy (TEM). Both granule types induced tissue reactions involving primarily mononuclear cells and only small numbers of MNGCs. Higher numbers of MNGCs were detected in the group with small granules starting on day 30, while higher vascularization was observed only at day 10 in this group. TEM analysis revealed that both mono- and multinucleated cells were involved in the phagocytosis of the materials. Additionally, the results allowed recognition of the MNGCs as the foreign body giant cell phenotype. Histomorphometrical analysis of the size of phagocytosed particles showed no differences between the 2 granule types. The results indicate that granule size seems to have impact on early implant bed vascularization and also on the induction of MNGCs in the late phase of the tissue reaction. Furthermore, the results revealed that a synthetic bone substitute material can induce tissue reactions similar to those of some xenogeneic materials, thus pointing to a need to elucidate their "ideal" physical characteristics. The results also show that granule size in the range studied did not alter phagocytosis by mononuclear cells. Finally, the investigation substantiates the differentiation of material-induced MNGCs, which are of the foreign body giant cell type.

Keywords: BoneCeramic; biphasic bone substitute; degradation; granule size; multinucleated giant cells; phagocytosis; vascularization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Substitutes / pharmacology*
  • Bone and Bones / blood supply*
  • Bone and Bones / immunology*
  • Disease Models, Animal
  • Female
  • Giant Cells / metabolism*
  • Hydroxyapatites / pharmacology*
  • Leukocytes, Mononuclear / metabolism*
  • Materials Testing
  • Mice
  • Microscopy, Electron, Scanning
  • Neovascularization, Physiologic
  • Particle Size
  • Phagocytosis
  • Rats


  • Bone Substitutes
  • BoneCeramic
  • Hydroxyapatites