Effect of recombinant human bone morphogenic protein 9 (rhBMP9) loaded onto bone grafts versus barrier membranes on new bone formation in a rabbit calvarial defect model

J Biomed Mater Res A. 2017 Oct;105(10):2655-2661. doi: 10.1002/jbm.a.36125. Epub 2017 Jun 15.


Recent research has demonstrated that recombinant human bone morphogenetic protein 9 (rhBMP9) has been considered the most osteoinductive growth factor of the BMP-family. In the present study, rhBMP9 was investigated for its influence in combination with two biomaterials for bone regenerative medicine. Either porcine-derived collagen membrane (CM) or deproteinized bovine bone mineral (DBM) combined with 20 µg of rhBMP9 were implanted in 6 mm rabbit calvarial defects. Bone augmentation was evaluated by microCT and histomorphometry at 8 weeks post-surgery. Both CM + rhBMP9 and DBM + rhBMP9 groups significantly promoted mineralized tissue volume (microCT) and area, new bone height and area (histomorphometric measurements) when compared to CM and DBM alone groups or control (empty). All specimens in the CM + rhBMP9 group but not all in the DBM + rhBMP9 group induced a complete horizontal bone defect closure. Multinucleated giant cells (MNGCs) were observed directly in contact with DBM surfaces irrespective of rhBMP9, whereas CM was generally not associated to the presence of MNGCs. When combined with rhBMP9, DBM augmented a larger volume of mineralized tissue (including the mineralized bone graft), whereas CM induced greater volume of native host bone. While DBM in combination with rhBMP9 induced higher mineralized tissue mostly associated with the bone grafting material, CM may have presented preferable results based on a higher horizontal defect closure with a faster regeneration of host new bone. The effect of including collagen within the carrier system of rhBMP9 on bone regeneration justifies further evaluation of this combination procedure in larger animal models. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2655-2661, 2017.

Keywords: BMP-9; barrier membrane; bone morphogenetic proteins; guided bone regeneration.

MeSH terms

  • Animals
  • Bone Density
  • Bone Matrix / chemistry
  • Bone Regeneration / drug effects
  • Bone Substitutes / chemistry
  • Bone Substitutes / therapeutic use*
  • Collagen / chemistry
  • Collagen / therapeutic use
  • Drug Delivery Systems / methods
  • Female
  • Growth Differentiation Factor 2 / administration & dosage
  • Growth Differentiation Factor 2 / therapeutic use*
  • Guided Tissue Regeneration / methods*
  • Humans
  • Osteogenesis / drug effects*
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Skull / injuries*
  • Skull / pathology
  • Skull / physiology
  • Swine


  • Bone Substitutes
  • Growth Differentiation Factor 2
  • Recombinant Proteins
  • Collagen