Guided bone regeneration with recombinant human bone morphogenetic protein 9 loaded on either deproteinized bovine bone mineral or a collagen barrier membrane

Clin Implant Dent Relat Res. 2017 Aug;19(4):600-607. doi: 10.1111/cid.12491. Epub 2017 May 2.


Background: Recombinant human bone morphogenetic protein 9 (rhBMP9) has been considered the most osteoinductive growth factor of the BMP-family and has much translation potential for guided bone regeneration (GBR) procedures.

Purpose: The aim of this study was to compare bone formation using rhBMP9 loaded with different carrier systems including deprotenized bovine bone mineral (BioOss, BO) or collagen barrier membranes (BioGide, BG) in a rabbit GBR model.

Materials and methods: rhBMP9 was loaded either on BO; named BO/BMP9, or BG; named BG/BMP9 to investigate the better carrier system for rhBMP9. New bone formation was quantified in a rabbit calvarial defect model using four groups; (1) control (empty, n = 9), (2) BO + BG (n = 9), (3) BO/BMP9 + BG (n = 9; BMP9 loaded onto BO), and (4) BO + BG/BMP9 (n = 9; BMP9 loaded onto BG) by radiographically and histologically at 8 weeks post-surgery.

Results: Both BO/BMP9 + BG and BO + BG/BMP9 samples significantly promoted new bone formation when compared to BO + BG samples based on parameters including mineralized tissue volume by microCT analysis, as well as new bone height and new bone area by histomorphometry. Interestingly, BO + BG/BMP9 samples but not BO/BMP9 + BG achieved near perfect horizontal bone defect closure, while demonstrating new bone layers in the defect areas implanted with BG materials and bone formation around BO materials.

Conclusion: Both BO and BG positively induced bone formation with rhBMP9 in an experimental rabbit GBR model when compared to BO + BG alone. This study revealed that BG-loaded with rhBMP9 promoted better wound closure when compared to BO-loaded with rhBMP9. GBR procedures with growth factors may thus benefit from loading rhBMP9 onto BG-collagen barrier membranes when compared to BO-bone grafting particles. Future large animal studies with different types of bone grafts and barrier membranes are needed to further investigate these trends.

Keywords: BMP9; GBR; bone formation; bone induction; bone morphogenetic protein; guided bone regeneration; rhBMP9.

MeSH terms

  • Animals
  • Bone Development / drug effects*
  • Cattle
  • Collagen / metabolism
  • Female
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors / therapeutic use*
  • Guided Tissue Regeneration / methods*
  • Rabbits
  • Recombinant Proteins / therapeutic use
  • Skull / diagnostic imaging
  • Skull / drug effects
  • Skull / growth & development
  • Skull / surgery
  • X-Ray Microtomography


  • GDF2 protein, human
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors
  • Recombinant Proteins
  • Collagen