title: Bone morphogenetic protein-2 and growth and differentiation factor-5 enhance the healing of necrotic bone in a sheep model.
abstract: BACKGROUND
  Osteotropic growth factors enhance bone repair, but their efficacy in an area of necrotic bone is not known. The purpose of this study was to investigate the effects and potential side effects of an intraosseous application of absorbable bone morphogenetic protein-2 (BMP-2) and growth and differentiation factor-5 (GDF-5) composites in a sheep model for partial necrosis of the femoral head.
  
  
  METHODS
  The direct injection of ethanol under fluoroscopy into the superior centre of the right femoral head produced histologically documentable necrosis of the central region of the head in a previous study of ten sheep. Another 27 sheep constituted the sample to study the effects of BMP-2 and GDF-5. Necrosis was produced in the same fashion in these animals. Four weeks later nine sheep received 300 microg recombinant BMP-2 and nine sheep 300 microg recombinant GDF-5 on an absorbable carrier by surgical implantation. Nine sheep received the carrier alone (control group). The animals were sacrificed at 3, 6, and 12 weeks after implantation and both femora were harvested.
  
  
  RESULTS
  Bone density analysis and microscopic examination indicated that bone formation was noticeably induced as early as 3 weeks postoperatively in the growth factor treated animals. Bone regeneration was enhanced by growth factor composites. This was documented by histological scoring and histomorphometric analysis. No severe local side effects secondary to the growth factors, such as heterotopic ossification or inflammation, were observed in either group.
  
  
  CONCLUSIONS
  The application of an absorbable growth factor composite in combination with established surgical techniques is a promising approach, that may enhance the healing of devitalised bone defects. Based on these results, further studies regarding biodegradation, dosage of the protein and surgical technique are required.
authors.affiliation: Department of Orthopaedics, University of Heidelberg, Germany. hans-georg.simank@ok.uni-heidelberg.de
authors.forename: H G
authors.initials: HG
authors.lastname: Simank
authors.forename: J
authors.initials: J
authors.lastname: Manggold
authors.forename: W
authors.initials: W
authors.lastname: Sebald
authors.forename: R
authors.initials: R
authors.lastname: Ries
authors.forename: W
authors.initials: W
authors.lastname: Richter
authors.forename: V
authors.initials: V
authors.lastname: Ewerbeck
authors.forename: C
authors.initials: C
authors.lastname: Sergi
mesh_terms: D000818:Animals; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D001842:Bone and Bones / Q000473:pathology*; D004926:Escherichia coli / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D009336:Necrosis; D011994:Recombinant Proteins; D012756:Sheep; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D016212:Transforming Growth Factor beta; D014945:Wound Healing
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000431:Ethanol