Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur

Werner Hettwer, Peter F Horstmann, Sabine Bischoff, Daniel Güllmar, Jürgen R Reichenbach, Patrina S P Poh, Martijn van Griensven, Florian Gras, Michael Diefenbeck


Assessment of bone graft material efficacy is difficult in humans, since invasive methods like staged CT scans or biopsies are ethically unjustifiable. Therefore, we developed a novel large animal model for the verification of a potential transformation of synthetic bone graft substitutes into vital bone. The model combines multiple imaging methods with corresponding histology in standardized critical sized cancellous bone defect. Cylindrical bone voids (10 ml) were created in the medial femoral condyles of both hind legs (first surgery at right hind leg, second surgery 3 months later at left hind leg) in three merino-wool sheep and either (i) left empty, filled with (ii) cancellous allograft bone or (iii) a synthetic, gentamicin eluting bone graft substitute. All samples were analysed with radiographs, MRI, μCT, DEXA and histology after sacrifice at 6 months. Unfilled defects only showed ingrowth of fibrous tissue, whereas good integration of the cancellous graft was seen in the allograft group. The bone graft substitute showed centripetal biodegradation and new trabecular bone formation in the periphery of the void as early as 3 months. μCT gave excellent insight into the structural changes within the defects, particularly progressive allograft incorporation and the bone graft substitute biodegradation process. MRI completed the picture by clearly visualizing soft tissue ingrowth into unfilled bone voids and presence of fluid collections. Histology was essential for verification of trabecular bone and osteoid formation. Conventional radiographs and DEXA could not differentiate details of the ongoing transformation process. This model appears well suited for detailed in vivo and ex vivo evaluation of bone graft substitute behaviour within large bone defects.

Original languageEnglish
JournalAPMIS - Journal of Pathology, Microbiology and Immunology
Issue number2
Pages (from-to)53-63
Number of pages11
Publication statusPublished - Feb 2019


  • Allografts
  • Animals
  • Bone Substitutes/therapeutic use
  • Bone Transplantation/methods
  • Calcium Sulfate
  • Cancellous Bone/growth & development
  • Durapatite
  • Female
  • Femur/surgery
  • Magnetic Resonance Imaging
  • Models, Animal
  • Sheep


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