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01.12.2016 | Research article | Ausgabe 1/2016 Open Access

BMC Musculoskeletal Disorders 1/2016

Establishment of a preclinical ovine screening model for the investigation of bone tissue engineering strategies in cancellous and cortical bone defects

BMC Musculoskeletal Disorders > Ausgabe 1/2016
Anne-Marie Pobloth, Kenneth A. Johnson, Hanna Schell, Nicolai Kolarczik, Dag Wulsten, Georg N. Duda, Katharina Schmidt-Bleek
Wichtige Hinweise

Competing interest

The authors declare that they have no competing interests.

Authors’ contributions

AP contributed to study planning and wrote the ethical approval. She performed the surgeries, anesthesia and animal care. She participated in the biomechanical testing and performance of radiographic images. She performed the data acquisition, data interpretation, statistical analysis, wrote the manuscript, and prepared the images. KJ contributed to study planning and acquisition of data. He performed the surgeries and revised the manuscript. HS contributed to study planning, drafting the manuscript, performance of surgeries, anesthesia, animal care, biomechanical testing, and acquisition of data. NK contributed to performance of animal surgeries, animal care, radiographic images, and acquisition of data. DW planned and performed the biomechanical testing, acquisition of data, and revised the manuscript. GD planned and supervised the study, raised the funds, interpreted the data, and revised the manuscript. KS planned the study, participated in the biomechanical testing, data acquisition, data interpretation, drafting the manuscript, and revision. She created the drawings and contributed to performance of surgeries, animal care, and anesthesia. All authors read and approved the final manuscript.



New tissue engineering strategies for bone regeneration need to be investigated in a relevant preclinical large animal model before making the translation into human patients. Therefore, our interdisciplinary group established a simplified large animal screening model for intramembranous bone defect regeneration in cancellous and cortical bone.


Related to a well-established model of cancellous drill hole defect regeneration in sheep, both the proximal and distal epimetaphyseal regions of the femur and the humerus were used bilaterally for eight drill hole cancellous defects (Ø 6 mm, 15 mm depth). Several improvements of the surgical procedure and equipment for an easier harvest of samples were invented. For the inclusion of cortical defect regeneration, a total of eight unicortical diaphyseal drill holes (6 mm Ø) were placed in the proximal-lateral and distal-medial parts of the metacarpal (MC) and metatarsal (MT) diaphyseal bone bilaterally. Acting moments within a normal gait cycle in the musculoskeletal lower limb model were compared with the results of the biomechanical in vitro torsion test until failure to ensure a low accidental fracture risk of utilized bones (ANOVA, p < 0.05). The model was tested in vivo, using thirteen adult, female, black-face sheep (Ø 66 kg; ± 5 kg; age ≥ 2.5 years). In a two-step surgical procedure 16 drill holes were performed for the investigation of two different time points within one animal. Defects were left empty, augmented with autologous cancellous bone or soft bone graft substitutes.


The in vitro tests confirmed this model a high comparability between drilled MC and MT bones and a high safety margin until fracture. The exclusion of one animal from the in vivo study, due to a spiral fracture of the left MC bone led to a tolerable failure rate of 8 %.


As a screening tool, promising biomaterials can be tested in this cancellous and cortical bone defect model prior to the application in a more complex treatment site.
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