Article
Establishing an extra-large segmental Tibial Defect Ovine Animal Model for bone regeneration
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Authors
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Jan Henkel
- Institute of Health and Biomedical Innovations, Queensland University of Technology, Kelvin Grove, Australia
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Constantin Dlaska
- Charité Universitätsmedizin Berlin, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
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Michael Schütz
- Charité Universitätsmedizin Berlin, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
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Dietmar Werner Hutmacher
- Institute of Health and Biomedical Innovations, Queensland University of Technology, Kelvin Grove, Australia
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Arne Berner
- Charité Universitätsmedizin Berlin, Centrum für Muskuloskeletale Chirurgie, Berlin, Germany
| Published: | October 23, 2017 |
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Outline
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Objectives: Well-characterised, reproducible and clinically relevant animal models are essential to generate proof-of-principle pre-clinical data necessary to advance novel therapeutic strategies into clinical trial and practical application. We have successfully established this 3 cm critical-sized defect model in sheep tibiae to study the mPCL-TCP scaffold in combination with cells or growth factors including bone morphogenic proteins (BMPs)
In the present study we established a 6cm tibial defect model to further investigate the bone regeneration potential of various TE approaches under well characterised and highly standardised conditions to mimic larger defects.
Methods: A 6cm segmental tibial bone defect was created in 8 adult merino sheep (aged 6-7 years). BMP-7 (2 mg) was mixed with autologous platelet rich plasma, transferred to the outer cortex of a tubular mPCL/TCP scaffold, and activated with thrombin (200 U/ml). The scaffolds were implanted into the created defects. Bone healing was assessed after 3 and 12 month post surgery by radiology, micro computed tomography, biomechanical testing and histology.
Results: All sheep tolerated the surgical procedure well, recovered fully from the procedure and returned to full weight bearing after cast removal. No implant failure occurred. The use of a 5.6mm 12 hole broad DCP chosen as implant were found to be sufficient to take the load associated with the increased defect size. Radiography showed increased bone formation over time with fully bridging of the defect after 12 month. MicroCT and Biomechanical testing confirmed the increased stability of the defect after 12 month.
Conclusion: The proposed aim to establish an extra-large tibial segmental bone defect ovine animal model has been successfully completed. Modifications to the surgical technique and implants used have been made effectively and standardized accordingly. Results indicate that the combination of mPCL-TCP scaffold with rhBMP-7, as investigated in the 3cm tibial defect model in the past, is effective for the regeneration of an increased defect size of 6cm. With the extra-large tibial bone defect model fully established at our research facility, we will be able to investigate novel bone grafting and bone tissue engineering applications under conditions that closely resemble the clinical situation.
