Critical-size bone defects, which require large-volume tissue reconstruction, remain a clinical challenge. Bone engineering has the potential to provide new treatment concepts, yet clinical translation requires anatomically and physiologically relevant preclinical models. The ovine critical-size long-bone defect model has been validated in numerous studies as a preclinical tool for evaluating both conventional and novel bone-engineering concepts. With sufficient training and experience in large-animal studies, it is a technically feasible procedure with a high level of reproducibility when appropriate preoperative and postoperative management protocols are followed. The model can be established by following a procedure that includes the following stages: (i) preoperative planning and preparation, (ii) the surgical approach, (iii) postoperative management, and (iv) postmortem analysis. Using this model, full results for peer-reviewed publication can be attained within 2 years. In this protocol, we comprehensively describe how to establish proficiency using the preclinical model for the evaluation of a range of bone defect reconstruction options.
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The datasets that support this study are available from the corresponding author upon request.
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This work was supported by the German Research Foundation (DFG; BE 4492/1-2 and HE 7074/1-1) and the Australian Research Council (ARC LP100200084, ARC IC160100026, Industrial Transformation Training Centre in Additive Biomanufacturing, ARC Future Fellowship awarded to D.W.H.). This work was also supported by funding through the Wesley Hospital Foundation, the AO Foundation and the Princess Alexandra Hospital Research Foundation. We thank the staff at the Queensland University of Technology (QUT) Medical Engineering Research Facility for veterinary assistance and administrative and technical support.
D.W.H. is a cofounder and shareholder of Osteopore International Pty Ltd, a company specializing in 3D bioresorbable implants to assist with bone healing.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Sparks, D.S., Saifzadeh, S., Savi, F.M. et al. A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction. Nat Protoc 15, 877–924 (2020). https://doi.org/10.1038/s41596-019-0271-2
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