A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction.

Sparks, David S; Saifzadeh, Siamak; Savi, Flavia Medeiros; Dlaska, Constantin E; Berner, Arne; Henkel, Jan; Reichert, Johannes C; Wullschleger, Martin; Ren, Jiongyu; Cipitria, Amaia; McGovern, Jacqui A; Steck, Roland; Wagels, Michael; Woodruff, Maria Ann; Schuetz, Michael A; Hutmacher, Dietmar W

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.