Research Article Characterization of an Ovine Bilateral Critical Sized Bone Defect Iliac Wing Model to Examine Treatment Modalities Based on Bone Tissue Engineering Jennifer L. Lansdowne, 1 Declan Devine, 1 Ursula Eberli, 1 Pieter Emans, 2 Tim J. M. Welting, 2 Jim C. E. Odekerken, 2 Damiano Schiuma, 1 Martin Thalhauser, 1 Ludovic Bouré, 1 and Stephan Zeiter 1 1 AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland 2 Department of Orthopaedic Surgery, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, 6202 AZ Maastricht, he Netherlands Correspondence should be addressed to Stephan Zeiter; stephan.zeiter@aofoundation.org Received 5 November 2013; Accepted 30 December 2013; Published 16 February 2014 Academic Editor: Aaron W. James Copyright © 2014 Jennifer L. Lansdowne et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Critical sized bone defect (CSBD) animal models are used to evaluate and conirm eicacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect let empty (negative control) or illed with autologous corticocancellous bone grat (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and luorochrome analysis. Ater three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. here were no intraoperative or postoperative complications. he model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering. 1. Introduction Before new treatment modalities based on bone tissue engi- neering can be used in clinical practice, their eicacy and potency require conirmation and evaluation in preclinical in vivo experiments, which oten requires the use of a critical sized bone defect (CSBD) animal model [1–3]. A CSBD is deined as the smallest bone defect in a particular bone and species of animal, which will not heal spontaneously during the lifetime of that animal [1, 4]. More speciically, a CSBD has been described as a defect that has less than 10 percent bony regeneration during the lifetime of the animal [2] or duration of the experiment [5]. CSBDs should result in the formation of ibrous connective tissue rather than bone when let untreated (negative control), so that the osteogenic poten- tial of the material being tested can be considered unequivo- cal [2]. Furthermore, CSBDs should heal when treated appro- priately, that is, with the current gold standard (autologous bone grat, positive control). Any new treatment based on bone tissue engineering has to be evaluated against these two landmarks. Additionally, the ideal CSBD animal model cre- ates little to no animal morbidity, has a low risk of com- plications, can provide more than one defect per animal in order to reduce the number of animals, can be imaged easily with advanced imaging techniques, and is reproducible. Last but not least, the defects should be of relevant size for neo- vascularization to occur, since vascularization remains one of the primary obstacles in the repair of bone defects [6, 7]. Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 250958, 7 pages http://dx.doi.org/10.1155/2014/250958