Characterization of an Ovine Bilateral Critical Sized Bone Defect Iliac Wing Model to Examine Treatment Modalities Based on Bone Tissue Engineering

Jennifer L Lansdowne,Stephan Zeiter,Damiano Schiuma,Ludovic Bouré,Pieter Emans,Tim J M Welting,Declan Devine,Jim C E Odekerken,Ursula Eberli,Martin Thalhauser

doi:10.1155/2014/250958

Jennifer L Lansdowne, Stephan Zeiter + Show 8 more

Open Access

https://doi.org/10.1155/2014/250958

Copy DOI

Abstract

Critical sized bone defect (CSBD) animal models are used to evaluate and confirm efficacy 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 left empty (negative control) or filled with autologous corticocancellous bone graft (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After 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. There were no intraoperative or postoperative complications. The 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.

Highlights

The model described here represents a reliable and reproducible bilateral Critical sized bone defect (CSBD) in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering
Before new treatment modalities based on bone tissue engineering can be used in clinical practice, their efficacy and potency require confirmation and evaluation in preclinical in vivo experiments, which often requires the use of a critical sized bone defect (CSBD) animal model [1,2,3]
The ideal CSBD animal model creates little to no animal morbidity, has a low risk of complications, can provide more than one defect per animal in order to reduce the number of animals, can be imaged with advanced imaging techniques, and is reproducible

Summary

Introduction

Before new treatment modalities based on bone tissue engineering can be used in clinical practice, their efficacy and potency require confirmation and evaluation in preclinical in vivo experiments, which often requires the use of a critical sized bone defect (CSBD) animal model [1,2,3]. A CSBD is defined 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]. 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]. Any new treatment based on bone tissue engineering has to be evaluated against these two landmarks. The defects should be of relevant size for neovascularization to occur, since vascularization remains one of the primary obstacles in the repair of bone defects [6, 7]

Objectives

Methods

Conclusion