A comparison of the microarchitecture of lower limb long bones between some animal models and humans: a review

Animal models are unavoidable and indispensable research tools in the fields of bone tissue engineering and experimental orthopaedics. The fact that there is not ideal animal model as well as the differences in the bone microarchitecture and physiology between animals and humans are complicate factors and make model implementation difficult. Therefore, the tendency should be directed towards extrapolation of the results from one animal model to another or from animal model to humans. So far, this is the first paper which provides an overview on the microarchitecture of lower limb long bones and discusses data related to osteon diameter, osteon canal diameter and their orientation, as well as intracortical canals and trabecular tissue microarchitecture in commonly used animal models compared to humans depending on age, gender and anatomical location of the bone. Understanding the differences between animal model and human bone microarchitecture should enable a more accurate extrapolation of experimental results from one animal model to another or from animal models to humans in the fields of bone tissue engineering and experimental orthopaedics. Also, this should be helpful in making decisions on which animal models are the most suitable for particular preclinical testing.  

Download Full-text

THE IMPORTANCE OF LARGE ANIMAL MODELS FOR TRANSLATIONAL RESEARCH IN BONE TISSUE ENGINEERING

Reproduction Fertility and Development ◽

10.1071/rdv24n1ab249 ◽

2012 ◽

Vol 24 (1) ◽

pp. 287

Author(s):

S. J. Hollister ◽

M. B. Wheeler ◽

S. E. Feinberg ◽

W. L. Murphy

Keyword(s):

Tissue Engineering ◽

Animal Model ◽

Animal Models ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Large Animal ◽

Engineering Studies ◽

Large Animal Models ◽

Clinical Indications ◽

Human Situation

The translation of bone tissue engineering (BTE) research to clinical use has been absymal1. Outside of bone void filler biomaterials, only Bone Morphogenetic Protein 2 (BMP2) has made significant inroads to clinical practice, and even BMP2 use has been associated with significant complications including death, dysphagia, and ectopic bone formation. The dearth of BTE products can be attributed to two main causes: (1) the need to develop BTE systems, that successfully integrate scaffolds, growth factors like BMP2 and cells and (2) the need to adapt and implement such systems for a wide variety of clinical indications in CranioMaxilloFacial (CMF), Spine and Orthopedic Surgery. Of course, to fully develop BTE systems (Issue 1) and adapt them to realistic clinical indications, we must be able to test such systems in bone defects that are as close to the human situation as possible. Thus, the use of domestic large animals for bone tissue engineering is critical, as these animals provide challenges in both defect volume and functional loading that can mimic the human situation. In addition, FDA approval for BTE products either through a 510K or IDE/IND/PMA pathway requires the use of a large pre-clinical animal model. However, despite this need, only approximately 60 large animal bone tissue-engineering studies have been published in the past 10 years. Furthermore, NIH has funded only 8% of these studies, and of the 17 bone tissue engineering studies supported by NIH in 2010, only three utilized a large animal model, and none of these used an animal larger than a rabbit. Clearly, increased translation and regulatory approval of BTE therapies will require greater testing in large animal models. We will discuss the current dearth of relevant pre-clinical studies in BTE, and present our work addressing these issues by developing BTE systems (integrated scaffold, growth factor and stem-cell constructs) and testing these systems for realistic clinical applications using the Yorkshire and other swine species as a large pre-clinical animal model. We will detail our work in developing BTE systems for CMF reconstruction and spine fusion in the swine model. Reference Hollister S. J. and Murphy W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. B. (in press).

Download Full-text