Selection and Development of Preclinical Models in Fracture-Healing Research

Abstract

Animal fracture models have been extensively applied to preclinical research as a platform to identify and characterize normal and abnormal physiological processes and to develop specific maneuvers that alter the biology and biomechanics being examined. The choice of animal model employed in a study bears a direct relationship to the specific intervention being analyzed. The animal models employed should be described clearly, control-group data should be established, and reproducibility should be defined from experiment to experiment and from institution to institution so that quantitative and qualitative outcomes can be reliably compared and contrasted to other related studies.

Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

“…Large animal models provide mass and volume challenges for scaffold-based tissue engineering and require surgical fixation techniques that cannot be tested either in vitro or in small animal models (184). In general, preclinical translation testing is performed in large skeletally mature animals, the species most utilised are dog, sheep, goat and pig (192,199). If sufficient preclinical evidence for the efficacy and safety of the new bone tissue engineering system has been generated utilising large animal models, clinical trials care undertaken to prove clinical significance and safety, ultimately leading to the translation of the technology into routine clinical practice.…”

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…For example, aged, thyroparathyroidectomized and ovariectomized (OVX) animals are known for delayed fracture healing and reduced bone mineral density; therefore, OVX animals are frequently utilized to study osteoporotic fractures because these models mimic postmenopausal women [88,120,121]. Historic evidence suggests that rats, rabbits and mice are the most frequently used species to study bone physiology and drug efficacy and safety accounting for approximately 80% of all animals used to study bone repair, while other species including sheep, goats, pigs, dogs and non-human primates (NHP) make up for the remaining 20% [122,123]. The choice of a particular species is a critical step and is often based on the biochemical and microstructural characteristics of the bone tissue as well as on the similarities of the healing processes between the particular species and humans (Table 2, Figure 1).…”

Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

“…In vivo paracrine and autocrine signalling cascades leading to bone formation are complex and rely on strict spatiotemporal interplay between select growth factors. Teasing apart the individual roles that each growth factor plays within bone development and healing systems is of the highest (Aerssens et al, 1998;Kimmel and Jee, 1982;Neyt et al, 1998;Pearce et al, 2007;Skurla and James, 2005) (Aerssens et al, 1998;Mosekilde et al, 1993;Pearce et al, 2007;Thorwarth et al, 2005) Primates (Aerssens et al, 1998;Newman et al, 1995;Pearce et al, 2007;Ravaglioli et al, 1996) (Castaneda et al, 2006;Liebschner, 2004;Pearce et al, 2007) (Aerssens et al, 1998;Gomes and Fernandes, 2010;Liebschner, 2004;O'Loughlin et al, 2008) Table 4. Organic, inorganic and synthetic materials for orthopaedic applications in vivo.…”