Animal models for implant biomaterial research in bone: A review

Abstract

Development of an optimal interface between bone and orthopaedic or dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species shows the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrates a good likeness with human bone, however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/ goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling will assist in the selection of a suitable model for a defined research question.

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

“…The bone maturation period in sheep is long and the microstructure in the young animals is distinct (plexiform bone). In adult sheep, the bone structure is different from humans, consists primarily of primary bone and Haversian remodelling occurs during adulthood [110]. The bone mineral density and bone strength in sheep is increased relative to human.…”

“…These models are more sophisticated because they require multiple procedures such as sciadic neurectomy, amputation or various immobilization techniques combined with bone defects [107,108]. The choice of the model should be based on scientific, ethical and practical merits of a particular study and reflect the human biology or disease and should accommodate for appropriate clinical settings with relevance to the product being tested [101,[109][110][111]. [16,112].…”

“…Additional factors that could influence selection of the animal model include the size of the animal, the cost to acquire and care for animals, animal availability, ethical acceptability, tolerance to captivity, breeding cycles, ease of housing and handling, adequate facilities and qualified staff and familiarity with the model, technical capacities etc. [109,110,125]. …”

“…Canine bone healing models are frequently used in musculoskeletal and dental research because significant amounts of information are available regarding the predictability of these models for human conditions [110,140,150]. Dog bones have a mixed microstructure with a primarily secondary osteonal bone and a plexiform bone in the vicinity of the periosteum and endosteum [140].…”

Spinal shape modulation in a porcine model by a highly flexible and extendable non-fusion implant system

“…It is believed to be the result of periosteal damage caused by implants rubbing against the spinous processes, lamina or facet joints during daily movements. Since facet and interlaminar fusions in lower animals, such as sheep, dogs, goats and pigs, are commonly achieved more easily than in humans [27,30], we consider this minor bone formation to be acceptable.…”