Large Animal Models for Osteochondral Regeneration

Abstract

Namely, in the last two decades, large animal models - small ruminants (sheep and goats), pigs, dogs and horses - have been used to study the physiopathology and to develop new therapeutic procedures to treat human clinical osteoarthritis. For that purpose, cartilage and/or osteochondral defects are generally performed in the stifle joint of selected large animal models at the condylar and trochlear femoral areas where spontaneous regeneration should be excluded. Experimental animal care and protection legislation and guideline documents of the US Food and Drug Administration, the American Society for Testing and Materials and the International Cartilage Repair Society should be followed, and also the specificities of the animal species used for these studies must be taken into account, such as the cartilage thickness of the selected defect localization, the defined cartilage critical size defect and the joint anatomy in view of the post-operative techniques to be performed to evaluate the chondral/osteochondral repair. In particular, in the articular cartilage regeneration and repair studies with animal models, the subchondral bone plate should always be taken into consideration. Pilot studies for chondral and osteochondral bone tissue engineering could apply short observational periods for evaluation of the cartilage regeneration up to 12 weeks post-operatively, but generally a 6- to 12-month follow-up period is used for these types of studies.

Current Trends in the Evaluation of Osteochondral Lesion Treatments: Histology, Histomorphometry, and Biomechanics in Preclinical Models

“…In the literature, for each animal model, lesions of very different dimensions are found, involving or not the subchondral bone. Such a variety of in vivo protocols makes it difficult to establish a standard model as well as to compare results from different studies, also because the posttreatment evaluations can vary a lot among studies [8]. The complexity of the OC district gives the possibility of using a large number of assessments, ranging from histological stains specific for bone and cartilage to specific markers for cartilage regeneration/degeneration, new bone formation, mineralization status etc.…”

Animal Models of Osteochondral Defect for Testing Biomaterials

“…Before selecting an ideal animal model, it is crucial to decide whether a small or large animal model would be suitable for a particular OCD regeneration. e small animal models for OCD regeneration include rats and rabbits [13], while large animal models for OCD repair include dogs, pigs, sheep, goats, and horses [14]. Every animal has its advantages and limitations.…”

“…e dog is considered to be a very friendly and loving partner over the world. e social and ethical issues associated with the use of dogs as preclinical and translational animal models are main reasons for their limited use [14]. Dogs are susceptible to cartilage diseases such as exfoliative osteochondritis and osteoarthritis, and dogs lack the ability to repair cartilage defects intrinsically [31].…”

“…However, purchase and maintenance of pigs are very expensive. Pigs generally reach skeletal maturity in around 18 months [14]. Fisher et al [65] reported a cartilage thickness of 1.5 mm at the medial femoral condyle level in mini-pig.…”

<p>Ectopic chondrogenesis of nude mouse induced by nano gene delivery enhanced tissue engineering technology</p>

“…Most believe that the damage of mature articular cartilage is partial or superficial, and cartilage cannot regenerate itself 7–12. When the lesion is associated with the opening of the subchondral bone, cartilage repair can be completed because of the cells derived from bone marrow and blood vessels of subchondral bone 13–15. Even so, the repair cartilage has not been found to be the same as normal cartilage structure and mechanical properties, except embryonic stem cells 16,17.…”