The benefits and limitations of animal models for translational research in cartilage repair

Abstract

Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies. This review examines the in vivo models in current use for cartilage defect repair testing and the relevance of each in the context of generated results and applicability to bringing the device to clinical practice. Some of the preclinical models currently used include murine, leporine, ovine, caprine, porcine, canine, and equine models. Each of these has advantages and disadvantages in terms of animal husbandry, cartilage thickness, joint biomechanics and ethical and licencing issues. This review will examine the strengths and weaknesses of the various animal models currently in use in preclinical studies of cartilage repair.

Keywords: Cartilage; Collagen; In vivo; Osteochondral; Tissue engineering.

Fig. 1

Macroscopic image of distal femur of (a) rabbit, (b) goat and (c) horse showing (a) 3 mm, (b) 6 mm and (c) 9 mm defects created by drilling. This demonstrates the significant difference in the size of the joints involved and the size of the defects that can be created using these models. (Scale bar = 5 mm)

Fig. 2

H&E stained histology specimens of the distal femur of (a) rabbit (b) goat and (c) horse. These images demonstrate the histological similarity between the different models, but also the vast differences in the thickness of the cartilage at the joint surface. The chondrocyte distribution differences are also evident, with the rabbit cartilage being much more densely packed with chondrocytes than either goat or horse which could explain some better intrinsic healing of cartilage defects in rabbits

Fig. 3

2D micro-CT sections from rabbit (a) and goat (b) medial femoral condyles. These images demonstrate the similarity between the both models, with similar bone plate thickness and trabecular thickness in both cases. (Scale = 2 mm)

Fig. 4

Image of ultrasound of horse stifle taken one month post implantation of biomaterial scaffold (arrow) into naturally occurring osteochondral defect of trochlea of femur. This demonstrates the large defects occurring in the horse. The ability to image the implanted scaffold during the post-operative period is also a significant advantage to the large animal model