Animal models for cartilage regeneration and repair

Abstract

Articular cartilage injury and degeneration are leading causes of disability. Animal studies are critically important to developing effective treatments for cartilage injuries. This review focuses on the use of animal models for the study of the repair and regeneration of focal cartilage defects. Animals commonly used in cartilage repair studies include murine, lapine, canine, caprine, porcine, and equine models. There are advantages and disadvantages to each model. Small animal rodent and lapine models are cost effective, easy to house, and useful for pilot and proof-of-concept studies. The availability of transgenic and knockout mice provide opportunities for mechanistic in vivo study. Athymic mice and rats are additionally useful for evaluating the cartilage repair potential of human cells and tissues. Their small joint size, thin cartilage, and greater potential for intrinsic healing than humans, however, limit the translational value of small animal models. Large animal models with thicker articular cartilage permit study of both partial thickness and full thickness chondral repair, as well as osteochondral repair. Joint size and cartilage thickness for canine, caprine, and mini-pig models remain significantly smaller than that of humans. The repair and regeneration of chondral and osteochondral defects of size and volume comparable to that of clinically significant human lesions can be reliably studied primarily in equine models. While larger animals may more closely approximate the human clinical situation, they carry greater logistical, financial, and ethical considerations. A multifactorial analysis of each animal model should be carried out when planning in vivo studies. Ultimately, the scientific goals of the study will be critical in determining the appropriate animal model.

FIG. 1.

Histology of mouse articular cartilage. Histological section of the murine distal femur shows the extreme thinness of the articular cartilage consisting of only a few cell layers above the tidemark (arrows). Color images available online at www.liebertonline.com/ten.

FIG. 2.

Rat osteochondral defect model. (A) 1.5 mm osteochondral defect drilled into the rat trochlear groove. (B) Defect filled with PEG-genipin scaffold. Color images available online at www.liebertonline.com/ten.

FIG. 3.

Histology of porcine articular cartilage. (A) Histological section of porcine articular cartilage shows cartilage thickness greater than 1 mm. (B) Histological section of porcine articular cartilage after radiofrequency treatment shows that this tissue is thick enough for the creation of a partial thickness defect. Color images available online at www.liebertonline.com/ten.

FIG. 4.

Comparative size of distal femurs. Note the significant differences in size between the distal femurs from a rat (left), a goat (center), and a human (right). The quarter and dime provide a reference to show the relative size of the condyles.