The use of sheep has not been widely utilized for the study of PTA; however, sheep may provide advantages because of their large joint size, which allows for the analysis of biochemical and biomechanical measures that may not be able to be performed in human subjects [39–41]. As with other large animals, sheep can readily undergo arthroscopic surgery and MRI observation, allowing for more direct translation of studies to the clinic. However, there are limited reagents and antibodies available, and until recently, a limited mapped genome for sheep, making it difficult for genetic studies [1–3]. Furthermore, their large size is a disadvantage in testing novel pharmacologic interventions. Most studies utilizing the ACL-T model in sheep have focused on radiographic tracking and kinematics of PTA. O’Brien and coworkers examined the effects of immediate reconstruction of the transected ACL on cartilage degeneration and osteophyte formation [41], while Atarod and coworkers examined the kinematic loads placed on soft tissue after ACL-T in the sheep [39]. A summary of the use of ovine ACL-T models is in Table 6.3 below.

Neuromuscular control has been extensively studied in cats, as well as muscle mechanics and locomotion [42]. Logically, cats would be well suited to study interventions towards musculoskeletal diseases, such as PTA that results from an ACL-T injury. Cats are advantageous to use because of their large size and known genome. However, like dogs, cats can be costly to house during experiments, and public perception and their role as companion animals discourage the use of cats for research [1–3].

Herzog and coworkers first studied the effect of ACL-T in cats on hindlimb loading and changes in articular cartilage [42]. Khalsa and coworkers studied the effect of severing the nerves associated with the joint capsule after ACL-T [43]. Herzog and coworkers monitored cats for a year, using force testing plates and radiographs to track kinematic and radiographic changes due to OA [44, 45]. Boyd and coworkers studied the changes to the periarticular bone as a result of ACL-T, while Clark and coworkers studied the adaptive response of cartilage after ACL-T [46, 47]. A summary of the studies utilizing feline ACL-T models follow in Table 6.4.

Rabbits have been a popular model for use with both ACL-T and meniscus injury models because of their low spontaneous joint degeneration, large joint size, and ease in use for testing new therapeutic agents. Rabbits preferentially load their lateral side, unlike rodents, and have the capability to spontaneous regenerate transected menisci with fibrous tissue, which can cause disadvantages for some studies. Similarly, rabbits have altered joint biomechanics, potentially resulting in a change in disease pathology compared to what may be expected in other animals. However, rabbits have been widely used as a model for OA because they form lesions similar to those seen in clinical OA [1–3].

The ACL-T model has been used in rabbits to study many aspects of PTA development. Studies have examined articular cartilage and meniscus properties [48–50], gene expression and surface receptors [51–53], osteophytes [54], bone properties [55, 56], and imaging techniques [57, 58]. The rabbit ACL-T model has also been used to test out therapeutics, such as HA therapy [59] and oral glucosamine supplements [60]. Furthermore, one study compared surgically induced ACL-T versus a blunt trauma ACL-T, which closely resembles clinical ACL-T in humans [61]. Studies using rabbit models of ACL-T are summarized in Table 6.5.