Large Animal Models for Anterior Cruciate Ligament Research

Abstract

Large animal (non-rodent mammal) models are commonly used in ACL research, but no species is currently considered the gold standard. Important considerations when selecting a large animal model include anatomical differences, the natural course of ACL pathology in that species, and biomechanical differences between humans and the chosen model. This article summarizes recent reports related to anatomy, pathology, and biomechanics of the ACL for large animal species (dog, goat, sheep, pig, and rabbit) commonly used in ACL research. Each species has unique features and benefits as well as potential drawbacks, which are highlighted in this review. This information may be useful in the selection process when designing future studies.

Remnants-preserving ACL reconstruction using direct tendinous graft fixation: a new rat model

“…Surprisingly, in the IT group, at 12 weeks, lameness was not detected on visual gait analysis (further corroborated by patellar BMD ratios between left operated and right non-operated knees approximating 1) and Lachman tests were negative in most of the knees, despite a more severe amyotrophy, joint effusion, and cartilage degeneration in that group. Complete resolution of lameness by 12 weeks after ACL transection has indeed already been reported in large animal models experiments, based on visual gait and force platform analysis, and suspected to be due to prey-related behaviors, in which visible lameness could confer a survival disadvantage, and/or to muscular compensation of the knee instability, but the latter hypothesis is nevertheless not corroborated by the muscular amyotrophy observed in the IT group of the present study [46,47]. Another explanation would be that both visual gait analysis and BMD evaluated 12 weeks postoperatively may be insufficient to characterize functional outcome in animals with isolated ACL section, which, as recently suggested, should be assessed in animal experiments using more clinically representative functional tests, but these are hardly applicable to animal models, for anatomical and animal compliancy reasons [16].…”

A Translational Porcine Model for Human Cell–Based Therapies in the Treatment of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Injury

“…10 As a result of the larger-caliber knee joint and the high prevalence of naturally occurring ACL injuries in dogs, the canine ACL injury model gained popularity as a large animal translational model of degenerative joint disease. One reason for this was the increased posterior tibial slope (~24°) 5 of the canine tibia relative to humans, which causes abnormal biomechanical properties likely contributing to accelerated progression of degenerative joint disease. The canine model does, however, have 2 significant limitations: cartilage thickness significantly less than that of humans and ethical considerations.…”

Decellularized porcine xenograft for anterior cruciate ligament reconstruction

“…Sheep are a recognized model for ACL reconstruction due to similarities between the stifle joint and the human knee, 15 - 17 and were chosen because their size and tibial plateau width allow human-sized tendons and fixation devices to be used. 18 A total of 12 skeletally mature female mule sheep were included, aged between two and three years old and weighing between 75 kg and 85 kg. Unilateral single-bundle ACL reconstruction was performed using pSFT scaffolds manufactured using previously described methods.…”