In this study, significant quantitative and qualitative differences between the human intra-articular structures of the knee and the animal species were found. Quantitatively, the human ACL was longer than the goat, dog and rabbit ACLs and wider than the dog and rabbit ACLs, whereas after normalization by the tibial plateau width, only the pig ACL showed a significantly greater length when compared to the human. The human PCL was wider than all of the animal PCLs, but only longer than goat, dog and rabbit PCLs. After normalization, only the PCL length of sheep and pig differed from the human. Previous studies have quantified the length and width of the human PCL as 38 mm in length and 13 mm in width 20
, measurements which are similar to those reported here of 40±7 mm and 14±5 mm, respectively. Only the cow knee had a notch width and medial meniscus length comparable to the human knee, whereas the medial and lateral meniscus width was closest to human in sheep, goats, pigs, and dogs. In prior studies of human menisci, the width of the mid-body of the medial meniscus and lateral meniscus as measured on MRI have been reported at 7.4 mm and 8.4 mm, respectively21
. Those measurements were consistent with those reported here (9.5±0.6 mm and 9.8±0.7 mm for the medial meniscus and lateral meniscus, respectively)22
. Qualitatively, the two bundles of the ACL (anteromedial and posterolateral bundles) and of the PCL (anterolateral and posteromedial) were not as well-defined in the human as they were in some of the animal knees. In the human and goat knees, the anterior insertion of the lateral meniscus adhered to the lateral side of the ACL which may have obscured the bundle separation in these knees. The cow, sheep, and pig knees had distinct bundles which were separated by the anterior insertion of the lateral meniscus. This is very important to consider when placing a tibial tunnel through the center of the ACL footprint while performing an ACL reconstruction on those animals, as the anterior horn of the lateral meniscus could potentially be injured. Likewise, a tibial tunnel placed posteriorly to the ACL insertion site in the goat model may also damage the anterior lateral meniscus insertion. The sheep PCL had two distinct tibial insertion sites, while all other species had only one.
Unlike the animal knees, the human knees had both horns of the lateral meniscus located more central than the medial meniscus attachments. The dog and rabbit knees did not have the anterior insertion of the lateral meniscus connecting to the ACL or separating the ACL bundles; however, it is certainly possible that these species do have cruciate bundles that are mechanically distinct even though they were not identified anatomically in this study. The posterior attachment of the lateral meniscus via the posterior menisco-femoral ligament is similar to that previously reported in dog and sheep knees23
. In that study, the menisco-femoral ligament was also present in both of these species, caudal to the PCL and more oblique, features noted in our study as well. None of the four human knees in this study had anterior intermeniscal ligaments, which have been well characterized in past cadaver studies24, 25
. However, in this study, the intermeniscal ligament was identified in three of the four dog knees. While the intermeniscal ligament in the human is supplemental to the bony anterior insertion sites of the menisci24
, this ligament was the only anterior attachment for the medial menisci in several of the dog knees in this study. Thus, the division of an intermeniscal ligament in the dog model may destabilize the medial meniscus as the knee does not have separate bony attachments for these structures. In a prior study about the anterior insertion of the human medial meniscus, the insertion site was found to have four variations. Type I insertions were located in the flat intercondylar region of the tibial plateau; Type II occurred on the downward slope from the medial articular plateau to the intercondylar region; Type III occurred on the anterior slope of the tibial plateau; there was no firm bony insertion of the anterior horn in Type IV26
. In our examination of four human knees, all the knees had Type I insertions, as did all the animal knees, with the exception of several of the dog knees which had a Type IV insertion. The variability in the insertion site anatomy in the animal species and humans may thus be important in translational studies of medial meniscus pathology.
Our measurements of the passive range of motion () of all knees show an inherent functional difference of the knees of the quadruped animal models compared to the human knee. All animals had a physiological limit of extension at about 40° to the neutral 0° axis in extension of the femur shaft (only rabbit knees were significantly more extendable to 22°). Although this significant difference in the range of motion occurs in all the common animal models for the knee joint and therefore is less of a factor when determining the optimal animal model for the human knee, it is crucial to keep this difference in mind when translating animal data to the human case.
Limitations of the study were the exclusive study of female specimens. While this selection bias prevented our contributing to the known gender-based differences in human knee anatomy, biomechanics, and cell biology27, 28
, it likely did result in a reduction of variance. Given the relatively high prevalence of knee injuries and specifically ACL ruptures in women compared to men3
was another reason to study the female knee. Another limitation in our study is the small number of specimens in each of the seven groups. A reliable statement can be given for the statistically significant comparisons, whereas not all non-significant comparisons have a power >80% and allow a correct interpretation. Apart from the specific limitations of this study, a general concern is the use of quadruped animals as knee models for the bipedal human, particularly given their range of motion differences noted in this study.
The disappearance of many of the observed differences in the cruciate and meniscal anatomy after normalization with the tibial plateau width suggests an overall conservation of relative size among species for the cruciates and menisci. Nonetheless, differences in the absolute size of the structures exist, which results in considerable changes in the load and shear the intra-articular structures are subjected to.
The overview in evaluates these characteristics, and can act as a guideline for choosing the right model for a certain structure. Sheep and cow specimens were the best match for the human ACL in size and proportion, but had their tibial ACL insertion split by the anterior lateral meniscus, whereas the goat ACL was shorter than the human ACL, but had a similar tibial insertion site. Based on anatomy alone, sheep, cows and goats may therefore make the best models for ACL injury treatment.
Animal Model Selection Guide illustrates levels of structural resemblance to the human anatomy
Interestingly, there was less conservation of PCL dimensions among the species studied. Only the cow PCL was comparable to the human PCL in absolute length, normalized values, and anatomy of the insertion sites, whereas the human PCL was significantly wider than all of the animal specimens. This may be attributed to differences in the range of motion of bipeds compared to quadrupeds. Since the PCL prevents the knee from overextending, it might have to sustain a higher load in the human knee at full extension, in comparison to the quadruped knees which are limited in their extension ().
The size and proportion of the human medial meniscus was most similar to the sheep and goat specimens. The human lateral meniscus was most similar in size to the sheep, goat and pig specimens; however, the anatomy of the tibial insertion sites of the lateral meniscus in the goat was most comparable to that of the human knee. Considering both the medial and lateral meniscus, the animal model with the closest anatomy to the human knee was the goat.