Validation of Porcine Knee as a Sex-specific Model to Study Human Anterior Cruciate Ligament Disorders

Abstract

Background Animal models have long been considered an important modality for studying ACL injuries. However, to our knowledge, the value of these preclinical models to study sex-related phenomena associated with ACL injury and recovery has not been evaluated. Questions/purposesWe asked whether (1) prominent anatomic and (2) biomechanical factors differ between female and male porcine knees, particularly those known to increase the risk of ACL injury. Methods Eighteen intact minipig knees (nine males, nine females) underwent MRI to determine the femoral bicondylar width, intercondylar notch size (width, area and index), medial and lateral tibial slope, ACL size (length, cross-sectional area, and volume), and medial compartment tibiofemoral cartilage thickness. AP knee laxity at 30°, 60°, and 90°flexion and ACL tensile structural properties were measured using custom-designed loading fixtures in a universal tensile testing apparatus. Comparisons between males and females were performed for all anatomic and biomechanical measures. The findings then were compared with published data from human knees. Results Female pigs had smaller bicondylar widths (2.9 mm, ratio = 0.93, effect size = À1.5) and intercondylar notches (width: 2.0 mm, ratio = 0.79, effect size = À2.8; area: 30.8 mm 2 , ratio = 0.76, effect size = 2.1; index: 0.4, ratio = 0.84, effect size = À2.0), steeper lateral tibial slope (4.3°, ratio = 1.13, effect size = 1.1), smaller ACL (length: 2.7 mm, ratio = 0.91, effect size = 1.1; area: 6.8 mm 2 , ratio = 0.74, effect size = À1.5; volume: 266.2 mm 3 , ratio = 0.68, effect size = À1.5), thinner medial femoral cartilage (0.4 mm, ratio = 0.8, effect size = À1.1), lower ACL yield load (275 N, ratio = 0.81, effect size = À1.1), and greater AP knee laxity at 30°( 0.7 mm, ratio = 1.32, effect size = 1.1) and 90°(0.5 mm, ratio = 1.24, effect size = 1

Biomechanical Outcomes of Bridge-enhanced Anterior Cruciate Ligament Repair Are Influenced by Sex in a Preclinical Model

“…However, similar anatomical and biomechanical features between pigs and humans have been noted in terms of biomechanics of the knee, hematology, and wound healing [11,45,58]. Moreover, the porcine large animal model has been previously shown to be a valid surrogate model for the human knee in the study of sex disparities thought to increase risk for ACL injury [30]. The investigation was conducted on juvenile, skeletally immature pigs.…”

“…This large animal model has been widely used in preclinical studies of ACL surgery [18-21, 27, 33, 35-37, 54, 55] and has recently been validated as a sex-specific large animal surrogate model to study the human knee [30]. The bridge-enhanced ACL repair procedures were performed using an absorbable suture stent (Vicryl 1 ; Ethicon Inc, Somerville, NJ, USA; n = 17) on one hindlimb and using a nonabsorbable suture stent (Ethibond; Ethicon Inc; n = 17) on the other hindlimb.…”

“…Thus, the current study was designed (1) to investigate the effect of sex on biomechanical outcomes of bridgeenhanced ACL repair; and (2) to determine if suture type (absorbable versus nonabsorbable) used to repair the torn ACL can alleviate the potential sex discrepancies in measured outcomes after 15 weeks of healing in a wellestablished porcine model with similar sex-specific knee anatomical and biomechanical properties as the human knee [30]. We hypothesized that there are sex differences in the biomechanical outcomes of bridge-enhanced ACL repair with lower ACL structural properties and greater AP knee laxity in females than males and that the choice of suture type used to repair the torn ACLs would affect the observed sex differences in measured biomechanical outcomes.…”

Comparison of Acute Histologic and Biomechanical Effects of Radiofrequency Ablation and Cryoablation on Periarticular Structures in a Swine Model

“…Another limitation of the present study design is that these perijoint tissues were directly targeted in a perpendicular fashion, thereby representing a worstcase scenario, which may not accurately portray indirect nontarget ablation that is more likely to occur in actual clinical practice. Finally, as the sex of the animals used in this study was unknown, the size and thickness of ligament, tendon, and cartilage may vary, which can affect mechanical properties of samples (32).…”

Novel technique for evaluation of knee function continuously through the range of flexion

“…Eight fresh-frozen skeletally mature porcine knees were used in this study (Boguszewski et al, 2011;Fuss, 1991;Kiapour et al, 2015;Xerogeanes et al, 1998). Each specimen was screened for bony abnormalities and osteoarthritis using a Fluoroscan Insight 2 mini-C-arm (Hologic Inc., Bedford, MA).…”