Sex Influences the Biomechanical Outcomes of Anterior Cruciate Ligament Reconstruction in a Preclinical Large Animal Model

Abstract

Background: The risk of anterior cruciate ligament (ACL) injury is 2 to 10 times greater in women than men. While the effect of sex on injury risk is well established, its effects on surgical outcomes remain controversial.

Purpose/hypothesis: To investigate whether the biomechanical outcomes of ACL reconstruction are affected by sex using an established porcine model that displays similar sex-specific differences in knee anatomy and ligament structural properties to humans. The hypothesis was that there will be sex differences in ACL reconstruction outcomes with regard to the graft structural properties, knee laxity, and cartilage damage.

Study design: Controlled laboratory study.

Methods: A total of 41 adolescent Yucatan minipigs (23 male, 18 female) underwent unilateral ACL transection and ACL reconstruction using sex-matched bone-patellar tendon-bone allografts (with or without additional bioenhancement). Graft biomechanical and histological properties, knee laxity, and cartilage damage were assessed after 15 weeks. A 2-factor analysis of variance was used to investigate the effect of sex on all the measured outcomes after adjusting for the treatment effect.

Results: After 15 weeks of healing, female pigs had a significantly lower mean normalized graft yield load (by 18.5% ± 7.7%; P = .023) and linear stiffness (by 11.9% ± 5.6%; P = .043) compared with male pigs. Female pigs had significantly greater side-to-side differences in anteroposterior knee laxity at 30° (by 1.4 ± 0.6 mm; P = .028) and 90° (by 1.8 ± 0.8 mm; P = .032). Female pigs had a lower graft vascular density (by 0.8 ± 0.3 [analog scoring]; P = .021) with similar cellular and collagen-based histologic scores in both sexes (P > .6). Female pigs also had a significantly larger area of cartilage damage (by 43.3 ± 14.8 mm(2); P = .014) after conventional ACL reconstruction compared with their male counterparts.

Conclusion: Female pigs had significantly worse outcomes (ie, graft structural properties, knee laxity, and cartilage damage) compared with male pigs in this translational model after 15 weeks of healing.

Clinical relevance: These data suggest that further optimization of ACL injury treatments may be needed to accommodate each sex instead of using a "one fits all" approach to improve surgical outcomes, decrease incidence of reinjury, and decrease posttraumatic osteoarthritis risk after ACL reconstruction.

Keywords: anterior cruciate ligament; biomechanical outcomes; posttraumatic osteoarthritis; reconstruction; sex.

Figure 1

Schematics of the test fixtures used for (A) AP laxity and (B) tensile failure testing. For AP laxity testing, the knee flexion angle was prescribed, axial tibial rotation was constrained in the neutral position, and the translations in the coronal plane were unconstrained while the AP loads were prescribed. For tensile testing (B), the knee flexion angle was initially set at 30°. The tibia was mounted to the base of the MTS via a sliding X-Y platform while the femur was unconstrained to rotations so that the specimen could seek its own position to ensure that the load was distributed over the entire graft cross section (Adopted with permission from Fleming et al^, ).

Figure 2

Sex differences in normalized graft structural properties. The values were adjusted for the treatment effect and then mean±SEM are reported.

Figure 3

Sex differences in side-to-side differences in AP knee laxity. The values were adjusted for the treatment effect and then mean±SEM are reported.

Figure 4

Sex differences in graft histological scores. The values were adjusted for the treatment effect and then mean±SEM are reported.

Figure 5

Sex differences in macroscopic cartilage damage for animals undergoing conventional ACL reconstruction with allograft bone-patellar tendon-bone graft (Mean±SEM).