Abstract / Summary
Abstract Background ACL rupture is a common, debilitating injury in young, active individuals. Some individuals sustain ACL injury while others do not, despite similar activity exposure. Young, active females have more than twice the ACL injury risk of males. Interactions among the knee’s complex three-dimensional (3D) articular shapes may govern how multiplanar loads implicated in noncontact ACL injury are transmitted across the joint and routed through the ACL. However, whether the 3D knee shape–ACL loading relationship explains ACL injury susceptibility and sex-disparity in risk remains unknown. Methods We integrated a high throughput, subject-specific, physics-based modeling framework with a cohort of 168 young, active individuals, including equal numbers with and without acute ACL injury. We isolated 3D knee shape’s contribution to ACL loading using a standardized loading condition reflecting the clinical pivot shift examination, with ligament properties held constant across individuals. Results We show that 3D knee shape drives increased ACL force in ACL-injured individuals within each sex and in females compared to males. These differences are amplified after scaling ACL force by ACL cross-sectional area. Coupled internal tibial rotation mediates increased ACL loading in both sexes, and anterior tibial translation contributes additionally in females. Conclusions These findings identify that 3D knee shape drives ACL loading through coupled motions, providing mechanistic insight into ACL injury susceptibility and sex disparity in risk. This work establishes a foundation for incorporating subject-specific knee shape into emerging digital twin approaches for individualized knee mechanics assessments, risk stratification, injury prevention, and personalized ACL surgeries and rehabilitation.