Sex-Dependent Growth, Function, and Impact of Injury of the Porcine Anterior Cruciate Ligament

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URL: https://www.lib.ncsu.edu/resolver/1840.20/39938

Abstract

The anterior cruciate ligament (ACL) plays a crucial role in stabilizing the knee joint during athletic tasks. Concerningly, the incidence of pediatric ACL injuries is rapidly increasing. Age and sex influence injury rates, with females at a higher risk for ACL injury than males specifically during adolescence. However, there is a limited understanding of the factors driving these injury rates. Additionally, approximately one quarter of diagnosed ACL injuries are partial tears, which do not extend through the full thickness of the ligament and can be concentrated in either the anteromedial (AM) or posterolateral (PL) bundle of the ACL. Ideal treatment strategies for partial ACL injuries in young athletes remain contested due to a limited understanding of ACL maturation during skeletal growth and limited ability to perform large exploratory studies in the pediatric population. Preclinical models can help us understand these basic science questions and explore ACL injury treatments in skeletally immature subjects.

Therefore, the objective of this dissertation was to investigate the impact of age and sex on the structure and function of the ACL, and to assess the knee joint response to partial and complete ACL injury during skeletal growth in a porcine model. In this dissertation, we comprehensively evaluated the structure and biomechanical function of the ACL and its AM and PL bundles in male and female Yorkshire cross-breed pigs aged early youth to late adolescence. We showed that sex-differences in size and biomechanical function of the AM and PL bundles of the ACL emerge during adolescence and persisted after normalizing to bone size. Next, by evaluating the impact of injury in male and female joints across growth, we found that complete ACL injury led to major destabilization in all cases, but partial ACL injury led to minor destabilization which increased with age. In-vivo studies showed that even small destabilization led to long-term degenerative changes within the joint. ACL injury severity (partial or complete) and location (AM or PL bundle) impacted results, but grouped analyses indicated that degenerative changes were related to the extent of joint destabilization across all injury types. This work provides a fundamental basis for informing clinical treatments in young patients with partial and complete ACL tears.

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