The human anterior cruciate ligament: Sex differences in ultrastructure and correlation with biomechanical properties

Abstract

The purpose of this study was to investigate the existence of sex-based differences in the ultrastructural characteristics of the human anterior cruciate ligament (ACL) as the underlying cause of differences in the structural and mechanical properties between sexes. The ACL of six male and six female cadaveric donors were randomly chosen from a pool of 10 male and 10 female ACLs that had previously been tested for their structural and mechanical properties. Eighteen tissue samples from the distal, proximal, and middle sections of the anteromedial and posterolateral bundles were analyzed by transmission electron microscopy. Female ACLs exhibited both lower fibril concentration and lower percent area occupied by collagen fibrils ( p < 0.05) compared to males. There was also a difference in the fibril diameters ( p < 0.05); donor age, height, body mass, and body mass index contributed significantly to this difference. In females, ACL stiffness and modulus of elasticity were highly correlated to fibril concentration (r ¼ 0.96 and 0.97, respectively); in males ACL failure load and strength were highly correlated to percent area occupied by collagen (r ¼ 0.96 and 0.96, respectively). These differences in ultrastructure may underlie differences in ACL properties between sexes. The anterior cruciate ligament (ACL) is a multifascicular structure made up of two bundles. Its two-bundle structure and complex attachment to the femur and the tibia allow for one or both bundles to be functional (taut) in all possible knee positions. 1 ACL bundles are composed of collagen fibrils oriented mostly in the direction of loading. 2 Strocchi et al. 3 and Baek et al. 4 previously described the ultrastructural characteristics of the human ACL, including size distribution of the collagen fibrils, number of fibrils per unit area, and percent area occupied by collagen, as determined by transmission electron microscopy (TEM). These investigators suggested that changes or variations in ultrastructural characteristics are strictly related to functional requirements. 4,5 Recent studies showed that ACL mechanical, structural, and geometric characteristics are dependent on sex. 6,12 Female ACLs offer less resistance to deformation (are less stiff) and fail at lower loads compared to male ACLs. Furthermore, molecular studies identified sex differences in expression of collagen and matrix metalloproteinase genes that influence remodeling and turnover of structural elements in the ACL. 7 If ACL properties indeed reflect ultrastructure, and sex-based differences in ACL properties exist, then the ultrastructure of the male and female ACL should also differ. To date, sex-based ultrastructural differences have not been reported. Furthermore, the mechanical properties of the ACL have not been directly linked to its ultrastructure.We hypothesized that collagen fibril measurements, including average fibril diameter, number of fibrils per unit area, and percent area occupied by collagen, are different between sexes. We further hypothesized that A...

Hip extension, knee flexion paradox: A new mechanism for non-contact ACL injury

“…A female's smaller ACL size (Chandrashekar et al, 2005), lower ACL strength (Chandrashekar et al, 2006), and less-efficient ACL ultrastructure (Hashemi et al, 2008b) may collectively be a final disadvantage in leading to this injury. Indeed, additional study will be required to determine whether sex influences susceptibility to injury primarily by determining ACL size and strength or rather by affecting the likelihood that an injurious load will be applied.…”

ACL Research Retreat VII: An Update on Anterior Cruciate Ligament Injury Risk Factor Identification, Screening, and Prevention

“…111 After adjusting for age and anthropometric factors, the female ACL has less collagen fiber density (area of collagen fibers/total area of the micrograph) 112 and decreased mechanical properties, including strain at failure, stress at failure, and modulus of elasticity. 113 Females are also reported to have greater lateral and medial posterior-inferior tibial slopes, 114,115 reduced coronal tibial slopes, 114 taller femoral notch heights, and smaller femoral notch widths than males.…”

Repeated application of incremental landing impact loads to intact knee joints induces anterior cruciate ligament failure and tibiofemoral cartilage deformation and damage: A preliminary cadaveric investigation

“…Though our findings only revealed that the repeated application of incremental landing impact loads to intact male cadaveric specimens can induce ACL failure and tibiofemoral cartilage deformation and damage, we expect some differences in these outcomes for female specimens. Previous studies have shown that women displayed different ACL ultrastructure and biomechanical properties (Hashemi et al, 2008), and greater knee valgus during landing (Russell et al, 2006), compared to men; these differences are important risk factors for ACL failure. We therefore speculate that the application of our impact protocol to female cadaveric specimens in a physiological valgus position may potentially result in the occurrence of ACL failure at lower impact loads, and greater deformation and damage at lateral tibiofemoral cartilage compartments.…”