An Anterior Cruciate Ligament Failure Mechanism

Abstract

Background: Nearly three-quarters of anterior cruciate ligament (ACL) injuries occur as “noncontact” failures from routine athletic maneuvers. Recent in vitro studies revealed that repetitive strenuous submaximal knee loading known to especially strain the ACL can lead to its fatigue failure, often at the ACL femoral enthesis. Hypothesis: ACL failure can be caused by accumulated tissue fatigue damage: specifically, chemical and structural evidence of this fatigue process will be found at the femoral enthesis of ACLs from tested cadaveric knees, as well as in ACL explants removed from patients undergoing ACL reconstruction. Study Design: Controlled laboratory study. Methods: One knee from each of 7 pairs of adult cadaveric knees were repetitively loaded under 4 times–body weight simulated pivot landings known to strain the ACL submaximally while the contralateral, unloaded knee was used as a comparison. The chemical and structural changes associated with this repetitive loading were characterized at the ACL femoral enthesis at multiple hierarchical collagen levels by employing atomic force microscopy (AFM), AFM–infrared spectroscopy, molecular targeting with a fluorescently labeled collagen hybridizing peptide, and second harmonic imaging microscopy. Explants from ACL femoral entheses from the injured knee of 5 patients with noncontact ACL failure were also characterized via similar methods. Results: AFM–infrared spectroscopy and collagen hybridizing peptide binding indicate that the characteristic molecular damage was an unraveling of the collagen molecular triple helix. AFM detected disruption of collagen fibrils in the forms of reduced topographical surface thickness and the induction of ~30- to 100-nm voids in the collagen fibril matrix for mechanically tested samples. Second harmonic imaging microscopy detected the induction of ~10- to 100-µm regions where the noncentrosymmetric structure of collagen had been disrupted. These mechanically induced changes, ranging from molecular to microscale disruption of normal collagen structure, represent a previously unreported aspect of tissue fatigue damage in noncontact ACL failure. Confirmatory evidence came from the explants of 5 patients undergoing ACL reconstruction, which exhibited the same pattern of molecular, nanoscale, and microscale structural damage detected in the mechanically tested cadaveric samples. Conclusion: The authors found evidence of accumulated damage to collagen fibrils and fibers at the ACL femoral enthesis at the time of surgery for noncontact ACL failure. This tissue damage was similar to that found in donor knees subjected in vitro to repetitive 4 times–body weight impulsive 3-dimensional loading known to cause a fatigue failure of the ACL. Clinical Relevance: These findings suggest that some ACL injuries may be due to an exacerbation of preexisting hierarchical tissue damage from activities known to place larger-than-normal loads on the ACL. Too rapid an increase in these activities could cause ACL tissue damage to accumulate across length scales, thereby affecting ACL structural integrity before it has time to repair. Prevention necessitates an understanding of how ACL loading magnitude and frequency are anabolic, neutral, or catabolic to the ligament.

Learning From Failure

“…It has taken us more than 10 years to acquire data demonstrating that in fact ACL fatigue failure is a possibility along with direct evidence of the microdamage involved. In Chen et al, 2 we demonstrated that one can cause damage to accumulate at the molecular, cellular, and ultrastructural levels at the ACL femoral enthesis of cadavers under repetitive submaximal loading, and we also observed a similar damage signature in the femoral entheses of ACLs removed from living athletes at the time of their surgical repair. Savio Woo showed that the maximal tensile load that a healthy young adult ACL could withstand under 1 loading cycle is about 500 lbf.…”

Long-term Effect of a Single Subcritical Knee Injury: Increasing the Risk of Anterior Cruciate Ligament Rupture and Osteoarthritis

“…Repetitive loading has also been shown to cause fatigue failure of the ACL, with in vitro and in vivo studies of human joints identifying the femoral enthesis as a site commonly susceptible to disruption. 15 While repetitive loads were not applied to the joint in the current study, the femoral insertion was still identified as a site of histopathological remodeling that coincided with the temporal decline in ACL strength. This biological remodeling likely occurs in response to excessive loading at the time of injury, given that the femoral enthesis is a common site of failure in mouse models of intentional ACL rupture (ie, loading beyond subcritical thresholds).…”

Clinical Observations of Anterior Cruciate Ligament (ACL) Lesions in Patients with Chronic Fatigue

“…Some research has pointed that fatigue could cause acute ACL lesion [12][13][14][15][16][17][18][19][20][21][22][23] , but the de nition of ACL fatigue lesion has not been revealed completely from academic eld. Until 2013, Ashton-Miller 's biomechanical study based on knee model through donated human corpses has demonstrated that repetitive pressure-applying jump is likely to cause ACL fatigue damage, but Miller 's research is only limited in biomechanical eld, not involved with clinical research [24][25] . For two of the cases, arthroscopy surgery was performed and concluded that ACL fatigue lesion without trauma history manifested as ligament relaxation and partial femoral end damage.…”