Extracellular matrix content of ruptured anterior cruciate ligament tissue (original) (raw)

Anterior Cruciate Ligament Biology and Its Relationship to Injury Forces

Orthopedic Clinics of North America, 2006

The anterior cruciate ligament (ACL) is one of primary stabilizers of the knee, and disruption of this ligament is three to ten times more common in female athletes than male athletes who participate in the same sports at the same level of competition . These knee injuries are a growing cause for concern because of the association with earlyonset, posttraumatic osteoarthritis after severe ligament tears. Despite an abundance of theories about why female athletes are more susceptible to this injury and proposed neuromuscular training programs designed to protect the knee, no definitive causal link has been found among mechanisms of injury, sex, and ACL rupture.

The Role of Proteoglycans in the Viscoelastic Behaviour of the Anterior Cruciate Ligament

SSRN Electronic Journal, 2021

The contribution of proteoglycans (PGs) to the viscoelasticity of soft tissues such as ligaments is highly debated in current literature. To date, there is limited information on the mechanical role of PGs to the anterior cruciate ligament (ACL) in the knee joint which is both highly susceptible to injuries and contains higher PGs content compared to the collateral ligaments. This is the first study to collectively investigate the contribution of PGs to key viscoelastic characteristics (strain-rate dependency, recovery, hysteresis, creep and stress-relaxation) in the knee joint femur-ACL-tibia complex. Femur-ACL-tibia complexes (n=6 pairs) were harvested from disease-free canine knee joints and categorised into control and PGs-reduced groups. Specimens were preconditioned and cyclically loaded to 9.9 N at 0.1, 1 and 10%/min strain-rates followed by creep and stressrelaxation tests. Low tensile loads were applied to focus on the toe-region of the stress-strain curves where the non-collagenous extracellular matrix components are believed to take effect. Subsequently biochemical assays were performed on the ACLs to determine PGs and water content. Reduced PGs content in the ACLs significantly increased stress-relaxation (p<0.05) while it significantly decreased recovery (p< 0.01) and creep (p< 0.05). However, PGs had no effect on the stress-strain behaviour and hysteresis of the ACLs. The current study shows that altering PGs content can lead to changes in ACL viscoelasticity, which may predispose to injury and eventually leading to knee joint osteoarthritis.

The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics

2021

1Osteoarthritis (OA) is a whole joint disease that affects all knee joint tissues. Ligaments, a matrix-rich connective tissue, play an important mechanical function that stabilises the knee joint and yet their role in OA is not well studied. Recent studies have shown that ligament extracellular matrix (ECM) structure is compromised in the early stages of OA, but it remains unclear how this affects ligament function and biomechanics. In this study, the aim was to investigate the structural, cellular and viscoelastic changes in the anterior cruciate ligament (ACL) in a murine non-invasive post-traumatic OA (PTOA) model. Non-invasive mechanical loading of the knee joint of C57BL/6J mice (10-week-old) was used as a PTOA model. Knee joints were analysed for joint space mineralisation and the ACLs were assessed with histology and mechanical testing. PTOA knee joints had a 33-46% increase in joint space mineralisation and PTOA knee joint ACLs exhibited ECM modifications, including collagen...

Histological and cellular evaluation of anterior cruciate ligament

The Knee, 2020

Background: We hypothesized that the torn anterior cruciate ligament (ACL) demonstrates a great healing response after initial trauma and has competent cells leading to the healing but differs in its response based on the type of tear and duration of injury. This study aimed to evaluate the histological and cellular responses to the injured ACL. Methods: Fifty-two tissue samples from the ACL were harvested from patients undergoing arthroscopy. Detailed histological and cellular examinations were performed for ligament angiogenesis, fibrocytes, and synovial tissue infiltration. We compared the cellular response to injury in partially and completely ruptured ACLs. The duration of ACL injury and its response to cellular characteristics were also examined. Immunohistochemical studies using cluster of differentiation 34 (CD34) staining was used to evaluate endothelial cells and fibrocytes. Results: We found a significantly higher density of synovial and ligament angiogenesis and fibrocytes at the torn end of ACL (Mann-Whitney, P < 0.050). Numerous fibrocytes were identified in complete ACL tears versus partial tears (Mann-Whitney = 0.020). Increased cellular proliferation was identified at the ruptured end of ACL remnant (Kruskal-Wallis, P < 0.050). The cellular proliferation of ruptured ACL decreased after 12 months. Conclusions: Based on our findings of the time-dependent decrease in the cellular response at the torn ends of the ACL, we recommend early intervention, preservation of the ACL remnant, and primary ACL repair or augmented reconstruction.

An Anterior Cruciate Ligament Failure Mechanism

American Journal of Sports Medicine, 2019

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

Immature animals have higher cellular density in the healing anterior cruciate ligament than adolescent or adult animals

Journal of Orthopaedic Research, 2010

There has been recent interest in the biologic stimulation of anterior cruciate ligament (ACL) healing. However, the effect of age on the ability of ligaments to heal has not yet been defined. In this study, we hypothesized that skeletal maturity would significantly affect the cellular and vascular repopulation rate of an ACL wound site. Skeletally Immature (open physes), Adolescent (closing physes), and Adult (closed physes) Yucatan minipigs underwent bilateral ACL transection and suture repair using a collagen-platelet composite. The response to repair was evaluated histologically at 1, 2, and 4 weeks. All three groups of animals had completely populated the ACL wound site with fibroblasts at 1 week. The Immature animals had a higher cellular density in the wound site than the Adult animals at weeks 2 and 4. Cells in the Immature ligament wounds were larger and more ovoid than in the Adult wounds. There were no significant differences in the vascular density in the wound site. Animal age had a significant effect on the density of cells populating the ACL wound site. Whether this observed cellular difference has an effect on the later biomechanical function of the repaired ACL requires further study.

Biochemical and Structural Alterations in Skeletal Muscle Following ACL Injury: A Narrative Review

Australian International Academic Centre, 2020

Background: Anterior cruciate ligament (ACL) injuries are some of the most common knee injuries that occur in the US, accounting for around 200,000 documented cases per year. Varying levels of severity can determine whether surgery is required or if physical therapy will suffice. One of the most common complications for patients is that there is significant atrophy of the impacted limb. Yet, there has not been definitive proof explaining this mechanism. Objective: The primary goal for this review was to examine some of the biochemical differences that tend to occur within and surrounding an ACL injury and the mechanisms involved in skeletal muscle atrophy and regenerative capabilities. Outcome: Multiple studies have found a connection between time spent inactive from the injury and the percentage of retained muscle after exercising again. Among decreases in muscle mass and muscle volume changes, analyses have also revealed alterations in alpha-2 macroglobulin, myostatin, heat shock protein-72, mechano GF-C24E, synovial fluid, and histochemical alterations in collagen and cartilaginous states which all seem to be primary factors in regulating effectiveness and speed of recovery from ACL injury. Conclusion: the influx of various cytokines as a response to the initial injury in relation to inflammation change the chemical and physical environment of the knee, making recovery significantly more difficult and time-consuming. Timing of injury, surgery, and reinitiation of movement after surgery are very important factors that can minimize overall damage and reduce recovery time.