Biomechanics of the anterior cruciate ligament under simulated molecular degradation

Adouni, Malek; Gouissem, Afif; Khatib, Fadi Al; Eilaghi, Armin

doi:10.22203/ecm.v043a04

Cited by 8 publications

(8 citation statements)

References 41 publications

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“…All MD simulations were performed using LAMMPS molecular dynamics software [ 36 ] ( Fig 1 ). Additional details about the developed model can be found in the S1 File and our prior works [ 18 , 24 , 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

“…An accurate understanding of soft tissue failure initiation could be comprehended by simultaneously combining actual and extrapolated kinematics/kinetics measurements with a multiscale computation paradigm that links the molecular foundation of the soft tissue to the continuum level [ 3 , 18 ]. Therefore, a hybrid computational framework linking three different syntheses—molecular dynamics (MD), finite element analysis (FEA), and musculoskeletal modeling was developed.…”

Section: Introductionmentioning

confidence: 99%

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Knee joint biomechanics and cartilage damage prediction during landing: A hybrid MD-FE-musculoskeletal modeling

et al. 2023

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Understanding the mechanics behind knee joint injuries and providing appropriate treatment is crucial for improving physical function, quality of life, and employability. In this study, we used a hybrid molecular dynamics-finite element-musculoskeletal model to determine the level of loads the knee can withstand when landing from different heights (20, 40, 60 cm), including the height at which cartilage damage occurs. The model was driven by kinematics–kinetics data of asymptomatic subjects at the peak loading instance of drop landing. Our analysis revealed that as landing height increased, the forces on the knee joint also increased, particularly in the vastus muscles and medial gastrocnemius. The patellar tendon experienced more stress than other ligaments, and the medial plateau supported most of the tibial cartilage contact forces and stresses. The load was mostly transmitted through cartilage-cartilage interaction and increased with landing height. The critical height of 126 cm, at which cartilage damage was initiated, was determined by extrapolating the collected data using an iterative approach. Damage initiation and propagation were mainly located in the superficial layers of the tibiofemoral and patellofemoral cartilage. Finally, this study provides valuable insights into the mechanisms of landing-associated cartilage damage and could help limit joint injuries and improve training programs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Knee joint biomechanics and cartilage damage prediction during landing: A hybrid MD-FE-musculoskeletal modeling

et al. 2023

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“…As an essential structural component within the knee joint, the ACL determines the function and longevity of the entire knee structure. Previous studies have focused primarily on the mechanical properties of the ACL as an important stabilizer for knee joint motion [24] . KOA induced by ACL degeneration is believed to be caused by an imbalance in knee mechanics, which accelerates local cartilage wear and tear, thereby leading to an earlier onset of OA [25] .…”

Section: Discussionmentioning

confidence: 99%

Identification of anterior cruciate ligament fibroblasts and their contribution for knee osteoarthritis progression by single-cell analyses

Zhang

et al. 2023

Preprint

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Objective A better Understanding of the key regulatory cells in the anterior cruciate ligament (ACL), and their role and regulatory mechanisms in knee osteoarthritis (KOA) progression can facilitate the development of targeted treatment strategies for KOA. Methods The relationship between ACL degeneration and KOA was first explored using human ACL specimens and mouse models. Next, single-cell RNA sequencing (scRNA-seq) and single-cell detection of transposase accessible and chromatin sequencing (scATAC-seq) data were integrated to reveal the transcriptional and epigenomic landscape of ACL in normal and osteoarthritis (OA) states. Results Six cell populations were identified in the human ACL, among which were inflammation-associated fibroblasts (IAFs). Degeneration of the ACL during OA mechanically alters the knee joint homeostasis and influences the microenvironment by regulating inflammatory- and osteogenic-related factors, thereby contributing to the progression of KOA. Specifically, a IAF subpopulation identified in OA ACL was found to enhance the transcription and secretion of EGER via SOX5 upregulation, with consequent activation of the EGER–EGFR signaling pathway. These molecular events led to the upregulation of downstream inflammatory and osteogenic factors, and the downregulation of the extracellular matrix-associated factor, thereby leading to knee osteoid formation, cartilage degeneration, and OA progression. Conclusions In summary, this study identifies a novel subpopulation of fibroblasts in the ACL, which confirms the importance of the ACL in knee joint homeostasis and disease. Additionally, the specific mechanism by which these IAFs regulate KOA progression was uncovered, which provides new foundation for the development of targeted treatments for KOA.

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“…Ligaments mainly consist of water, cells, and extracellular matrix (ECM) components, including type-I collagen and elastin, which bind directly or indirectly via proteoglycans, laminin, and other adhesion molecules [ 8 , 9 ]. Collagen, which accounts for 85–90% of the ECM dry weight, as the major component of ligaments, provides them with moderate rigidity and viscoelasticity [ 10 ]. On the other hand, elastin accounts for approximately 10% of the dry weight of the ECM and is considered to render the ligaments extensible [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Elastin is responsible for the rigidity of the ligament under shear and rotational stress: a mathematical simulation study

Naya

Takanari

2023

J Orthop Surg Res

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Background An accurate understanding of the mechanical response of ligaments is important for preventing their damage and rupture. To date, ligament mechanical responses are being primarily evaluated using simulations. However, many mathematical simulations construct models of uniform fibre bundles or sheets using merely collagen fibres and ignore the mechanical properties of other components such as elastin and crosslinkers. Here, we evaluated the effect of elastin-specific mechanical properties and content on the mechanical response of ligaments to stress using a simple mathematical model. Methods Based on multiphoton microscopic images of porcine knee collateral ligaments, we constructed a simple mathematical simulation model that individually includes the mechanical properties of collagen fibres and elastin (fibre model) and compared with another model that considers the ligament as a single sheet (sheet model). We also evaluated the mechanical response of the fibre model as a function of the elastin content, from 0 to 33.5%. Both ends of the ligament were fixed to a bone, and tensile, shear, and rotational stresses were applied to one of the bones to evaluate the magnitude and distribution of the stress applied to the collagen and elastin at each load. Results Uniform stress was applied to the entire ligament in the sheet model, whereas in the fibre model, strong stress was applied at the junction between collagen fibres and elastin. Even in the same fibre model, as the elastin content increased from 0 to 14.4%, the maximum stress and displacement applied to the collagen fibres during shear stress decreased by 65% and 89%, respectively. The slope of the stress–strain relationship at 14.4% elastin was 6.5 times greater under shear stress than that of the model with 0% elastin. A positive correlation was found between the stress required to rotate the bones at both ends of the ligament at the same angle and elastin content. Conclusions The fibre model, which includes the mechanical properties of elastin, can provide a more precise evaluation of the stress distribution and mechanical response. Elastin is responsible for ligament rigidity during shear and rotational stress.

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Biomechanics of the anterior cruciate ligament under simulated molecular degradation

Cited by 8 publications

References 41 publications

Knee joint biomechanics and cartilage damage prediction during landing: A hybrid MD-FE-musculoskeletal modeling

Knee joint biomechanics and cartilage damage prediction during landing: A hybrid MD-FE-musculoskeletal modeling

Identification of anterior cruciate ligament fibroblasts and their contribution for knee osteoarthritis progression by single-cell analyses

Elastin is responsible for the rigidity of the ligament under shear and rotational stress: a mathematical simulation study

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