Biology subjects

Esrafilian, A.

Publications and source records attributed to Esrafilian, A..

4 recordsLinked to original sources

bioRxiv2024

Time-dependent computational model of post-traumatic osteoarthritis to estimate how mechanoinflammatory mechanisms impact cartilage aggrecan content

Degenerative musculoskeletal diseases like osteoarthritis can be initiated by joint injury. Injurious overloading-induced mechanical straining of articular cartilage and subsequent biological responses may trigger cartilage degradation. One early sign of degradation is loss of aggrecan content which is potentially accelerated near chondral lesions under physiological loading. Yet, the mechanoinflammatory mechanisms explaining time-dependent degradation in regions with disparate mechanical loading are unclear and challenging to assess with experiments alone. Here, we developed computational models unraveling potential mechanisms behind aggrecan content adaptation. Incorporating mechanical strain-driven cell damage and downstream proteolytic enzyme release, fluid flow-driven aggrecan depletion, and fluid pressure-stimulated regulation of aggrecan biosynthesis, the models agreed with experiments and exhibited 14%-points greater near-lesion aggrecan loss after 12 days of physiological loading compared to without loading. This significant advancement in mechanistic understanding incorporated into cartilage adaptation model can help in development and guidance of personalized therapies, such as rehabilitation protocols and tissue- engineered constructs.

bioengineering↗

bioRxiv2024

Joint and tissue mechanics in post-traumatic osteoarthritis: insights from the rat model

ObjectiveAltered mechanical loading is a known risk factor for osteoarthritis. Destabilization of the medial meniscus (DMM) is a preclinical gold standard model for post-traumatic osteoarthritis and is thought to induce instability and locally increased loading. However, the joint- and tissue-level mechanical environment underlying cartilage degeneration remains poorly documented. DesignUsing a custom multiscale modeling approach, we assessed joint and tissue biomechanics in rats undergoing sham surgery and DMM. High-fidelity experimental gait data were collected in a setup combining biplanar fluoroscopy and a ground reaction force plate. Knee poses and joint-level loading were estimated through musculoskeletal modeling, using bony landmarks, semi-automatically tracked via deep learning on fluoroscopic images, and ground reaction forces. A musculoskeletal model of the rat hindlimb was adapted to represent knee flexion-extension, valgus-varus, and internal-external rotation. The tissue-level cartilage mechanical environment was then spatially estimated, using the musculoskeletal modeling parameters as inputs into a dedicated finite element (FE) model of the rat knee, comprising cartilage and meniscal tissues. Experimental gait data and modeling workflows, including musculoskeletal models and FE meshes, are openly shared through a data repository. ResultsIn rats with DMM, the frontal plane knee pose was altered, yet there was no indication of joint-level overloading. Tissue-level mechanical cues typically linked with cartilage degeneration were not increased in the medial tibial cartilage, despite evidence of tissue structural changes. ConclusionDMM did not increase joint and tissue mechanical responses in the knee medial compartment, suggesting that mechanical loading alone does not explain the observed osteoarthritis-like structural changes.

bioengineering↗

bioRxiv2023

An Automated and Robust Tool for Musculoskeletal and Finite Element Modeling of the Knee Joint

ObjectiveTo develop and assess an automatic and robust knee musculoskeletal finite element (MSK-FE) modeling pipeline. MethodsMagnetic resonance images (MRI) were used to train nnU-Net networks for auto-segmentation of knee bones (femur, tibia, patella, and fibula), cartilages (femur, tibia, and patella), menisci, and major knee ligaments. Two different MRI sequences were used to broaden applicability. Next, we created MSK-FE models of an unseen dataset using two MSK-FE modeling pipelines: template-based and auto-meshing. MSK models had personalized knee geometries with multi-degree-of-freedom elastic foundation contacts. FE models used fibril-reinforced poroviscoelastic swelling material models for cartilages and menisci. ResultsVolumes of knee bones, cartilages, and menisci did not significantly differ (p>0.05) across MRI sequences. MSK models estimated secondary knee kinematics during passive knee flexion tests consistent with in vivo and simulation-based values from the literature. Between the template-based and auto-meshing FE models, estimated cartilage mechanics often differed significantly (p<0.05), though differences were <15% (considering peaks during walking), i.e., <1.5 MPa for maximum principal stress, <1 percentage point for collagen fibril strain, and <3 percentage points for maximum shear strain. ConclusionThe template-based modeling provided a more rapid and robust tool than the auto-meshing approach, while the estimated knee biomechanics were comparable. Nonetheless, the auto-meshing approach might provide more accurate estimates in subjects with distinct knee irregularities, e.g., cartilage lesions. SignificanceThe MSK-FE modeling tool provides a rapid, easy-to-use, and robust approach to investigating task- and person-specific mechanical responses of the knee cartilage and menisci, holding significant promise, e.g., in personalized rehabilitation planning.

bioengineering↗

bioRxiv2021

An EMG-assisted Muscle-Force Driven Finite Element Analysis Pipeline to Investigate Joint- and Tissue-Level Mechanical Responses in Functional Activities: Towards a Rapid Assessment Toolbox

Joint tissue mechanics (e.g., stress and strain) are believed to have a major involvement in the onset and progression of musculoskeletal disorders, e.g., knee osteoarthritis (KOA). Accordingly, considerable efforts have been made to develop musculoskeletal finite element (MS-FE) models to estimate highly-detailed tissue mechanics that predict cartilage degeneration. However, creating such models is time-consuming and requires advanced expertise. This limits these complex, yet promising MS-FE models to research applications with few participants and making the models impractical for clinical assessments. Also, these previously developed MS-FE models are not assessed for any activities other than the gait. This study introduces and validates a semi-automated rapid state-of-the-art MS-FE modeling and simulation toolbox incorporating an electromyography (EMG) assisted MS model and a muscle-force driven FE model of the knee with fibril-reinforced poro(visco)elastic cartilages and menisci. To showcase the usability of the pipeline, we estimated joint- and tissue-level knee mechanics in 15 KOA individuals performing different daily activities. The pipeline was validated by comparing the estimated muscle activations and joint mechanics to existing experimental data. Also, to examine the importance of EMG-assisted MS analyses, results were compared against outputs from the same FE models but driven by static-optimization-based MS models. The EMG-assisted MS-FE pipeline bore a closer resemblance to experiments, compared to the static-optimization-based MS-FE pipeline. More importantly, the developed pipeline showed great potentials as a rapid MS-FE analysis toolbox to investigate multiscale knee mechanics during different activities of individuals with KOA.

biophysics↗