| 1. |
- Ebrahimi, Mohammadhossein, et al.
(författare)
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Associations of human femoral condyle cartilage structure and composition with viscoelastic and constituent-specific material properties at different stages of osteoarthritis
- 2022
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- The relationships between structure and function in human knee femoral cartilage are not well-known at different stages of osteoarthritis. Thus, our aim was to characterize the depth-dependent composition and structure (proteoglycan content, collagen network organization and collagen content) of normal and osteoarthritic human femoral condyle cartilage (n = 47) and relate them to their viscoelastic and constituent-specific mechanical properties that are obtained through dynamic sinusoidal testing and fibril-reinforced poroelastic material modeling of stress-relaxation testing, respectively. We characterized the proteoglycan content using digital densitometry, collagen network organization (orientation angle and anisotropy) using polarized light microscopy and collagen content using Fourier transform infrared spectroscopy. In the superficial cartilage (0–10 % of thickness), the collagen network disorganization and proteoglycan loss were associated with the smaller initial fibril network modulus - a parameter representing the pretension of the collagen network. Furthermore, the proteoglycan loss was associated with the greater strain-dependent fibril network modulus - a measure of nonlinear mechanical behavior. The proteoglycan loss was also associated with greater cartilage viscosity at a low loading frequency (0.005 Hz), while the collagen network disorganization was associated with greater cartilage viscosity at a high loading frequency (1 Hz). Our results suggest that proteoglycan loss and collagen network disorganization reduce the pretension of the collagen network while proteoglycan degradation also increases the nonlinear mechanical behavior of the collagen network. Further, the results also highlight that proteoglycan loss and collagen disorganization increase the viscosity of femoral cartilage, but their contribution to increased viscosity occurs in completely different loading frequencies.
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| 2. |
- Ebrahimi, Mohammadhossein, et al.
(författare)
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Elastic, Dynamic Viscoelastic and Model-Derived Fibril-Reinforced Poroelastic Mechanical Properties of Normal and Osteoarthritic Human Femoral Condyle Cartilage
- 2021
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 49:9, s. 2622-2634
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) degrades articular cartilage and weakens its function. Modern fibril-reinforced poroelastic (FRPE) computational models can distinguish the mechanical properties of main cartilage constituents, namely collagen, proteoglycans, and fluid, thus, they can precisely characterize the complex mechanical behavior of the tissue. However, these properties are not known for human femoral condyle cartilage. Therefore, we aimed to characterize them from human subjects undergoing knee replacement and from deceased donors without known OA. Multi-step stress-relaxation measurements coupled with sample-specific finite element analyses were conducted to obtain the FRPE material properties. Samples were graded using OARSI scoring to determine the severity of histopathological cartilage degradation. The results suggest that alterations in the FRPE properties are not evident in the moderate stages of cartilage degradation (OARSI 2-3) as compared with normal tissue (OARSI 0-1). Drastic deterioration of the FRPE properties was observed in severely degraded cartilage (OARSI 4). We also found that the FRPE properties of femoral condyle cartilage related to the collagen network (initial fibril-network modulus) and proteoglycan matrix (non-fibrillar matrix modulus) were greater compared to tibial and patellar cartilage in OA. These findings may inform cartilage tissue-engineering efforts and help to improve the accuracy of cartilage representations in computational knee joint models.
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| 3. |
- Florea, Cristina, et al.
(författare)
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A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time-dependent mechanical behavior of single cells
- 2017
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer Berlin/Heidelberg. - 1617-7959 .- 1617-7940. ; 16:1, s. 297-311
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Tidskriftsartikel (refereegranskat)abstract
- Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow-dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease.
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| 4. |
- Jahangir, Sana, et al.
(författare)
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Sensitivity of simulated knee joint mechanics to selected human and bovine fibril-reinforced poroelastic material properties
- 2023
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Ingår i: Journal of Biomechanics. - 0021-9290. ; 160
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Tidskriftsartikel (refereegranskat)abstract
- Fibril-reinforced poroviscoelastic material models are considered state-of-the-art in modeling articular cartilage biomechanics. Yet, cartilage material parameters are often based on bovine tissue properties in computational knee joint models, although bovine properties are distinctly different from those of humans. Thus, we aimed to investigate how cartilage mechanical responses are affected in the knee joint model during walking when fibril-reinforced poroviscoelastic properties of cartilage are based on human data instead of bovine. We constructed a finite element knee joint model in which tibial and femoral cartilages were modeled as fibril-reinforced poroviscoelastic material using either human or bovine data. Joint loading was based on subject-specific gait data. The resulting mechanical responses of knee cartilage were compared between the knee joint models with human or bovine fibril-reinforced poroviscoelastic cartilage properties. Furthermore, we conducted a sensitivity analysis to determine which fibril-reinforced poroviscoelastic material parameters have the greatest impact on cartilage mechanical responses in the knee joint during walking. In general, bovine cartilage properties yielded greater maximum principal stresses and fluid pressures (both up to 30%) when compared to the human cartilage properties during the loading response in both femoral and tibial cartilage sites. Cartilage mechanical responses were very sensitive to the collagen fibril-related material parameter variations during walking while they were unresponsive to proteoglycan matrix or fluid flow-related material parameter variations. Taken together, human cartilage material properties should be accounted for when the goal is to compare absolute mechanical responses of knee joint cartilage as bovine material parameters lead to substantially different cartilage mechanical responses.
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| 5. |
- Korhonen, Rami K., et al.
(författare)
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Multiscale In Silico Modeling of Cartilage Injuries
- 2023
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Ingår i: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 1402, s. 45-56
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Bokkapitel (refereegranskat)abstract
- Injurious loading of the joint can be accompanied by articular cartilage damage and trigger inflammation. However, it is not well-known which mechanism controls further cartilage degradation, ultimately leading to post-traumatic osteoarthritis. For personalized prognostics, there should also be a method that can predict tissue alterations following joint and cartilage injury. This chapter gives an overview of experimental and computational methods to characterize and predict cartilage degradation following joint injury. Two mechanisms for cartilage degradation are proposed. In (1) biomechanically driven cartilage degradation, it is assumed that excessive levels of strain or stress of the fibrillar or non-fibrillar matrix lead to proteoglycan loss or collagen damage and degradation. In (2) biochemically driven cartilage degradation, it is assumed that diffusion of inflammatory cytokines leads to degradation of the extracellular matrix. When implementing these two mechanisms in a computational in silico modeling workflow, supplemented by in vitro and in vivo experiments, it is shown that biomechanically driven cartilage degradation is concentrated on the damage environment, while inflammation via synovial fluid affects all free cartilage surfaces. It is also proposed how the presented in silico modeling methodology may be used in the future for personalized prognostics and treatment planning of patients with a joint injury.
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| 6. |
- Kosonen, Joonas P., et al.
(författare)
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Injury-related cell death and proteoglycan loss in articular cartilage : Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines
- 2023
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is a common musculoskeletal disease that leads to deterioration of articular cartilage, joint pain, and decreased quality of life. When OA develops after a joint injury, it is designated as post-traumatic OA (PTOA). The etiology of PTOA remains poorly understood, but it is known that proteoglycan (PG) loss, cell dysfunction, and cell death in cartilage are among the first signs of the disease. These processes, influenced by biomechanical and inflammatory stimuli, disturb the normal cell-regulated balance between tissue synthesis and degeneration. Previous computational mechanobiological models have not explicitly incorporated the cell-mediated degradation mechanisms triggered by an injury that eventually can lead to tissue-level compositional changes. Here, we developed a 2-D mechanobiological finite element model to predict necrosis, apoptosis following excessive production of reactive oxygen species (ROS), and inflammatory cytokine (interleukin-1)-driven apoptosis in cartilage explant. The resulting PG loss over 30 days was simulated. Biomechanically triggered PG degeneration, associated with cell necrosis, excessive ROS production, and cell apoptosis, was predicted to be localized near a lesion, while interleukin-1 diffusion-driven PG degeneration was manifested more globally. Interestingly, the model also showed proteolytic activity and PG biosynthesis closer to the levels of healthy tissue when pro-inflammatory cytokines were rapidly inhibited or cleared from the culture medium, leading to partial recovery of PG content. The numerical predictions of cell death and PG loss were supported by previous experimental findings. Furthermore, the simulated ROS and inflammation mechanisms had longer-lasting effects (over 3 days) on the PG content than localized necrosis. The mechanobiological model presented here may serve as a numerical tool for assessing early cartilage degeneration mechanisms and the efficacy of interventions to mitigate PTOA progression.
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| 7. |
- Mononen, Mika E, et al.
(författare)
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A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group's joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R(2) = 0.95, p < 0.05; experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0-2 years, p < 0.001) was followed by a slow or negligible degeneration (2-4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis.
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| 8. |
- Mononen, Mika E., et al.
(författare)
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New algorithm for simulation of proteoglycan loss and collagen degeneration in the knee joint : Data from the osteoarthritis initiative
- 2018
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266. ; 36:6, s. 1673-1683
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is a harmful joint disease but prediction of disease progression is problematic. Currently, there is only one modeling framework which can be applied to predict the progression of knee osteoarthritis but it only considers degenerative changes in the collagen fibril network. Here, we have developed the framework further by considering all of the major tissue changes (proteoglycan content, fluid flow, and collagen fibril network) occurring in osteoarthritis. While excessive levels of tissue stresses controlled degeneration of the collagen fibril network, excessive levels of tissue strains controlled the decrease in proteoglycan content and the increase in permeability. We created four knee joint models with increasing degrees of complexity based on the depth-wise composition. Models were tested for normal and abnormal, physiologically relevant, loading conditions in the knee. Finally, the predicted depth-wise compositional changes from each model were compared against experimentally observed compositional changes in vitro. The model incorporating the typical depth-wise composition of cartilage produced the best match with experimental observations. Consistent with earlier in vitro experiments, this model simulated the greatest proteoglycan depletion in the superficial and middle zones, while the collagen fibril degeneration was located mostly in the superficial zone. The presented algorithm can be used for predicting simultaneous collagen degeneration and proteoglycan loss during the development of knee osteoarthritis.
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| 9. |
- Notermans, Thomas, et al.
(författare)
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A numerical framework for mechano-regulated tendon healing-Simulation of early regeneration of the Achilles tendon
- 2021
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 17:2, s. 1008636-1008636
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Tidskriftsartikel (refereegranskat)abstract
- Mechano-regulation during tendon healing, i.e. the relationship between mechanical stimuli and cellular response, has received more attention recently. However, the basic mechanobiological mechanisms governing tendon healing after a rupture are still not well-understood. Literature has reported spatial and temporal variations in the healing of ruptured tendon tissue. In this study, we explored a computational modeling approach to describe tendon healing. In particular, a novel 3D mechano-regulatory framework was developed to investigate spatio-temporal evolution of collagen content and orientation, and temporal evolution of tendon stiffness during early tendon healing. Based on an extensive literature search, two possible relationships were proposed to connect levels of mechanical stimuli to collagen production. Since literature remains unclear on strain-dependent collagen production at high levels of strain, the two investigated production laws explored the presence or absence of collagen production upon non-physiologically high levels of strain (>15%). Implementation in a finite element framework, pointed to large spatial variations in strain magnitudes within the callus tissue, which resulted in predictions of distinct spatial distributions of collagen over time. The simulations showed that the magnitude of strain was highest in the tendon core along the central axis, and decreased towards the outer periphery. Consequently, decreased levels of collagen production for high levels of tensile strain were shown to accurately predict the experimentally observed delayed collagen production in the tendon core. In addition, our healing framework predicted evolution of collagen orientation towards alignment with the tendon axis and the overall predicted tendon stiffness agreed well with experimental data. In this study, we explored the capability of a numerical model to describe spatial and temporal variations in tendon healing and we identified that understanding mechano-regulated collagen production can play a key role in explaining heterogeneities observed during tendon healing.
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| 10. |
- Orozco, Gustavo A, et al.
(författare)
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A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait
- 2022
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity.
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| 11. |
- Orozco, Gustavo A., et al.
(författare)
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Crack propagation in articular cartilage under cyclic loading using cohesive finite element modeling
- 2022
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Ingår i: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- Severe joint injuries often involve cartilage defects that propagate after mechanical loading. The propagation of these lesions may contribute to the development of post-traumatic osteoarthritis (PTOA). However, the mechanisms behind their propagation remain unknown. Currently, no numerical predictive methods exist for estimating crack propagation in cartilage under cyclic loading, yet they would provide essential insights into crack growth in injured tissue after trauma. Here, we present a numerical approach to estimate crack propagation in articular cartilage under cyclic loading using a cohesive damage model. Four different material models for cartilage (hyperelastic, poro-hyperelastic, poro-hyper-viscoelastic, and fibril-reinforced poro-hyperelastic (FRPHE) with different collagen orientations) were implemented. Our numerical cohesive damage model was able to replicate the experimental crack length reported in the literature, showing greater crack length with an increasing number of loading cycles. Damage initiation stress (4.35–4.73 MPa) and fracture energy (0.97–1.55 N/mm) values obtained for the poro-hyperelastic, poro-hyper-viscoelastic, and parallel-FRPHE models were within the range of what has been reported previously. The crack growth predictions obtained by the FRPHE models showed the influence of anisotropy of the fibrillar matrix on the cartilage response. Our results indicate that our cohesive damage model could potentially be used to estimate the adverse conditions in injured soft tissue such as osteochondral lesions, menisci tears, or partial ligament ruptures under (ab)normal biomechanical scenarios.
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| 12. |
- Orozco, Gustavo A., et al.
(författare)
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Shear strain and inflammation-induced fixed charge density loss in the knee joint cartilage following ACL injury and reconstruction : A computational study
- 2022
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 40:7, s. 1505-1522
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Tidskriftsartikel (refereegranskat)abstract
- Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage–synovial fluid-interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies.
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| 13. |
- Paz, Alexander, et al.
(författare)
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A novel knee joint model in FEBio with inhomogeneous fibril-reinforced biphasic cartilage simulating tissue mechanical responses during gait : data from the osteoarthritis initiative
- 2023
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Ingår i: Computer Methods in Biomechanics and Biomedical Engineering. - : Informa UK Limited. - 1025-5842 .- 1476-8259. ; 26:11, s. 1353-1367
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Tidskriftsartikel (refereegranskat)abstract
- We developed a novel knee joint model in FEBio to simulate walking. Knee cartilage was modeled using a fibril-reinforced biphasic (FRB) formulation with depth-wise collagen architecture and split-lines to account for cartilage structure. Under axial compression, the knee model with FRB cartilage yielded contact pressures, similar to reported experimental data. Furthermore, gait analysis with FRB cartilage simulated spatial and temporal trends in cartilage fluid pressures, stresses, and strains, comparable to those of a fibril-reinforced poroviscoelastic (FRPVE) material in Abaqus. This knee joint model in FEBio could be used for further studies of knee disorders using physiologically relevant loading.
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| 14. |
- Simkheada, Tulashi, et al.
(författare)
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Comparison of constitutive models for meniscus and their effect on the knee joint biomechanics during gait
- 2023
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Ingår i: Computer Methods in Biomechanics and Biomedical Engineering. - : Informa UK Limited. - 1025-5842 .- 1476-8259. ; 26:16, s. 2008-2021
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical behavior of meniscus can be modeled using constitutive material models of varying complexity, such as isotropic elastic or fibril reinforced poroelastic (FRPE). However, the FRPE material is complex to implement, computationally demanding in 3D geometries, and simulation is time-consuming. Hence, we aimed to quantify the most suitable and efficient constitutive model of meniscus for simulation of cartilage responses in the knee joint during walking. We showed that simpler constitutive material models can reproduce similar cartilage responses to a knee model with the FRPE meniscus, but only knee models that consider orthotropic elastic meniscus can also reproduce meniscus responses adequately.
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| 15. |
- Turunen, Siru, et al.
(författare)
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The effect of collagen degradation on chondrocyte volume and morphology in bovine articular cartilage following a hypotonic challenge
- 2013
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer. - 1617-7959 .- 1617-7940. ; 12:3, s. 417-429
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Tidskriftsartikel (refereegranskat)abstract
- Collagen degradation is one of the early signs of osteoarthritis. It is not known how collagen degradation affects chondrocyte volume and morphology. Thus, the aim of this study was to investigate the effect of enzymatically induced collagen degradation on cell volume and shape changes in articular cartilage after a hypotonic challenge. Confocal laser scanning microscopy was used for imaging superficial zone chondrocytes in intact and degraded cartilage exposed to a hypotonic challenge. Fourier transform infrared microspectroscopy, polarized light microscopy, and mechanical testing were used to quantify differences in proteoglycan and collagen content, collagen orientation, and biomechanical properties, respectively, between the intact and degraded cartilage. Collagen content decreased and collagen orientation angle increased significantly (p < 0.05) in the superficial zone cartilage after collagenase treatment, and the instantaneous modulus of the samples was reduced significantly (p < 0.05). Normalized cell volume and height 20 min after the osmotic challenge (with respect to the original volume and height) were significantly (p < 0.001 and p < 0.01, respectively) larger in the intact compared to the degraded cartilage. These findings suggest that the mechanical environment of chondrocytes, specifically collagen content and orientation, affects cell volume and shape changes in the superficial zone articular cartilage when exposed to osmotic loading. This emphasizes the role of collagen in modulating cartilage mechanobiology in diseased tissue.
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