Publications by authors named "Rami K Korhonen"

97 Publications

Guide to mechanical characterization of articular cartilage and hydrogel constructs based on a systematic in silico parameter sensitivity analysis.

J Mech Behav Biomed Mater 2021 Aug 24;124:104795. Epub 2021 Aug 24.

Soft Tissue Biomechanics Group, Biomechanics Division, Mechanical Engineering Department, KU Leuven, Leuven, Belgium.

Osteoarthritis is a whole joint disease with cartilage degeneration being an important manifestation. Tissue engineering treatment is a solution for repairing cartilage defects by implantation of chondrocyte-laden hydrogel constructs within the defect. In silico models have recently been introduced to simulate and optimize the design of these constructs. These models require accurate knowledge on the mechanical properties of the hydrogel constructs and cartilage explants, which are challenging to obtain due to their anisotropic structure and time-dependent behaviour. We performed a systematic in silico parameter sensitivity analysis to find the most efficient unconfined compression testing protocols for mechanical characterization of hydrogel constructs and cartilage explants, with a minimum number of tests but maximum identifiability of the material parameters. The construct and explant were thereby modelled as porohyperelastic and fibril-reinforced poroelastic materials, respectively. Three commonly used loading regimes were simulated in Abaqus (ramp, relaxation and dynamic loading) with varying compressive strain magnitudes and rates. From these virtual experiments, the resulting material parameters were obtained for each combination using a numerical inverse identification scheme. For hydrogels, maximum sensitivity to the different material parameters was found when using a single step ramp loading (20% compression with 10%/s rate) followed by 15 min relaxation. For cartilage explants, a two-stepped ramp loading (10% compression with 10%/s rate and 10% compression with 1%/s rate), each step followed by 15 min relaxation, yielded the maximum sensitivity to the different material parameters. With these protocols, the material parameters could be retrieved with the lowest amount of uncertainty (hydrogel: < 2% and cartilage: < 6%). These specific results and the overall methodology can be used to optimize mechanical testing protocols to yield reliable material parameters for in silico models of cartilage and hydrogel constructs.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104795DOI Listing
August 2021

Functional and structural properties of human patellar articular cartilage in osteoarthritis.

J Biomech 2021 Jul 12;126:110634. Epub 2021 Jul 12.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Changes in the fibril-reinforced poroelastic (FRPE) mechanical material parameters of human patellar cartilage at different stages of osteoarthritis (OA) are not known. Further, the patellofemoral joint loading is thought to include more sliding and shear compared to other knee joint locations, thus, the relations between structural and functional changes may differ in OA. Thus, our aim was to determine the patellar cartilage FRPE properties followed by associating them with the structure and composition. Osteochondral plugs (n = 14) were harvested from the patellae of six cadavers. Then, the FRPE material properties were determined, and those properties were associated with proteoglycan content, collagen fibril orientation angle, optical retardation (fibril parallelism), and the state of OA of the samples. The initial fibril network modulus and permeability strain-dependency factor were 72% and 63% smaller in advanced OA samples when compared to early OA samples. Further, we observed a negative association between the initial fibril network modulus and optical retardation (r = -0.537, p < 0.05). We also observed positive associations between 1) the initial permeability and optical retardation (r = 0.547, p < 0.05), and 2) the initial fibril network modulus and optical density (r = 0.670, p < 0.01).These results suggest that the reduced pretension of the collagen fibrils, as shown by the reduced initial fibril network modulus, is linked with the loss of proteoglycans and cartilage swelling in human patellofemoral OA. The characterization of these changes is important to improve the representativeness of knee joint models in tissue and cell scale.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110634DOI Listing
July 2021

High-resolution infrared microspectroscopic characterization of cartilage cell microenvironment.

Acta Biomater 2021 Aug 5. Epub 2021 Aug 5.

Department of Applied Physics, University of Eastern Finland, POB 1627, 70211 Kuopio, Finland.

The lateral resolution of infrared spectroscopy has been inadequate for accurate biochemical characterization of the cell microenvironment, a region regulating biochemical and biomechanical signals to cells. In this study, we demonstrate the capacity of a high-resolution Fourier transform infrared microspectroscopy (HR-FTIR-MS) to characterize the collagen content of this region. Specifically, we focus on the collagen content in the cartilage cell (chondrocyte) microenvironment of healthy and osteoarthritic (OA) cartilage. Human tibial cartilage samples (N = 28) were harvested from 7 cadaveric donors and graded for OA severity (healthy, early OA, advanced OA). HR-FTIR-MS was used to analyze the collagen content of the chondrocyte microenvironment of five distinct zones across the tissue depth. HR-FTIR-MS successfully showed collagen content distribution across chondrocytes and their environment. In zones 2 and 3 (10 - 50% of the tissue thickness), we observed that collagen content was smaller (P < 0.05) in early OA compared to the healthy tissue in the vicinity of cells (pericellular region). The collagen content loss was extended to the extracellular matrix in advanced OA tissue. No significant differences in the collagen content of the chondrocyte microenvironment were observed between the groups in the most superficial (0-10%) and deep zones (50-100%). HR-FTIR-MS revealed collagen loss in the early OA cartilage pericellular region before detectable changes in the extracellular matrix in advanced OA. HR-FTIR-MS-based compositional assessment enables a better understanding of OA-related changes in tissues. This technique can be used to identify new disease mechanisms enabling better intervention strategies. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) is the most common degenerative joint disease causing pain and disability. While significant progress has been made in OA research, OA pathogenesis is still poorly understood and current OA treatments are mainly palliative. This study demonstrates that high-resolution FTIR microspectroscopy (HR-FTIR-MS) can characterize OA-induced compositional changes in the cell microenvironment (pericellular matrix) during the early disease stages before tissue changes in the extracellular matrix become apparent. This technique may further enable the identification of new OA mechanisms and improve our current understanding of OA pathogenesis, thus, enabling the development of better treatment methods.
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http://dx.doi.org/10.1016/j.actbio.2021.08.001DOI Listing
August 2021

Elastic, Dynamic Viscoelastic and Model-Derived Fibril-Reinforced Poroelastic Mechanical Properties of Normal and Osteoarthritic Human Femoral Condyle Cartilage.

Ann Biomed Eng 2021 Aug 2. Epub 2021 Aug 2.

Department of Applied Physics, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland.

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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http://dx.doi.org/10.1007/s10439-021-02838-4DOI Listing
August 2021

An Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss.

Front Bioeng Biotechnol 2021 22;9:680257. Epub 2021 Jun 22.

Department of Movement Sciences, KU Leuven, Leuven, Belgium.

Injurious mechanical loading of articular cartilage and associated lesions compromise the mechanical and structural integrity of joints and contribute to the onset and progression of cartilage degeneration leading to osteoarthritis (OA). Despite extensive and research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration after injury, interact. Recently, techniques provide a unique integrated platform to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration. Here, we introduce a novel integrated Cartilage Adaptive REorientation Degeneration (CARED) algorithm to predict the interaction between degenerative variations in main cartilage constituents, namely collagen fibril disorganization and degradation, proteoglycan (PG) loss, and change in water content. The algorithm iteratively interacts with a finite element (FE) model of a cartilage explant, with and without variable depth to full-thickness defects. In these FE models, intact and injured explants were subjected to normal (2 MPa unconfined compression in 0.1 s) and injurious mechanical loading (4 MPa unconfined compression in 0.1 s). Depending on the mechanical response of the FE model, the collagen fibril orientation and density, PG and water content were iteratively updated. In the CARED model, fixed charge density (FCD) loss and increased water content were related to decrease in PG content. Our model predictions were consistent with earlier experimental studies. In the intact explant model, minimal degenerative changes were observed under normal loading, while the injurious loading caused a reorientation of collagen fibrils toward the direction perpendicular to the surface, intense collagen degradation at the surface, and intense PG loss in the superficial and middle zones. In the injured explant models, normal loading induced intense collagen degradation, collagen reorientation, and PG depletion both on the surface and around the lesion. Our results confirm that the cartilage lesion depth is a crucial parameter affecting tissue degeneration, even under physiological loading conditions. The results suggest that potential fibril reorientation might prevent or slow down fibril degradation under conditions in which the tissue mechanical homeostasis is perturbed like the presence of defects or injurious loading.
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http://dx.doi.org/10.3389/fbioe.2021.680257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258121PMC
June 2021

Biomechanical, biochemical, and near infrared spectral data of bovine knee ligaments and patellar tendon.

Data Brief 2021 Jun 19;36:106976. Epub 2021 Mar 19.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Knee joint ligaments and patellar tendon are rope-like tissues that enable the proper function of the knee by connecting the bones that form the joint. A better understanding of ligament structure-function relationships is needed to develop objective and reliable diagnostic methods for ligaments. Recently, arthroscopic near infrared spectroscopy (NIR) has shown the potential to quantitatively evaluate the health of the cartilages and menisci of the knee. In this dataset, we present a unique combination of NIR spectral data, biomechanical properties, and biochemical composition of bovine primary knee ligaments and patellar tendon (10 knees, 50 tissue samples). NIR spectral data were measured at 5 locations in each sample, biomechanical properties were obtained with tensile testing, and biochemical composition was quantified using colorimetric biochemical methods. The data can be reused for investigations of structure-function relationships of knee ligaments and patellar tendon, for the development of NIR spectroscopic methods to quantify the health of these tissues, and to develop new computational models to describe ligament and tendon biomechanics.
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http://dx.doi.org/10.1016/j.dib.2021.106976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042288PMC
June 2021

Automated analysis of rabbit knee calcified cartilage morphology using micro-computed tomography and deep learning.

J Anat 2021 08 29;239(2):251-263. Epub 2021 Mar 29.

Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.

Structural dynamics of calcified cartilage (CC) are poorly understood. Conventionally, CC structure is analyzed using histological sections. Micro-computed tomography (µCT) allows for three-dimensional (3D) imaging of mineralized tissues; however, the segmentation between bone and mineralized cartilage is challenging. Here, we present state-of-the-art deep learning segmentation for µCT images to assess 3D CC morphology. The sample includes 16 knees from 12 New Zealand White rabbits dissected into osteochondral samples from six anatomical regions: lateral and medial femoral condyles, lateral and medial tibial plateaus, femoral groove, and patella (n = 96). The samples were imaged with µCT and processed for conventional histology. Manually segmented CC from the images was used to train segmentation models with different encoder-decoder architectures. The models with the greatest out-of-fold evaluation Dice score were selected. CC thickness was compared across 24 regions, co-registered between the imaging modalities using Pearson correlation and Bland-Altman analyses. Finally, the anatomical CC thickness variation was assessed via a Linear Mixed Model analysis. The best segmentation models yielded average Dice of 0.891 and 0.807 for histology and µCT segmentation, respectively. The correlation between the co-registered regions was strong (r = 0.897, bias = 21.9 µm, standard deviation = 21.5 µm). Finally, both methods could separate the CC thickness between the patella, femoral, and tibial regions (p < 0.001). As a conclusion, the proposed µCT analysis allows for ex vivo 3D assessment of CC morphology. We demonstrated the biomedical relevance of the method by quantifying CC thickness in different anatomical regions with a varying mean thickness. CC was thickest in the patella and thinnest in the tibial plateau. Our method is relatively straightforward to implement into standard µCT analysis pipelines, allowing the analysis of CC morphology. In future research, µCT imaging might be preferable to histology, especially when analyzing dynamic changes in cartilage mineralization. It could also provide further understanding of 3D morphological changes that may occur in mineralized cartilage, such as thickening of the subchondral plate in osteoarthritis and other joint diseases.
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http://dx.doi.org/10.1111/joa.13435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273618PMC
August 2021

Collagen fibres determine the crack morphology in articular cartilage.

Acta Biomater 2021 05 20;126:301-314. Epub 2021 Mar 20.

Department of Applied Physics, University of Eastern Finland, POB 1627, Kuopio 70211, Finland. Electronic address:

Cracks in articular cartilage compromise tissue integrity and mechanical properties and lead to chondral lesions if untreated. An understanding of the mechanics of cracked cartilage may help in the prevention of cartilage deterioration and the development of tissue-engineered substitutes. The degeneration of cartilage in the presence of cracks may depend on the ultrastructure and composition of the tissue, which changes with aging, disease and habitual loading. It is unknown if the structural and compositional differences between immature and mature cartilage affect the mechanics of cartilage cracks, possibly predisposing one to a greater risk of degeneration than the other. We used a fibre-reinforced poro-viscoelastic swelling material model that accounts for large deformations and tension-compression non-linearity, and the finite element method to investigate the role of cartilage structure and composition on crack morphology and tissue mechanics. We demonstrate that the crack morphology predicted by our theoretical model agrees well with the histo-morphometric images of young and mature cracked cartilages under indentation loading. We also determined that the crack morphology was primarily dependent on collagen fibre orientation which differs as a function of cartilage depth and tissue maturity. The arcade-like collagen fibre orientation, first discussed by Benninghoff in his classical 1925 paper, appears to be beneficial for slowing the progression of tissue cracks by 'sealing' the crack and partially preserving fluid pressure during loading. Preservation of the natural load distribution between solid and fluid constituents of cartilage may be a key factor in slowing or preventing the propagation of tissue cracks and associated tissue matrix damage. STATEMENT OF SIGNIFICANCE: Cracks in articular cartilage can be detrimental to joint health if not treated, but it is not clear how they propagate and lead to tissue degradation. We used an advanced numerical model to determine the role of cartilage structure and composition on crack morphology under loading. Based on the structure and composition found in immature and mature cartilages, our model successfully predicts the crack morphology in these cartilages and determines that collagen fibre as the major determinant of crack morphology. The arcade-like Benninghoff collagen fibre orientation appears to be crucial in 'sealing' the tissue crack and preserves normal fluid-solid load distribution in cartilage. Inclusion of the arcade-like fibre orientation in tissue-engineered construct may help improve its integration within the host tissue.
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http://dx.doi.org/10.1016/j.actbio.2021.03.031DOI Listing
May 2021

Early changes in osteochondral tissues in a rabbit model of post-traumatic osteoarthritis.

J Orthop Res 2021 Feb 13. Epub 2021 Feb 13.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Concurrent osteoarthritic (OA) manifestations in bone and cartilage are poorly known. To shed light on this issue, this study aims to investigate changes in subchondral bone and articular cartilage at two time points after anterior cruciate ligament transection (ACLT) in a rabbit model. 2 (N = 16) and 8 (N = 10) weeks after ACLT, the subchondral bone structure, cartilage thickness, Osteoarthritis Research Society International (OARSI) score, fixed charged density (FCD), and collagen orientation angle were analyzed. OA related changes were evaluated by comparing the ACLT to the contralateral (C-L) and control knees. Already 2 weeks after ACLT, higher trabecular number in the medial femoral condyle and femoral groove, greater OARSI score in the femoral condyles, and thinner trabeculae in the lateral tibial plateau and femoral groove were observed in ACLT compared to C-L knees. Only minor changes of cartilage collagen orientation in the femoral condyles and femoral groove and smaller FCD in the femoral condyles, medial tibial plateau, femoral groove and patella were observed. 8 weeks post-ACLT, the surgical knees had thinner subchondral plate and trabeculae, and smaller trabecular bone volume fraction in most of the knee locations. OARSI score was greater in the femoral condyle and lateral tibial plateau cartilage. FCD loss was progressive only in the femoral condyle, femoral groove, and patellar cartilage, and minor changes of cartilage collagen orientation angle were present in the femoral condyles, femoral groove, and lateral tibial plateau. We conclude that ACLT induces progressive subchondral bone loss, during which proteoglycan loss occurs followed by their partly recovery, as indicated by FCD results.
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http://dx.doi.org/10.1002/jor.25009DOI Listing
February 2021

A numerical framework for mechano-regulated tendon healing-Simulation of early regeneration of the Achilles tendon.

PLoS Comput Biol 2021 02 8;17(2):e1008636. Epub 2021 Feb 8.

Department of Biomedical Engineering, Lund University, Lund, Sweden.

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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http://dx.doi.org/10.1371/journal.pcbi.1008636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901741PMC
February 2021

Structure, composition and fibril-reinforced poroviscoelastic properties of bovine knee ligaments and patellar tendon.

J R Soc Interface 2021 01 27;18(174):20200737. Epub 2021 Jan 27.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Tissue-level stress-relaxation of ligaments and tendons in the toe region is characterized by fast and long-term relaxations and an increase in relaxation magnitude with strain. Characterizing the compositional and structural origins of these phenomena helps in the understanding of mechanisms of ligament and tendon function and adaptation in health and disease. A three-step tensile stress-relaxation test was conducted on dumbbell-shaped pieces of bovine knee ligaments and patellar tendon (PT) ( = 10 knees). Their mechanical behaviour was characterized by a fibril-reinforced poroviscoelastic material model, able to describe characteristic times and magnitudes of fast and long-term relaxations. The crimp angle and length of tissues were measured with polarized light microscopy, while biochemical contents were determined by colorimetric biochemical methods. The long-term relaxation time was longer in the anterior cruciate ligament (ACL) and PT compared with collateral ligaments ( < 0.05). High hydroxyproline content predicted greater magnitude and shorter time of both fast and long-term relaxation. High uronic acid content predicted longer time of long-term relaxation, whereas high crimp angle predicted higher magnitude of long-term relaxation. ACL and PT are better long-term stabilizers than collateral ligaments. The long-term relaxation behaviour is affected or implied by proteoglycans and crimp angle, possibly relating to slow structural reorganization of the tissue.
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http://dx.doi.org/10.1098/rsif.2020.0737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879768PMC
January 2021

Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9-month equine groove model study.

J Orthop Res 2020 Dec 24. Epub 2020 Dec 24.

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.

This study aimed to quantify the long-term progression of blunt and sharp cartilage defects and their effect on joint homeostasis and function of the equine carpus. In nine adult Shetland ponies, the cartilage in the radiocarpal and middle carpal joint of one front limb was grooved (blunt or sharp randomized). The ponies were subjected to an 8-week exercise protocol and euthanized at 39 weeks. Structural and compositional alterations in joint tissues were evaluated in vivo using serial radiographs, synovial biopsies, and synovial fluid samples. Joint function was monitored by quantitative gait analysis. Macroscopic, microscopic, and biomechanical evaluation of the cartilage and assessment of subchondral bone parameters were performed ex vivo. Grooved cartilage showed higher OARSI microscopy scores than the contra-lateral sham-operated controls (p < 0.0001). Blunt-grooved cartilage scored higher than sharp-grooved cartilage (p = 0.007) and fixed charge density around these grooves was lower (p = 0.006). Equilibrium and instantaneous moduli trended lower in grooved cartilage than their controls (significant for radiocarpal joints). Changes in other tissues included a threefold to sevenfold change in interleukin-6 expression in synovium from grooved joints at week 23 (p = 0.042) and an increased CPII/C2C ratio in synovial fluid extracted from blunt-grooved joints at week 35 (p = 0.010). Gait analysis outcome revealed mild, gradually increasing lameness. In conclusion, blunt and, to a lesser extent, sharp grooves in combination with a period of moderate exercise, lead to mild degeneration in equine carpal cartilage over a 9-month period, but the effect on overall joint health remains limited.
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http://dx.doi.org/10.1002/jor.24971DOI Listing
December 2020

Discrete element and finite element methods provide similar estimations for hip joint contact mechanics during walking gait.

J Biomech 2021 01 3;115:110163. Epub 2020 Dec 3.

School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, Australia.

Finite element analysis (FEA) provides a powerful approach for estimating the in-vivo loading characteristics of the hip joint during various locomotory and functional activities. However, time-consuming procedures, such as the generation of high-quality FE meshes and setup of FE simulation, typically make the method impractical for rapid applications which could be used in clinical routine. Alternatively, discrete element analysis (DEA) has been developed to quantify mechanical conditions of the hip joint in a fraction of time compared to FEA. Although DEA has proven effective in the estimation of contact stresses and areas in various complex applications, it has not yet been well characterised by its ability to evaluate contact mechanics for the hip joint during gait cycle loading using data from several individuals. The objective of this work was to compare DEA modelling against well-established FEA for analysing contact mechanics of the hip joint during walking gait. Subject-specific models were generated from magnetic resonance images of the hip joints in five asymptomatic subjects. The DEA and FEA models were then simulated for 13 loading time-points extracted from a full gait cycle. Computationally, DEA was substantially more efficient compared to FEA (simulation times of seconds vs. hours). The DEA and FEA methods had similar predictions for contact pressure distribution for the hip joint during normal walking. In all 13 simulated loading time-points across five subjects, the maximum difference in average contact pressures between DEA and FEA was within ±0.06 MPa. Furthermore, the difference in contact area ratio computed using DEA and FEA was less than ±6%.
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http://dx.doi.org/10.1016/j.jbiomech.2020.110163DOI Listing
January 2021

The effect of body configuration on the strain magnitude and distribution within the acetabulum during sideways falls: A finite element approach.

J Biomech 2021 01 1;114:110156. Epub 2020 Dec 1.

Research Unit of Medical Imaging, Physics, and Technology, University of Oulu, Oulu, Finland; Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland; Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.

While the incidence of hip fractures has declined during the last decades, the incidence of acetabular fractures resulting from low-energy sideways falls has increased, and the mechanisms responsible for this trend remain unknown. Previous studies have suggested that body configuration during the impact plays an important role in a hip fracture. Thus, the aim of this study was to investigate the effect of body configuration angles (trunk tilt angle, trunk flexion angle, femur horizontal rotation angle, and femur diaphysis angle) on low-energy acetabular fractures via a parametric analysis. A computed tomography-based (CT) finite element model of the ground-proximal femur-pelvis complex was created, and strain magnitude, time-history response, and distribution within the acetabulum were evaluated. Results showed that while the trunk tilt angle and femur diaphysis angle have the greatest effect on strain magnitude, the direction of the fall (lateral vs. posterolateral) contributes to strain distribution within the acetabulum. The results also suggest that strain level and distribution within the proximal femur and acetabulum resulting from a sideways fall are not similar and, in some cases, even opposite. Taken together, our simulations suggest that a more horizontal trunk and femoral shaft at the impact phase can increase the risk of low-energy acetabular fractures.
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http://dx.doi.org/10.1016/j.jbiomech.2020.110156DOI Listing
January 2021

Rapid CT-based Estimation of Articular Cartilage Biomechanics in the Knee Joint Without Cartilage Segmentation.

Ann Biomed Eng 2020 Dec 11;48(12):2965-2975. Epub 2020 Nov 11.

Department of Applied Physics, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland.

Knee osteoarthritis (OA) is a painful joint disease, causing disabilities in daily activities. However, there is no known cure for OA, and the best treatment strategy might be prevention. Finite element (FE) modeling has demonstrated potential for evaluating personalized risks for the progression of OA. Current FE modeling approaches use primarily magnetic resonance imaging (MRI) to construct personalized knee joint models. However, MRI is expensive and has lower resolution than computed tomography (CT). In this study, we extend a previously presented atlas-based FE modeling framework for automatic model generation and simulation of knee joint tissue responses using contrast agent-free CT. In this method, based on certain anatomical dimensions measured from bone surfaces, an optimal template is selected and scaled to generate a personalized FE model. We compared the simulated tissue responses of the CT-based models with those of the MRI-based models. We show that the CT-based models are capable of producing similar tensile stresses, fibril strains, and fluid pressures of knee joint cartilage compared to those of the MRI-based models. This study provides a new methodology for the analysis of knee joint and cartilage mechanics based on measurement of bone dimensions from native CT scans.
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http://dx.doi.org/10.1007/s10439-020-02666-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723937PMC
December 2020

Structure-Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation.

Ann Biomed Eng 2020 Dec 9;48(12):2887-2900. Epub 2020 Jul 9.

Department of Applied Physics, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland.

Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n = 27). At a low frequency (0.005 Hz), proteoglycan content correlated negatively and collagen content correlated positively with the phase difference (i.e. tissue viscosity). At a high-frequency regime (> 0.05 Hz), proteoglycan content correlated negatively and collagen orientation angle correlated positively with the phase difference. Proteoglycans were lost in the early and advanced OA groups compared to the healthy group, while the superficial collagen orientation angle was greater only in the advanced OA group compared to the healthy group. Simultaneously, the initial fibril network modulus (fibril pretension) was smaller in the early and advanced OA groups compared to the healthy group. These findings suggest different mechanisms contribute to cartilage viscosity in low and high frequencies, and that the loss of superficial collagen pretension during early OA is due to lower tissue swelling (PG loss), while in advanced OA, both collagen disorganization and lower swelling modulate the collagen fibril pretension.
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http://dx.doi.org/10.1007/s10439-020-02559-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723942PMC
December 2020

Prediction of local fixed charge density loss in cartilage following ACL injury and reconstruction: A computational proof-of-concept study with MRI follow-up.

J Orthop Res 2021 05 20;39(5):1064-1081. Epub 2020 Jul 20.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

The purpose of this proof-of-concept study was to develop three-dimensional patient-specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imaging (MRI) data were used for segmenting the knee geometries, including the cartilage lesions. Based on these geometries, finite element (FE) models were developed. The gait of the patients was obtained using a motion capture system. Musculoskeletal modeling was utilized to calculate knee joint contact and lower extremity muscle forces for the FE models. Finally, a cartilage adaptation algorithm was implemented in both FE models. In the algorithm, it was assumed that excessive maximum shear and deviatoric strains (calculated as the combination of principal strains), and fluid velocity, are responsible for the FCD loss. Changes in the longitudinal T and T relaxation times were postulated to be related to changes in the cartilage composition and were compared with the numerical predictions. In patient 1 model, both the excessive fluid velocity and strain caused the FCD loss primarily near the cartilage lesion. T and T relaxation times increased during the follow-up in the same location. In contrast, in patient 2 model, only the excessive fluid velocity led to a slight FCD loss near the lesion, where MRI parameters did not show evidence of alterations. Significance: This novel proof-of-concept study suggests mechanisms through which a local FCD loss might occur near cartilage lesions. In order to obtain statistical evidence for these findings, the method should be investigated with a larger cohort of subjects.
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http://dx.doi.org/10.1002/jor.24797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790898PMC
May 2021

Mechanobiological model for simulation of injured cartilage degradation via pro-inflammatory cytokines and mechanical stimulus.

PLoS Comput Biol 2020 06 25;16(6):e1007998. Epub 2020 Jun 25.

Department of Applied Physics, University of Eastern Finland, Finland.

Post-traumatic osteoarthritis (PTOA) is associated with cartilage degradation, ultimately leading to disability and decrease of quality of life. Two key mechanisms have been suggested to occur in PTOA: tissue inflammation and abnormal biomechanical loading. Both mechanisms have been suggested to result in loss of cartilage proteoglycans, the source of tissue fixed charge density (FCD). In order to predict the simultaneous effect of these degrading mechanisms on FCD content, a computational model has been developed. We simulated spatial and temporal changes of FCD content in injured cartilage using a novel finite element model that incorporates (1) diffusion of the pro-inflammatory cytokine interleukin-1 into tissue, and (2) the effect of excessive levels of shear strain near chondral defects during physiologically relevant loading. Cytokine-induced biochemical cartilage explant degradation occurs near the sides, top, and lesion, consistent with the literature. In turn, biomechanically-driven FCD loss is predicted near the lesion, in accordance with experimental findings: regions near lesions showed significantly more FCD depletion compared to regions away from lesions (p<0.01). Combined biochemical and biomechanical degradation is found near the free surfaces and especially near the lesion, and the corresponding bulk FCD loss agrees with experiments. We suggest that the presence of lesions plays a role in cytokine diffusion-driven degradation, and also predisposes cartilage for further biomechanical degradation. Models considering both these cartilage degradation pathways concomitantly are promising in silico tools for predicting disease progression, recognizing lesions at high risk, simulating treatments, and ultimately optimizing treatments to postpone the development of PTOA.
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http://dx.doi.org/10.1371/journal.pcbi.1007998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343184PMC
June 2020

Machine Learning Classification of Articular Cartilage Integrity Using Near Infrared Spectroscopy.

Cell Mol Bioeng 2020 Jun 9;13(3):219-228. Epub 2020 Mar 9.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Introduction: Assessment of cartilage integrity during arthroscopy is limited by the subjective visual nature of the technique. To address this shortcoming in diagnostic evaluation of articular cartilage, near infrared spectroscopy (NIRS) has been proposed. In this study, we evaluated the capacity of NIRS, combined with machine learning techniques, to classify cartilage integrity.

Methods: Rabbit ( = 14) knee joints with artificial injury, induced unilateral anterior cruciate ligament transection (ACLT), and the corresponding contra-lateral (CL) joints, including joints from separate non-operated control (CNTRL) animals ( = 8), were used. After sacrifice, NIR spectra (1000-2500 nm) were acquired from different anatomical locations of the joints (  = 313:  = 111,  = 97,  = 105). Machine and deep learning methods (support vector machines-SVM, logistic regression-LR, and deep neural networks-DNN) were then used to develop models for classifying the samples based solely on their NIR spectra.

Results: The results show that the model based on SVM is optimal of distinguishing between ACLT and CNTRL samples (ROC_AUC = 0.93, kappa = 0.86), LR is capable of distinguishing between CL and CNTRL samples (ROC_AUC = 0.91, kappa = 0.81), while DNN is optimal for discriminating between the different classes (multi-class classification, kappa = 0.48).

Conclusion: We show that NIR spectroscopy, when combined with machine learning techniques, is capable of holistic assessment of cartilage integrity, with potential for accurately distinguishing between healthy and diseased cartilage.
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http://dx.doi.org/10.1007/s12195-020-00612-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225230PMC
June 2020

Multiparametric MR imaging reveals early cartilage degeneration at 2 and 8 weeks after ACL transection in a rabbit model.

J Orthop Res 2020 09 10;38(9):1974-1986. Epub 2020 Mar 10.

Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.

In this study, the rabbit model with anterior cruciate ligament transection (ACLT) was used to investigate early degenerative changes in cartilage using multiparametric quantitative magnetic resonance imaging (qMRI). ACLT was surgically induced in the knees of skeletally mature New Zealand White rabbits (n = 14). ACL transected and contralateral knee compartments-medial femur, lateral femur, medial tibia, and lateral tibia-were harvested 2 (n = 8) and 8 weeks (n = 6) postsurgery. Twelve age-matched nonoperated rabbits served as control. qMRI was conducted at 9.4 T and included relaxation times T , T , continuous-wave T (CWT ), adiabatic T (AdT ), adiabatic T (AdT ), and relaxation along a fictitious field (T ). For reference, quantitative histology and biomechanical measurements were carried out. Posttraumatic changes were primarily noted in the superficial half of the cartilage. Prolonged T , T , CWT , and AdT were observed in the lateral femur 2 and 8 weeks post-ACLT, compared with the corresponding control and contralateral groups (P < .05). Collagen orientation was significantly altered in the lateral femur at 2 weeks post-ACLT compared with the corresponding control group. In the medial femur, all the studied relaxation time parameters, except T , were increased 8 weeks post-ACLT, as compared with the corresponding contralateral and control groups (P < .05). Similarly, significant proteoglycan loss was observed in the medial femur at 8 weeks following surgery (P < .05). Multiparametric MRI demonstrated early degenerative changes primarily in the superficial cartilage with T , T , CWT , and AdT sensitive to cartilage changes at 2 weeks after surgery.
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http://dx.doi.org/10.1002/jor.24644DOI Listing
September 2020

Raman microspectroscopic analysis of the tissue-specific composition of the human osteochondral junction in osteoarthritis: A pilot study.

Acta Biomater 2020 04 17;106:145-155. Epub 2020 Feb 17.

Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.

This study investigates the influence of osteoarthritis (OA) disease severity on the bio-composition of the osteochondral junction at the human tibial plateau using Raman microspectroscopy. We specifically aim to analyze the spatial composition of mineralized osteochondral tissues, i.e., calcified cartilage (CC) and subchondral bone plate (SBP) from unfixed, hydrated specimens. We hypothesize that the mineralization of CC and SBP decreases in advanced OA. Twenty-eight cylindrical osteochondral samples (d = 4 mm) from tibial plateaus of seven cadaveric donors were harvested and sorted into three groups following histopathological grading: healthy (n = 5), early OA (n = 8), and advanced OA (n = 15). Raman spectra were subjected to multivariate cluster analyses to identify different tissues. Finally, the tissue-specific composition was analyzed, and the impact of OA was statistically evaluated with linear mixed models. Cluster analyses of Raman spectra successfully distinguished CC and SBP as well as a tidemark region and uncalcified cartilage. CC was found to be more mineralized and the mineral was more crystalline compared with SBP. Both tissues exhibited similar compositional changes as a function of histopathological OA severity. In early OA, the mineralization tends to increase, and the mineral contains fewer carbonate substitutions. Compared with early OA, mineral crystals are rich in carbonate while the overall mineralization decreases in advanced OA. This Raman spectroscopic study advances the methodology for investigating the complex osteochondral junction from native tissue. The developed methodology can be used to elucidate detailed tissue-specific changes in the chemical composition with advancing OA. STATEMENT OF SIGNIFICANCE: In this study, Raman microspectroscopy was utilized to investigate the influence of osteoarthritic degeneration on the tissue-specific biochemical composition of the human osteochondral junction. Multivariate cluster analyses allowed us to characterize subtle compositional changes in the calcified cartilage and subchondral bone plate as well as in the tidemark region. The compositional differences found between the calcified cartilage and subchondral bone plate in both organic and mineral phases will serve as critical benchmark parameters when designing biomaterials for osteochondral repair. We found tissue-specific changes in the mineralization and carbonate substitution as a function of histopathological OA severity. Our developed methodology can be used to investigate the metabolic changes in the osteochondral junction associated with osteoarthritis.
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http://dx.doi.org/10.1016/j.actbio.2020.02.020DOI Listing
April 2020

A multiscale framework for evaluating three-dimensional cell mechanics in fibril-reinforced poroelastic tissues with anatomical cell distribution - Analysis of chondrocyte deformation behavior in mechanically loaded articular cartilage.

J Biomech 2020 03 17;101:109648. Epub 2020 Jan 17.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Characterization of the mechanical environment of cells in collagenous biological tissues during different daily activities is crucial for understanding the role of mechanics on cell biosynthesis and tissue health. However, current imaging methods are limited in characterizing very fast deformations of cells. This could be achieved with computational multiscale modeling, but current models accommodating collagen fibril networks and poroelastic ground matrix have included only a single cell. In this study, a workflow was developed for generating a three-dimensional multiscale model with imaging-based anatomical cell distributions and their micro-environment (pericellular and extracellular matrix). Fibril-reinforced poroelastic material models with (FRPES) and without (FRPE) swelling were implemented into the model and simulations were performed for evaluating cell deformations before and after experimental loading conducted for rabbit knee joint cartilage. We observed that the cells experienced considerably different deformation based on their location in all models. Both FRPE and FRPES models were able to predict the trends in the changes in cell deformations, although the average and median magnitudes differed between the model predictions and experiments. However, the FRPES model results were generally closer to the experimental results. Current findings suggest that morphological properties of cells are affected by the variations in the tissue properties between the samples and variations within the sample caused by the measurement geometry, local structure and composition. Thus, it would be important to consider the anatomical distribution and location of multiple cells along with the structure of fibril networks if cell deformation metrics are evaluated in collagenous tissues.
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http://dx.doi.org/10.1016/j.jbiomech.2020.109648DOI Listing
March 2020

Anterior cruciate ligament transection of rabbits alters composition, structure and biomechanics of articular cartilage and chondrocyte deformation 2 weeks post-surgery in a site-specific manner.

J Biomech 2020 01 23;98:109450. Epub 2019 Oct 23.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland. Electronic address:

Anterior cruciate ligament (ACL) injury often leads to post-traumatic osteoarthritis (OA) and articular cartilage degradation, changing biomechanics of the tissue and chondrocytes, and altering the fixed charged density (FCD) and collagen network. However, changes in these properties are not known at a very early time point after ACL rupture, but recognizing early changes might be crucial for successful intervention. We investigated the effects of ACL transection (ACLT) in rabbits on the site-specific biomechanical properties of articular cartilage and chondrocytes, FCD content and collagen network organization, two weeks post-surgery. Unilateral ACLT was performed in eight rabbits, and femoral condyles, tibial plateaus, femoral grooves and patellae were harvested from experimental and contralateral knee joints. An intact control group was used as a reference. We analyzed chondrocyte morphology under pre- and static loading, cartilage biomechanical properties, FCD content and collagen fibril orientation. ACLT caused FCD loss in the lateral and medial femoral condyle, lateral tibial plateau, femoral groove and patellar cartilage (p < 0.05). Minor changes in the collagen orientation occurred in the femoral groove and lateral and medial femoral condyle cartilage (p < 0.05). Cartilage stiffness was reduced in the lateral and medial femoral condyles, and chondrocyte biomechanics was altered in the lateral femoral condyle and patellar cartilage (p < 0.05). We observed loss of FCD from articular cartilage two weeks after ACLT at several joint locations. These changes may have led to decreased cartilage stiffness and altered cell deformation behavior, especially in the femoral condyles.
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http://dx.doi.org/10.1016/j.jbiomech.2019.109450DOI Listing
January 2020

Clinical Contrast-Enhanced Computed Tomography With Semi-Automatic Segmentation Provides Feasible Input for Computational Models of the Knee Joint.

J Biomech Eng 2020 05;142(5)

Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland.

Computational models can provide information on joint function and risk of tissue failure related to progression of osteoarthritis (OA). Currently, the joint geometries utilized in modeling are primarily obtained via manual segmentation, which is time-consuming and hence impractical for direct clinical application. The aim of this study was to evaluate the applicability of a previously developed semi-automatic method for segmenting tibial and femoral cartilage to serve as input geometry for finite element (FE) models. Knee joints from seven volunteers were first imaged using a clinical computed tomography (CT) with contrast enhancement and then segmented with semi-automatic and manual methods. In both segmentations, knee joint models with fibril-reinforced poroviscoelastic (FRPVE) properties were generated and the mechanical responses of articular cartilage were computed during physiologically relevant loading. The mean differences in the absolute values of maximum principal stress, maximum principal strain, and fibril strain between the models generated from semi-automatic and manual segmentations were <1 MPa, <0.72% and <0.40%, respectively. Furthermore, contact areas, contact forces, average pore pressures, and average maximum principal strains were not statistically different between the models (p >0.05). This semi-automatic method speeded up the segmentation process by over 90% and there were only negligible differences in the results provided by the models utilizing either manual or semi-automatic segmentations. Thus, the presented CT imaging-based segmentation method represents a novel tool for application in FE modeling in the clinic when a physician needs to evaluate knee joint function.
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http://dx.doi.org/10.1115/1.4045279DOI Listing
May 2020

Identification of locations susceptible to osteoarthritis in patients with anterior cruciate ligament reconstruction: Combining knee joint computational modelling with follow-up T and T imaging.

Clin Biomech (Bristol, Avon) 2020 10 9;79:104844. Epub 2019 Aug 9.

Department of Applied Physics, University of Eastern Finland, POB 1627, FI-70211 Kuopio, Finland; Diagnostic Imaging Centre, Kuopio University Hospital, POB 100, FI-70029 KUH Kuopio, Finland. Electronic address:

Background: Finite element modelling can be used to evaluate altered loading conditions and failure locations in knee joint tissues. One limitation of this modelling approach has been experimental comparison. The aims of this proof-of-concept study were: 1) identify areas susceptible to osteoarthritis progression in anterior cruciate ligament reconstructed patients using finite element modelling; 2) compare the identified areas against changes in T and T values between 1-year and 3-year follow-up timepoints.

Methods: Two patient-specific finite element models of knee joints with anterior cruciate ligament reconstruction were created. The knee geometry was based on clinical magnetic resonance imaging and joint loading was obtained via motion capture. We evaluated biomechanical parameters linked with cartilage degeneration and compared the identified risk areas against T and T maps.

Findings: The risk areas identified by the finite element models matched the follow-up magnetic resonance imaging findings. For Patient 1, excessive values of maximum principal stresses and shear strains were observed in the posterior side of the lateral tibial and femoral cartilage. For Patient 2, high values of maximum principal stresses and shear strains of cartilage were observed in the posterior side of the medial joint compartment. For both patients, increased T and T values between the follow-up times were observed in the same areas.

Interpretation: Finite element models with patient-specific geometries and motions and relatively simple material models of tissues were able to identify areas susceptible to post-traumatic knee osteoarthritis. We suggest that the methodology presented here may be applied in large cohort studies.
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http://dx.doi.org/10.1016/j.clinbiomech.2019.08.004DOI Listing
October 2020

Eight-year trajectories of changes in health-related quality of life in knee osteoarthritis: Data from the Osteoarthritis Initiative (OAI).

PLoS One 2019 19;14(7):e0219902. Epub 2019 Jul 19.

Pharmacoeconomics and Outcomes Research Unit, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

Background: Knee osteoarthritis (OA) worsens health-related quality of life (HRQoL) but the symptom pathway varies from person to person. We aimed to identify groups of people with knee OA or at its increased risk whose HRQoL changed similarly. Our secondary aim was to evaluate if patient-related characteristics, incidence of knee replacement (KR) and prevalence of pain medication use differed between the identified HRQoL trajectory groups.

Methods: Eight-year follow-up data of 3053 persons with mild knee OA or at increased risk were obtained from the public Osteoarthritis Initiative (OAI) database. Group-based trajectory modeling was used to identify patterns of experiencing a decrease of ≥10 points (Minimal Important Change, MIC) in the Quality of Life subscale of the Knee injury and Osteoarthritis Outcome Score compared to baseline. Multinomial logistic regression, Cox regression and generalized estimating equation models were used to study secondary aims.

Results: Four HRQoL trajectory groups were identified. Persons in the 'no change' group (62.9%) experienced no worsening in HRQoL. 'Rapidly' (9.5%) and 'slowly' worsening (17.1%) groups displayed an increasing probability of experiencing the MIC in HRQoL. The fourth group (10.4%) had 'improving' HRQoL. Female gender, higher body mass index, smoking, knee pain, and lower income at baseline were associated with belonging to the 'rapidly worsening' group. People in 'rapidly' (hazard ratio (HR) 6.2, 95% confidence interval (CI) 3.6-10.7) and 'slowly' worsening (HR 3.4, 95% CI 2.0-5.9) groups had an increased risk of requiring knee replacement. Pain medication was more rarely used in the 'no change' than in the other groups.

Conclusions: HRQoL worsening was associated with several risk factors; surgical and pharmacological interventions were more common in the poorer HRQoL trajectory groups indicating that HRQoL does reflect the need for OA treatment. These findings may have implications for targeting interventions to specific knee OA patient groups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219902PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641160PMC
March 2020

Publisher Correction: Quantitative Evaluation of the Mechanical Risks Caused by Focal Cartilage Defects in the Knee.

Sci Rep 2019 Apr 4;9(1):5660. Epub 2019 Apr 4.

Department of Applied Physics, University of Eastern Finland, POB 1627, FI-70211, Kuopio, Finland.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-019-41384-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449340PMC
April 2019

Anterior cruciate ligament transection alters the n-3/n-6 fatty acid balance in the lapine infrapatellar fat pad.

Lipids Health Dis 2019 Mar 18;18(1):67. Epub 2019 Mar 18.

Institute of Biomedicine/Anatomy, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.

Background: The infrapatellar fat pad (IFP) of the knee joint has received lots of attention recently due to its emerging role in the pathogenesis of osteoarthritis (OA), where it displays an inflammatory phenotype. The aim of the present study was to examine the infrapatellar fatty acid (FA) composition in a rabbit (Oryctolagus cuniculus) model of early OA created by anterior cruciate ligament transection (ACLT).

Methods: OA was induced randomly in the left or right knee joint of skeletally mature New Zealand White rabbits by ACLT, while the contralateral knee was left intact. A separate group of unoperated rabbits served as controls. The IFP of the ACLT, contralateral, and control knees were harvested following euthanasia 2 or 8 weeks post-ACLT and their FA composition was determined with gas chromatography-mass spectrometry.

Results: The n-3/n-6 polyunsaturated FA (PUFA) ratio shifted in a pro-inflammatory direction after ACLT, already observed 2 weeks after the operation (0.20 ± 0.008 vs. 0.18 ± 0.009). At 8 weeks, the FA profile of the ACLT group was characterized with increased percentages of 20:4n-6 (0.44 ± 0.064 vs. 0.98 ± 0.339 mol-%) and 22:6n-3 (0.03 ± 0.014 vs. 0.07 ± 0.015 mol-%) and with decreased monounsaturated FA (MUFA) sums (37.19 ± 1.586 vs. 33.20 ± 1.068 mol-%) and n-3/n-6 PUFA ratios (0.20 ± 0.008 vs. 0.17 ± 0.008). The FA signature of the contralateral knees resembled that of the unoperated controls in most aspects, but had increased proportions of total n-3 PUFA and reduced MUFA sums.

Conclusions: These findings provide novel information on the effects of early OA on the infrapatellar FA profile in the rabbit ACLT model. The reduction in the n-3/n-6 PUFA ratio of the IFP is in concordance with the inflammation and cartilage degradation in early OA and could contribute to disease pathogenesis.
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http://dx.doi.org/10.1186/s12944-019-1008-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421636PMC
March 2019

Experimental mechanical strain measurement of tissues.

PeerJ 2019 7;7:e6545. Epub 2019 Mar 7.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Strain, an important biomechanical factor, occurs at different scales from molecules and cells to tissues and organs in physiological conditions. Under mechanical strain, the strength of tissues and their micro- and nanocomponents, the structure, proliferation, differentiation and apoptosis of cells and even the cytokines expressed by cells probably shift. Thus, the measurement of mechanical strain (i.e., relative displacement or deformation) is critical to understand functional changes in tissues, and to elucidate basic relationships between mechanical loading and tissue response. In the last decades, a great number of methods have been developed and applied to measure the deformations and mechanical strains in tissues comprising bone, tendon, ligament, muscle and brain as well as blood vessels. In this article, we have reviewed the mechanical strain measurement from six aspects: electro-based, light-based, ultrasound-based, magnetic resonance-based and computed tomography-based techniques, and the texture correlation-based image processing method. The review may help solving the problems of experimental and mechanical strain measurement of tissues under different measurement environments.
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http://dx.doi.org/10.7717/peerj.6545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409087PMC
March 2019

Computational evaluation of altered biomechanics related to articular cartilage lesions observed in vivo.

J Orthop Res 2019 05 28;37(5):1042-1051. Epub 2019 Mar 28.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Chondral lesions provide a potential risk factor for development of osteoarthritis. Despite the variety of in vitro studies on lesion degeneration, in vivo studies that evaluate relation between lesion characteristics and the risk for the possible progression of OA are lacking. Here, we aimed to characterize different lesions and quantify biomechanical responses experienced by surrounding cartilage tissue. We generated computational knee joint models with nine chondral injuries based on clinical in vivo arthrographic computed tomography images. Finite element models with fibril-reinforced poro(visco)elastic cartilage and menisci were constructed to simulate physiological loading. Systematically, the lesions experienced increased peak values of maximum principal strain, maximum shear strain, and minimum principal strain in the surrounding chondral tissue (p < 0.01) compared with intact tissue. Depth, volume, and area of the lesion correlated with the maximum shear strain (p < 0.05, Spearman rank correlation coefficient ρ = 0.733-0.917). Depth and volume of the lesion correlated also with the maximum principal strain (p < 0.05, ρ = 0.767, and ρ = 0.717, respectively). However, the lesion area had non-significant correlation with this strain parameter (p = 0.06, ρ = 0.65). Potentially, the introduced approach could be developed for clinical evaluation of biomechanical risks of a chondral lesion and planning an intervention. Statement of Clinical Relevance: In this study, we computationally characterized different in vivo chondral lesions and evaluated their risk of cartilage degeneration. This information is vital in decision-making for intervention in order to prevent post-traumatic osteoarthritis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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http://dx.doi.org/10.1002/jor.24273DOI Listing
May 2019
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