Cell deformation behavior in mechanically loaded rabbit articular cartilage 4 weeks after anterior cruciate ligament transection

SummaryObjectiveChondrocyte stresses and strains in articular cartilage are known to modulate tissue mechanobiology. Cell deformation behavior in cartilage under mechanical loading is not known at the earliest stages of osteoarthritis. Thus, the aim of this study was to investigate the effect of mechanical loading on volume and morphology of chondrocytes in the superficial tissue of osteoarthritic cartilage obtained from anterior cruciate ligament transected (ACLT) rabbit knee joints, 4 weeks after intervention.MethodsA unique custom-made microscopy indentation system with dual-photon microscope was used to apply controlled 2 MPa force-relaxation loading on patellar cartilage surfaces. Volume and morphology of chondrocytes were analyzed before and after loading. Also global and local tissue strains were calculated. Collagen content, collagen orientation and proteoglycan content were quantified with Fourier transform infrared microspectroscopy, polarized light microscopy and digital densitometry, respectively.ResultsFollowing the mechanical loading, the volume of chondrocytes in the superficial tissue increased significantly in ACLT cartilage by 24% (95% confidence interval (CI) 17.2–31.5, P < 0.001), while it reduced significantly in contralateral group tissue by −5.3% (95% CI −8.1 to −2.5, P = 0.003). Collagen content in ACLT and contralateral cartilage were similar. PG content was reduced and collagen orientation angle was increased in the superficial tissue of ACLT cartilage compared to the contralateral cartilage.ConclusionsWe found the novel result that chondrocyte deformation behavior in the superficial tissue of rabbit articular cartilage is altered already at 4 weeks after ACLT, likely because of changes in collagen fibril orientation and a reduction in PG content

Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics

SummaryObjectiveOsteoarthritis (OA) is characterized by the changes in structure and composition of articular cartilage. However, it is not fully known, what is the depth-wise change in two major components of the cartilage solid matrix, i.e., collagen and proteoglycans (PGs), during OA progression. Further, it is unknown how the depth-wise changes affect local tissue strains during compression. Our aim was to address these issues.MethodsData from the previous microscopic and biochemical measurements of the collagen content, distribution and orientation, PG content and distribution, water content and histological grade of normal and degenerated human patellar articular cartilage (n=73) were reanalyzed in a depth-wise manner. Using this information, a composition-based finite element (FE) model was used to estimate tissue function solely based on its composition and structure.ResultsThe orientation angle of collagen fibrils in the superficial zone of cartilage was significantly less parallel to the surface (P<0.05) in samples with early degeneration than in healthy samples. Similarly, PG content was reduced in the superficial zone in early OA (P<0.05). However, collagen content decreased significantly only at the advanced stage of OA (P<0.05). The composition-based FE model showed that under a constant stress, local tissue strains increased as OA progressed.ConclusionFor the first time, depth-wise point-by-point statistical comparisons of structure and composition of human articular cartilage were conducted. The present results indicated that early OA is primarily characterized by the changes in collagen orientation and PG content in the superficial zone, while collagen content does not change until OA has progressed to its late stage. Our simulation results suggest that impact loads in OA joint could create a risk for tissue failure and cell death

Iterative and discrete reconstruction in the evaluation of the rabbit model of osteoarthritis

Micro-computed tomography (µCT) is a standard method for bone morphometric evaluation. However, the scan time can be long and the radiation dose during the scan may have adverse effects on test subjects, therefore both of them should be minimized. This could be achieved by applying iterative reconstruction (IR) on sparse projection data, as IR is capable of producing reconstructions of sufficient image quality with less projection data than the traditional algorithm requires. In this work, the performance of three IR algorithms was assessed for quantitative bone imaging from low-resolution data in the evaluation of the rabbit model of osteoarthritis. Subchondral bone images were reconstructed with a conjugate gradient least squares algorithm, a total variation regularization scheme, and a discrete algebraic reconstruction technique to obtain quantitative bone morphometry, and the results obtained in this manner were compared with those obtained from the reference reconstruction. Our approaches were sufficient to identify changes in bone structure in early osteoarthritis, and these changes were preserved even when minimal data were provided for the reconstruction. Thus, our results suggest that IR algorithms give reliable performance with sparse projection data, thereby recommending them for use in µCT studies where time and radiation exposure are preferably minimized. © 2018, The Author(s).Peer reviewe

Estimation of articular cartilage properties using multivariate analysis of optical coherence tomography signal

SummaryObjectiveThe aim was to investigate the applicability of multivariate analysis of optical coherence tomography (OCT) information for determining structural integrity, composition and mechanical properties of articular cartilage.DesignEquine osteochondral samples (N = 65) were imaged with OCT, and their total attenuation and backscattering coefficients (μt and μb) were measured. Subsequently, the Mankin score, optical density (OD) describing the fixed charge density, light absorbance in amide I region (Aamide), collagen orientation, permeability, fibril network modulus (Ef) and non-fibrillar matrix modulus (Em) of the samples were determined. Partial least squares (PLS) regression model was calculated to predict tissue properties from the OCT signals of the samples.ResultsSignificant correlations between the measured and predicted mean collagen orientation (R2 = 0.75, P < 0.0001), permeability (R2 = 0.74, P < 0.0001), mean OD (R2 = 0.73, P < 0.0001), Mankin scores (R2 = 0.70, P < 0.0001), Em (R2 = 0.50, P < 0.0001), Ef (R2 = 0.42, P < 0.0001), and Aamide (R2 = 0.43, P < 0.0001) were obtained. Significant correlation was also found between μb and Ef (ρ = 0.280, P = 0.03), but not between μt and any of the determined properties of articular cartilage (P > 0.05).ConclusionMultivariate analysis of OCT signal provided good estimates for tissue structure, composition and mechanical properties. This technique may significantly enhance OCT evaluation of articular cartilage integrity, and could be applied, for example, in delineation of degenerated areas around cartilage injuries during arthroscopic repair surgery

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

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

Development of a planar multi-body model of the human knee joint

The aim of this work is to develop a dynamic model for the biological human knee joint. The model is formulated in the framework of multibody systems methodologies, as a system of two bodies, the femur and the tibia. For the purpose of describing the formulation, the relative motion of the tibia with respect to the femur is considered. Due to their higher stiffness compared to that of the articular cartilages, the femur and tibia are considered as rigid bodies. The femur and tibia cartilages are considered to be deformable structures with specific material characteristics. The rotation and gliding motions of the tibia relative to the femur can not be modeled with any conventional kinematic joint, but rather in terms of the action of the knee ligaments and potential contact between the bones. Based on medical imaging techniques, the femur and tibia profiles in the sagittal plane are extracted and used to define the interface geometric conditions for contact. When a contact is detected, a continuous non-linear contact force law is applied which calculates the contact forces developed at the interface as a function of the relative indentation between the two bodies. The four basic cruciate and collateral ligaments present in the knee are also taken into account in the proposed knee joint model, which are modeled as non-linear elastic springs. The forces produced in the ligaments, together with the contact forces, are introduced into the system’s equations of motion as external forces. In addition, an external force is applied on the center of mass of the tibia, in order to actuate the system mimicking a normal gait motion. Finally, numerical results obtained from computational simulations are used to address the assumptions and procedures adopted in this study.Fundação para a Ciência e a Tecnologia (FCT

Campaign 9 of the K2 Mission: Observational Parameters, Scientific Drivers, and Community Involvement for a Simultaneous Space- and Ground-based Microlensing Survey

K2's Campaign 9 (K2C9) will conduct a ~3.7 deg2 survey toward the Galactic bulge from 2016 April 22 through July 2 that will leverage the spatial separation between K2 and the Earth to facilitate measurement of the microlens parallax ${\pi }_{{\rm{E}}}$ for $\gtrsim 170$ microlensing events. These will include several that are planetary in nature as well as many short-timescale microlensing events, which are potentially indicative of free-floating planets (FFPs). These satellite parallax measurements will in turn allow for the direct measurement of the masses of and distances to the lensing systems. In this article we provide an overview of the K2C9 space- and ground-based microlensing survey. Specifically, we detail the demographic questions that can be addressed by this program, including the frequency of FFPs and the Galactic distribution of exoplanets, the observational parameters of K2C9, and the array of resources dedicated to concurrent observations. Finally, we outline the avenues through which the larger community can become involved, and generally encourage participation in K2C9, which constitutes an important pathfinding mission and community exercise in anticipation of WFIRST

Importance of collagen orientation and depth-dependent fixed charge densities of cartilage on mechanical behavior of chondrocytes.

The collagen network and proteoglycan matrix of articular cartilage are thought to play an important role in controlling the stresses and strains in and around chondrocytes, in regulating the biosynthesis of the solid matrix, and consequently in maintaining the health of diarthrodial joints. Understanding the detailed effects of the mechanical environment of chondrocytes on cell behavior is therefore essential for the study of the development, adaptation, and degeneration of articular cartilage. Recent progress in macroscopic models has improved our understanding of depth-dependent properties of cartilage. However, none of the previous works considered the effect of realistic collagen orientation or depth-dependent negative charges in microscopic models of chondrocyte mechanics. The aim of this study was to investigate the effects of the collagen network and fixed charge densities of cartilage on the mechanical environment of the chondrocytes in a depth-dependent manner. We developed an anisotropic, inhomogeneous, microstructural fibril-reinforced finite element model of articular cartilage for application in unconfined compression. The model consisted of the extracellular matrix and chondrocytes located in the superficial, middle, and deep zones. Chondrocytes were surrounded by a pericellular matrix and were assumed spherical prior to tissue swelling and load application. Material properties of the chondrocytes, pericellular matrix, and extracellular matrix were obtained from the literature. The loading protocol included a free swelling step followed by a stress-relaxation step. Results from traditional isotropic and transversely isotropic biphasic models were used for comparison with predictions from the current model. In the superficial zone, cell shapes changed from rounded to elliptic after free swelling. The stresses and strains as well as fluid flow in cells were greatly affected by the modulus of the collagen network. The fixed charge density of the chondrocytes, pericellular matrix, and extracellular matrix primarily affected the aspect ratios (height/ width) and the solid matrix stresses of cells. The mechanical responses of the cells were strongly location and time dependent. The current model highlights that the collagen orientation and the depth-dependent negative fixed charge densities of articular cartilage have a great effect in modulating the mechanical environment in the vicinity of chondrocytes, and it provides an important improvement over earlier models in describing the possible pathways from loading of articular cartilage to the mechanical and biological responses of chondrocytes

Importance of collagen orientation and depth-dependent fixed charge densities of cartilage on mechanical behavior of chondrocytes.

The collagen network and proteoglycan matrix of articular cartilage are thought to play an important role in controlling the stresses and strains in and around chondrocytes, in regulating the biosynthesis of the solid matrix, and consequently in maintaining the health of diarthrodial joints. Understanding the detailed effects of the mechanical environment of chondrocytes on cell behavior is therefore essential for the study of the development, adaptation, and degeneration of articular cartilage. Recent progress in macroscopic models has improved our understanding of depth-dependent properties of cartilage. However, none of the previous works considered the effect of realistic collagen orientation or depth-dependent negative charges in microscopic models of chondrocyte mechanics. The aim of this study was to investigate the effects of the collagen network and fixed charge densities of cartilage on the mechanical environment of the chondrocytes in a depth-dependent manner. We developed an anisotropic, inhomogeneous, microstructural fibril-reinforced finite element model of articular cartilage for application in unconfined compression. The model consisted of the extracellular matrix and chondrocytes located in the superficial, middle, and deep zones. Chondrocytes were surrounded by a pericellular matrix and were assumed spherical prior to tissue swelling and load application. Material properties of the chondrocytes, pericellular matrix, and extracellular matrix were obtained from the literature. The loading protocol included a free swelling step followed by a stress-relaxation step. Results from traditional isotropic and transversely isotropic biphasic models were used for comparison with predictions from the current model. In the superficial zone, cell shapes changed from rounded to elliptic after free swelling. The stresses and strains as well as fluid flow in cells were greatly affected by the modulus of the collagen network. The fixed charge density of the chondrocytes, pericellular matrix, and extracellular matrix primarily affected the aspect ratios (height/ width) and the solid matrix stresses of cells. The mechanical responses of the cells were strongly location and time dependent. The current model highlights that the collagen orientation and the depth-dependent negative fixed charge densities of articular cartilage have a great effect in modulating the mechanical environment in the vicinity of chondrocytes, and it provides an important improvement over earlier models in describing the possible pathways from loading of articular cartilage to the mechanical and biological responses of chondrocytes