Cyclic Mechanical Loading Enhances Transport of Antibodies Into Articular Cartilage

2016 ◽  
Vol 139 (1) ◽  
Author(s):  
Chris D. DiDomenico ◽  
Zhen Xiang Wang ◽  
Lawrence J. Bonassar
Keyword(s):  
Finite Element ◽  
Articular Cartilage ◽  
Mechanical Loading ◽  
Mechanical Stimulation ◽  
Mechanical Load ◽  
Linear Trend ◽  
Fluid Velocity ◽  
Cartilage Tissue ◽  
Clinical Value ◽  
Maximum Enhancement

The goal of this study was to characterize antibody penetration through cartilage tissue under mechanical loading. Mechanical stimulation aids in the penetration of some proteins, but this effect has not characterized molecules such as antibodies (>100 kDa), which may hold some clinical value for treating osteoarthritis (OA). For each experiment, fresh articular cartilage plugs were obtained and exposed to fluorescently labeled antibodies while under cyclic mechanical load in unconfined compression for several hours. Penetration of these antibodies was quantified using confocal microscopy, and finite element (FE) simulations were conducted to predict fluid flow patterns within loaded samples. Transport enhancement followed a linear trend with strain amplitude (0.25–5%) and a nonlinear trend with frequency (0.25–2.60 Hz), with maximum enhancement found to be at 5% cyclic strain and 1 Hz, respectively. Regions of highest enhancement of transport within the tissue were associated with the regions of highest interstitial fluid velocity, as predicted from finite-element simulations. Overall, cyclic compression-enhanced antibody transport by twofold to threefold. To our knowledge, this is the first study to test how mechanical stimulation affects the diffusion of antibodies in cartilage and suggest further study into other important factors regarding macromolecular transport.

scholarly journals Stress distribution in the knee joint in relation to tibiofemoral angle using the finite element method

2019 ◽  
Vol 252 ◽  
pp. 07007 ◽  
Author(s):  
Robert Karpiński ◽  
Łukasz Jaworski ◽  
Józef Jonak ◽  
Przemysław Krakowski
Keyword(s):  
Mechanical Properties ◽  
Finite Element Method ◽  
Finite Element ◽  
Articular Cartilage ◽  
Knee Joint ◽  
Cartilage Tissue ◽  
The Finite Element Method ◽  
Human Knee ◽  
Tibiofemoral Angle ◽  
Element Method

The article presents the results of a preliminary study on the structural analysis of the knee joint, considering changes in the mechanical properties of the articular cartilage of the joint. Studies have been made due to the need to determine the tension distribution occurring in the cartilage of the human knee. This distribution could be the starting point for designing custom made human knee prosthesis. Basic anatomy, biomechanical analysis of the knee joint and articular cartilage was introduced. Based on a series of computed tomography [CT] scans, the 3D model of human knee joint was reverse-engineered, processed and exported to CAD software. The static mechanical analysis of the knee joint model was conducted using the finite element method [FEM], in three different values of tibiofemoral angle and with varying mechanical properties of the cartilage tissue. Main conclusions of the study are: the capability to absorb loads by articular cartilage of the knee joint is preliminary determined as decreasing with increasing degenerations of the cartilage and with age of a patient. Without further information on changes of cartilage’s mechanical parameters in time it is hard to determine the nature of relation between mentioned capability and these parameters.

Influence of Calcified Cartilage Zone Permeability in Mechanical Behavior of Articular Cartilage: A Finite Element Study

2009 ◽  
Author(s):  
Ali Vahdati ◽  
Diane R. Wagner
Keyword(s):  
Mechanical Properties ◽  
Finite Element ◽  
Articular Cartilage ◽  
Mechanical Behavior ◽  
Independent Study ◽  
Cartilage Tissue ◽  
Fe Model ◽  
Mechanical State ◽  
Calcified Cartilage ◽  
Important Player

Articular cartilage (AC) disease and especially osteoarthrithis (OA) are debilitating conditions that are associated with huge social and economic burdens. To understand the factors involved in initiation and progression of OA, the mechanical state of the cartilage tissue must be first understood [1]. Biphasic and triphasic models developed by Mow and coworkers relate AC structure with its mechanical behavior and provided researchers with valuable models for AC biomechanics [2, 3]. Although much is known about AC and its mechanical properties, the zone of calcified cartilage (ZCC) has been sparsely studied. ZCC is very thin and highly interdigitated with subchondral bone (SB) which makes it very difficult to isolate for independent study [4]. It is well known that SB plays an important role in both initiation and/or progression of OA [5], thus ZCC may also be an important player in the pathology of the disease [6]. A few studies have investigated mechanical properties of ZCC, but conflicting results have been published on ZCC permeability. Although ZCC has been mainly assumed to be impermeable [7], recently Hwang et al. [8] suggested that ZCC may have even higher permeability than cartilage itself. We studied the effect of ZCC permeability on mechanical behavior of AC using a finite element (FE) model.

A Finite Element Model of Cell-Matrix Interactions to Study the Differential Effect of Scaffold Composition on Chondrogenic Response to Mechanical Stimulation

2011 ◽  
Vol 133 (4) ◽  
Author(s):  
Taly P. Appelman ◽  
Joseph Mizrahi ◽  
Dror Seliktar
Keyword(s):  
Finite Element ◽  
Finite Element Model ◽  
Mechanical Loading ◽  
Mechanical Stimulation ◽  
Element Model ◽  
Encapsulated Cells ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Model Predictions ◽  
Cell Matrix Interactions

Mechanically induced cell deformations have been shown to influence chondrocyte response in 3D culture. However, the relationship between the mechanical stimulation and cell response is not yet fully understood. In this study a finite element model was developed to investigate cell-matrix interactions under unconfined compression conditions, using a tissue engineered encapsulating hydrogel seeded with chondrocytes. Model predictions of stress and strain distributions within the cell and on the cell boundary were shown to exhibit space-dependent responses that varied with scaffold mechanical properties, the presence of a pericellular matrix (PCM), and the cell size. The simulations predicted that when the cells were initially encapsulated into the hydrogel scaffolds, the cell size hardly affected the magnitude of the stresses and strains that were reaching the encapsulated cells. However, with the inclusion of a PCM layer, larger cells experienced enhanced stresses and strains resulting from the mechanical stimulation. It was also noted that the PCM had a stress shielding effect on the cells in that the peak stresses experienced within the cells during loading were significantly reduced. On the other hand, the PCM caused the stresses at the cell-matrix interface to increase. Based on the model predictions, the PCM modified the spatial stress distribution within and around the encapsulated cells by redirecting the maximum stresses from the periphery of the cells to the cell nucleus. In a tissue engineered cartilage exposed to mechanical loading, the formation of a neo-PCM by encapsulated chondrocytes appears to protect them from initially excessive mechanical loading. Predictive models can thus shed important insight into how chondrocytes remodel their local environment in order to redistribute mechanical signals in tissue engineered constructs.

The Effect of Antibody Size and Mechanical Loading on Solute Diffusion Through the Articular Surface of Cartilage

2017 ◽  
Vol 139 (9) ◽  
Author(s):  
Chris D. DiDomenico ◽  
Andrew Goodearl ◽  
Anna Yarilina ◽  
Victor Sun ◽  
Soumya Mitra ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mechanical Loading ◽  
Articular Surface ◽  
Solute Diffusion ◽  
Cartilage Tissue ◽  
Tissue Penetration ◽  
Transport Enhancement ◽  
Healthy Cartilage ◽  
Heterogeneous Nature ◽  
Therapeutic Molecules

Because of the heterogeneous nature of articular cartilage tissue, penetration of potential therapeutic molecules for osteoarthritis (OA) through the articular surface (AS) is complex, with many factors that affect transport of these solutes within the tissue. Therefore, the goal of this study is to investigate how the size of antibody (Ab) variants, as well as application of cyclic mechanical loading, affects solute transport within healthy cartilage tissue. Penetration of fluorescently tagged solutes was quantified using confocal microscopy. For all the solutes tested, fluorescence curves were obtained through the articular surface. On average, diffusivities for the solutes of sizes 200 kDa, 150 kDa, 50 kDa, and 25 kDa were 3.3, 3.4, 5.1, and 6.0 μm2/s from 0 to 100 μm from the articular surface. Diffusivities went up to a maximum of 16.5, 18.5, 20.5, and 23.4 μm2/s for the 200 kDa, 150 kDa, 50 kDa, and 25 kDa molecules, respectively, from 225 to 325 μm from the surface. Overall, the effect of loading was very significant, with maximal transport enhancement for each solute ranging from 2.2 to 3.4-fold near 275 μm. Ultimately, solutes of this size do not diffuse uniformly nor are convected uniformly, through the depth of the cartilage tissue. This research potentially holds great clinical significance to discover ways of further optimizing transport into cartilage and leads to effective antibody-based treatments for OA.

Stress Evaluation of Articular Cartilage Chondrocyte Cell by Using Multi-Scale Finite Element Method and Smoothed Particle Hydrodynamics Method

2016 ◽  
Author(s):  
Kaito Nakahara ◽  
Yusuke Morita ◽  
Yoshihiro Tomita ◽  
Eiji Nakamachi
Keyword(s):  
Finite Element ◽  
Surface Layer ◽  
Articular Cartilage ◽  
Smoothed Particle Hydrodynamics ◽  
Cartilage Tissue ◽  
Fe Model ◽  
Stress Evaluation ◽  
Multi Scale ◽  
Particle Hydrodynamics ◽  
Smoothed Particle

The morphology and function of articular cartilage tissue is regenerated through the metabolic activity of cells stimulated by the mechanical loading. In this study, a biphasic multi-scale analyses scheme is adopted for stress evaluation occurred in the chondrocyte cell. The dynamic-explicit finite element (FE) method was employed for the solid phase and the smoothed particle hydrodynamics (SPH) method was used for the fluid phase. A macro-scale 3D human knee joint FE model was constructed based on magnetic resonance (MR) cross sectional images. Further, we derived the Representative volume element (RVE) based on the Multiphoton microscopy (MPM) observation to build a micro-scale FE model of cartilage tissue. We characterized three layers in the articular cartilage tissue. Parameters of the visco-anisotropic hyperelastic constitutive law and SPH models were determined using experimental results. Biphasic multi-scale FE and SPH analyses were carried out under the maximum loading condition in the normal walking motion. As a result, large flow velocity was observed around chondrocyte in the surface layer. The highest hydrostatic and shear stress occurred on chondrocyte in the surface layer. Numerical results shows a good agreement with experimental results.

Co-culture and Mechanical Stimulation on Mesenchymal Stem Cells and Chondrocytes for Cartilage Tissue Engineering

2020 ◽  
Vol 15 (1) ◽  
pp. 54-60
Author(s):  
Yawen Chen ◽  
Xinli Ouyang ◽  
Yide Wu ◽  
Shaojia Guo ◽  
Yongfang Xie ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Mechanical Stimulation ◽  
Therapeutic Option ◽  
Cartilage Damage ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
The Impact

Defects in articular cartilage injury and chronic osteoarthritis are very widespread and common, and the ability of injured cartilage to repair itself is limited. Stem cell-based cartilage tissue engineering provides a promising therapeutic option for articular cartilage damage. However, the application of the technique is limited by the number, source, proliferation, and differentiation of stem cells. The co-culture of mesenchymal stem cells and chondrocytes is available for cartilage tissue engineering, and mechanical stimulation is an important factor that should not be ignored. A combination of these two approaches, i.e., co-culture of mesenchymal stem cells and chondrocytes under mechanical stimulation, can provide sufficient quantity and quality of cells for cartilage tissue engineering, and when combined with scaffold materials and cytokines, this approach ultimately achieves the purpose of cartilage repair and reconstruction. In this review, we focus on the effects of co-culture and mechanical stimulation on mesenchymal stem cells and chondrocytes for articular cartilage tissue engineering. An in-depth understanding of the impact of co-culture and mechanical stimulation of mesenchymal stem cells and chondrocytes can facilitate the development of additional strategies for articular cartilage tissue engineering.

Sign in / Sign up

Export Citation Format

Share Document