A Measure of Control for Secondary Cytokine-Induced Injury of Articular Cartilage: A Computational Study

In previous works, the author and collaborators establish a mathematical model for injury response in articular cartilage. In this paper we use mathematical software and computational techniques, applied to an existing model to explore in more detail how the behavior of cartilage cells is influenced by several of, what are believed to be, the most significant mechanisms underlying cartilage injury response at the cellular level. We introduce a control parameter, the radius of attenuation, and present some new simulations that shed light on how inflammation associated with cartilage injuries impacts the metabolic activity of cartilage cells. The details presented in the work can help to elucidate targets for more effective therapies in the preventative treatment of post-traumatic osteoarthritis

ONE-DIMENSIONAL BIOLOGICAL MODEL OF SYNOVIAL JOINTS REGENERATIVE REHABILITATION IN OSTEOARTHRITIS

This work is devoted to the study of a one-dimensional phenomenological model of a focal defect regenerative rehabilitation in the articular cartilage. The model is based on six differential equations in partial derivatives of the “Diffusion-Reaction” type, which was previously used by a number of authors to study cellular processes in various tissues under cell therapy conditions. To take into account the influence of moderate mechanical stimulation of immature tissue, an indirect approach was used, as a result of which some model parameters that directly affect cell proliferation and differentiation were varied considering experimental data. The results of  the model study  show that moderate stimulation of immature tissue in the early stages of repair the focal articular cartilage defect under conditions of cell therapy leads to an intensification of regenerative processes in the tissue and promotes more rapid formation of the extracellular matrix

Articular Contact Mechanics From an Asymptotic Modeling Perspective:a Review

In the present paper we review the current state-of-the-art in asymptotic modeling of articular contact. Particular attention has been given to the knee joint contact mechanics with a special emphasis on implications drawn from the asymptotic models, including average characteristics for articular cartilage layer. By listing a number of complicating effects such as transverse anisotropy, nonhomogeneity, variable thickness, nonlinear deformations, shear loading, and bone deformation, which may be accounted for by asymptotic modeling, some unsolved problems and directions for future research are also discussed

Computational Modelling of Tissue-Engineered Cartilage Constructs

Cartilage is a fundamental tissue to ensure proper motion between bones and damping of mechanical loads. This tissue often suffers damage and has limited healing capacity due to its avascularity. In order to replace surgery and replacement of joints by metal implants, tissue engineered cartilage is seen as an attractive alternative. These tissues are obtained by seeding chondrocytes or mesenchymal stem cells in scaffolds and are given certain stimuli to improve establishment of mechanical properties similar to the native cartilage. However, tissues with ideal mechanical properties were not obtained yet. Computational models of tissue engineered cartilage growth and remodelling are invaluable to interpret and predict the effects of experimental designs. The current model contribution in the field will be presented in this chapter, with a focus on the response to mechanical stimulation, and the development of fully coupled modelling approaches incorporating simultaneously solute transport and uptake, cell growth, production of extracellular matrix and remodelling of mechanical properties.publishe

Viscoelastic properties of the central region of porcine temporomandibular joint disc in shear stress-relaxation

In this study, shear relaxation properties of the porcine temporomandibular joint (TMJ) disc are investigated. Previous studies have shown that, in fatigue failure and damage of cartilage and fibrocartilage, shear loads could be one of the biggest contributors to the failure. The aim of the present study is to develop an evaluation method to study shear properties of the disc and to do a mathematical characterization of it. For the experiments, twelve porcine discs were used. Each disc was dissected from the TMJ and, then, static strain control tests were carried out to obtain the shear relaxation modulus for the central region of the discs. From the results, it was found that the disc presents a viscoelastic behavior under shear loads. Relaxation modulus decreased with time. Shear relaxation was 10% of the instantaneous stress, which implies that the viscous properties of the disc cannot be neglected. The present results lead to a better understanding of the discs mechanical behavior under realistic TMJ working conditions

Modeling the Dynamic Composition of Engineered Cartilage

Experimental studies indicate that culturing chondrocytes on biodegradable polymeric scaffolds may yield“engineered cartilage for the replacement of tissue lost to injury or diseases such as osteoarthritis. A method of estimating the outcome of cell-polymer cultures would aid in the design and evaluation of engineered tissue for therapeutic use. The goals of this project were to develop, validate, and apply first-generation mathematical models that describe the kinetics of extracellular matrix (ECM) deposition and scaffold degradation in cell-polymer constructs cultured in vitro. The ECM deposition model is based on a product-inhibition mechanism and predicts an asymptotic, exponential increase in the concentration of ECM molecules found in cartilage, including collagen and glycosaminoglycans (GAG). The scaffold degradation model uses first-order kinetics to describe the hydrolysis of biodegradable polyesters in systems not limited by diffusion. Each model was fit to published data describing the accumulation of GAG and collagen, as well as the degradation of poly glycolic acid (PGA) and poly lactic acid (PLA), respectively. As experimental validation, cell-polymer constructs (n = 24) and unseeded scaffolds (n = 24) were cultured in vitro, and biochemical assays for GAG and collagen content, as well as scaffold mass measurements, were performed at 1, 2, 4, 6, 8, or 10 weeks of culture (n = 8 per time point). The mathematical models demonstrate a moderate to strong goodness of fit with the previously published data and our experimental results (R2=0.75-0.99). These models were also combined to predict the temporal evolution of total construct mass with reasonable accuracy (30% RMS deviation). In ongoing work, estimates of biochemical composition derived from these models are being proposed to predict the mechanical properties and functionality of the constructs. This modeling scheme may be useful in elucidating more specific mechanisms governing ECM accumulation. Given their potential predictive power, these models may also reduce the cost of performing long-term culture experiments