Browsing by Author "Han, Sang-Kuy"

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    Articular cartilage modeling in the 3-D patellofemoral joint contact
    (2003) Han, Sang-Kuy; Epstein, Marcelo
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    The effect of compressive loading magnitude on in situ chondrocyte calcium signaling
    (Biomech Model Mechanobiol, 2014-05) Herzog, Walter; Madden, Ryan M.J.; Han, Sang-Kuy
    Chondrocyte metabolism is stimulated by deformation and is associated with structural changes in the cartilage extracellular matrix (ECM), suggesting that these cells are involved in maintaining tissue health and integrity. Calcium signaling is an initial step in chondrocyte mechanotransduction that has been linked tomany cellular processes. Previous studies using isolated chondrocytes proposed loading magnitude as an important factor regulating this response. However, calcium signaling in the intact cartilage differs compared to isolated cells. The purpose of this study was to investigate the effect of loading magnitude on chondrocyte calcium signaling in intact cartilage. We hypothesized that the percentage of cells exhibiting at least one calcium signal increases with increasing load. Fully intact rabbit femoral condyle and patellar bone/cartilage samples were incubated in calcium-sensitive dyes and imaged continuously under compressive loads of 10–40% strain. Calcium signaling was primarily associated with the dynamic loading phase and greatly increased beyond a threshold deformation of about 10%nominal tissue strain. There was a trend toward more cells exhibiting calcium signaling as loading magnitude increased (p =0.133). These results provide novel information toward identifying mechanisms underlying calcium-dependent signaling pathways related to cartilage homeostasis and possibly the onset and progression of osteoarthritis.
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    In situ chondrocyte mechanics and numerical modeling
    (2009) Han, Sang-Kuy; Herzog, Walter
    Chondrocytes, the active cells in articular cartilage, are important in maintaining cartilage health and integrity by synthesizing the extracellular matrix. The mechanical environment of chondrocytes is thought to play a regulatory role in cell biosynthesis, and therefore is believed to be crucial for our understanding of cartilage adaptation and degeneration. Numerical modelling of chondrocytes and experimental tests on cartilage have been performed to elucidate the detailed transmission of load on articular cartilage to the cells. Much of the theoretical work has been based on the assumptions that articular cartilage is isotropic and homogeneous, which is known to be incorrect. In addition, most experimental studies have been performed on cartilage explants with the associated loss of tissue integrity and boundary conditions. Therefore, much of the current knowledge on chondrocyte mechanics is based on simplistic models and inappropriate tissue tests. The general aim of this study was to gain further insight into chondrocyte mechanics and its possible regulatory mechanisms for maintaining cartilage tissue. In order to accomplish this goal, we first developed an anisotropic and inhomogeneous articular cartilage model to study chondrocyte mechanics. The anisotropy and heterogeneity of cartilage was derived based on considerations of the micro-structural components of cartilage, particularly as they occur in the cell's vicinity. We found that for prescribed loading of the cartilage tissue, cells deform in a depth-dependent manner which is consistent with experimental studies. Specifically, we found that cell deformations are consistently smaller than tissue deformations because of the structural elements in the vicinity of the cell (the chondron), which appear to have a protective mechanical role that limits excessive cell strains. We then designed and developed a novel experimental loading system that allows for observation of cell deformations in the intact articular cartilage attached to its native bone. We systematically quantified chondrocyte deformations while applying controlled loads to healthy cartilage and cartilage from animals with early osteoarthritis. We found that chondrocyte deformations in the intact articular cartilage differed significantly from those described in explant tissues, and that early osteoarthritis changes cell deformations for given loading conditions in an unexpected way.