Mechanotransduction in Engineered Cartilaginous Tissues: In Vitro Oscillatory Tensile Loading
Vanderploeg, Eric James
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Disease and degeneration of articular cartilage and fibrocartilage tissues severely compromise the quality of life for millions of people. Although current surgical repair techniques can address symptoms in the short term, they do not adequately treat degenerative joint diseases such as osteoarthritis. Thus, novel tissue engineering strategies may be necessary to combat disease progression and repair or replace damaged tissue. Both articular cartilage and the meniscal fibrocartilage in the knee joint are subjected to a complex mechanical environment consisting of compressive, shear, and tensile forces. Therefore, engineered replacement tissues must be both mechanically and biologically competent to function after implantation. The goal of this work was to investigate the effects of oscillatory tensile loading on three dimensional engineered cartilaginous tissues in an effort to elucidate important aspects of chondrocyte and fibrochondrocyte mechanobiology. To investigate the metabolic responses of articular chondrocytes and meniscal fibrochondrocytes to oscillatory tensile loading, various protocols were used to identify stimulatory parameters. Several days of continuously applied tensile loading inhibited extracellular matrix metabolism, whereas short durations and intermittently applied loading could stimulate matrix production. Subpopulations of chondrocytes, separated based on their zonal origin within the tissue, differentially responded to tensile loading. Proteoglycan synthesis was enhanced in superficial zone cells, but the molecular structure of these molecules was not affected. In contrast, neither total proteoglycan nor protein synthesis levels of middle and deep zone chondrocytes were substantially affected by tensile loading; however, the sizes of these new matrix molecules were altered. Up to 14 days of intermittently applied oscillatory tensile loading induced modest increases in construct mechanical properties, but longer durations adversely affected these mechanical properties and increased degradative enzyme activity. These results provide insights into cartilage and fibrocartilage mechanobiology by elucidating cellular responses to tensile mechanical stimulation, which previously had not been widely explored for these tissues. Understanding the role that mechanical stimuli such as tension can play in the generation of engineered cartilaginous tissues will further the goal of developing successful treatment strategies for degenerative joint diseases.