The sensitivity of articular chondrocytes to dynamic mechanical stimulation
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Chondrocyte sensitization and desensitization to mechanical stimuli are complex phenomena that can limit the effectiveness of mechanical stimulation in cartilage tissue engineering. The studies in this thesis aim to provide a more complete understanding of chondrocyte mechanical sensitivity as well as to develop new methods to aid in the successful use of dynamic compressive stimulation for tissue engineering applications. Through the examination of the durations of dynamic compressive loading, it was observed that a minimum amount of stimulation was required to elicit an anabolic response, but desensitization could quickly be reached with increased loading cycles. These anabolic responses could be predicted through the observation of calcium signaling, where an increase in intracellular calcium signaling levels correlated with an anabolic response. Calcium signaling could also be used to predict the wait time needed between successive applications of stimuli, where a return to baseline signaling levels indicated a full recovery of mechanosensitivity. To maintain mechanosensitivity throughout loading and to mitigate load-induced desensitization, which could negatively impact the anabolic response to mechanical stimuli, stochastic resonance in the form of superimposed random vibrations was investigated. In younger cells, stochastic resonance was able to improve cellular sensitivity and elicit further increases in matrix synthesis. Load-induced desensitization was also limited by stochastic resonance, allowing the cells to remain sensitive to increased loading durations. The recovery rate also appeared to be decreased by stochastic resonance indicating that less time would be required between successive applications of stimuli. In older cells which are normally insensitive to mechanical stimuli, stochastic resonance was able to induce sensitivity resulting in a positive anabolic response. The beneficial effects of stochastic resonance were able to be maintained over long term culture, where matrix accumulation was enhanced through the increased production of collagen and the mitigation of proteoglycan loss during dynamic compressive loading. Therefore the overall positive effects of stochastic resonance observed in this thesis indicate that it can be a valuable tool for the successful application of mechanical stimuli to engineered cartilage constructs.