Effects of Intermittent Static and Dynamic Tension on Articular Chondrocytes in High Density Culture
Fan, Chung Yan
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Tissue engineering has the potential of becoming an effective approach for the replacement of articular cartilage. However, the problems of small tissue size and inadequate mechanical properties of the tissue have yet to be overcome. Mechanical stimulation of cartilaginous tissues is one method of accelerating chondrocyte proliferation and ECM synthesis. While the effects of compression and shear have been well studied, the effects of tension have received little attention. Based on the findings of previous mechanical stimulation studies and photographic evidence of tension acting in native articular cartilage in its physiological environment, it was hypothesized that intermittent applications of tensile strain can be used to stimulate cellular proliferation and ECM synthesis and thereby improve the size and mechanical properties of cartilaginous tissues. A loading fixture was constructed to apply biaxial tensile strains (BTS) to cartilaginous tissues grown in vitro. The optimal conditions for stimulating proliferation and ECM synthesis were found to be static tension (as opposed to dynamic tension), 3.8% radial and 2.1% circumferential strain magnitude for a 30 minute duration. Tissues subjected to BTS stimulation for 4 weeks at a frequency of once every 2-3 days had increased thickness, wet weight, and proteoglycan content, but had little effect on tissue mechanical properties. Tissues stimulated at a frequency of once per day over the same period had a negligible effect. A subsequent experiment confirmed that the effects of BTS stimulation on proliferation and ECM synthesis were dependent on load frequency, as well as culture media pH. The experimental results of this thesis suggest that the physical stretching of chondrocytes may have had more of an impact on stimulating proliferation and ECM synthesis than induced interstitial fluid flow. Chondrocytes also require a period of preconditioning before the stimulated effects occur, but too high of a loading frequency can cause possible desensitization and/or a catabolic response. Overall, the experiments were successful in identifying the stimulatory potential of tensile strains. However, further improvements must be made to the long-term effects on tissue mechanical properties before tension can be used as an effective stimulus to produce better quality in engineered cartilaginous tissues.