Progress Towards a Higher Throughput Uniaxial Stretch Platform with Tunable Stiffness for Mechanobiology Experiments Public
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Calcific aortic valve disease (CAVD) is a disease in which the heart valve leaflets undergo calcification an eventually lose the ability to open and close. Currently the only treatment options for this disease are surgical. Mechanical factors are very important in the progression of CAVD. Previous work in our lab has modeled this disease by micropatterning circular aggregates of valvular interstitial cells into circular aggregates on a tunable stiffness substrate. Calcification and apoptosis (which is a cause of calcification) were measured in this model and found to be higher in the center of the aggregates and lower around the edges of the aggregates. Stresses in the aggregate model have been found to be higher on the edge of the aggregates and lower in the centers. We hypothesize that the lower stress state of cells in the center of the aggregates is responsible for the higher calcification and apoptosis. One way to test this is to apply cyclic stretch, which has been shown to raise the stress in the center of the aggregates.The goal of this project is to design an experimental system to apply cyclic stretch to aggregates micropatterned onto a tunable stiffness substrate. Different micropatterning techniques which pattern collagen onto polyacrylamide are attempted and evaluated, along with techniques to bind polyacrylamide to PDMS to enable the application of stretch. Experiments with stretchable micropatterned aggregates are performed in order to validate this system. A technique to polymerize polyacrylamide on a commercially available stretchable multi-well silicone plate is optimized and these gels are characterized for their storage modulus and surface features.
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