Heart valve cell biomechanics and mechanobiology

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Diseases of the heart valves are among the most frequent causes of heart disease in Canada. Diseased valves are often replaced surgically by artificial valves made of synthetic materials or animal tissue. A major drawback of artificial valves is that they do not grow or repair themselves once implanted in the body. These limitations have motivated tissue engineering efforts to make living replacement valves that are able to grow, adapt, and repair, just as normal, healthy valves do.      A key step to engineering functional heart valves is to mechanically stimulate the tissue while it is growing. This causes the cells within the tissue to make more tissue matrix, resulting in a valve with improved mechanical integrity. However, little is known about the response of individual valve cells to mechanical forces. If the relationship between the mechanical forces applied to a cell and the resulting mechanical and biological response were better understood, the effects of mechanical stimulation on valve tissue growth could be better predicted and controlled. Ultimately, this would lead to the design of engineered tissues with the same properties as healthy native valves.      The goal of this research is to develop and use computer-based simulations to predict the deformation or change in shape of individual cells within engineered valve tissue subjected to mechanical loading. The model will be supported by experimental measurements of the characteristic parameters that describe the mechanical properties of the cells. We will also measure gene expression of individual cells in response to mechanical stimulation and correlate the biological response with the deformation of the cell. This research will provide tools to study the biomechanical regulation of cells and ultimately may be used to design functional engineered tissues. While the focus of our research is valve tissue, the approaches we develop will be broadly applicable to the engineering of other tissues such as bone, cartilage, muscle, and blood vessels. This research will also train students in the fields of bioengineering, computational technologies, and tissue engineering.