BIOMANUFACTURING METHODS FOR RECAPITULATING NATIVE-LIKE PROPERTIES IN TISSUE ENGINEERED HEART VALVES

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Heart valve disease is a large and growing burden on the global healthcare system. A wide range of patients are affected by complications due to heart valve disease. Currently, valve replacement is the only solution for severe cases of heart valve dysfunction. However, current prosthetic valve solutions do not have the ability to biologically respond to the environment that they are placed into. This leads to the need for anticoagulant medication or resizing surgeries if patients are still growing after the initial replacement. Tissue engineered valve replacements may offer the ability to implant a growing, remodeling, and adapting valve that could eliminate several of the downsides in current valve replacement methods, especially for young, growing patients. However, there are still many difficulties in creating a living, functional valve that replicates the geometry, function, and adaptability of a native valve. The work in this dissertation was intended to develop biomanufacturing methods that may be able to improve the function, mechanics, and remodeling of tissue engineered heart valves. A novel 3D printing method was developed to print complex curvature to develop specific mechanical properties as well as offer a way to create complex tissues such as heart valves (Chapter 2). Next, a method of using incremental stretch of fibrin tissues demonstrates that heart valve leaflet tissues can be strengthened while increasing their size in culture (Chapter 3). Finally, 3D printed collagen was introduced into the incremental stretch system in order to understand how multi-material tissues can be used to drive cell remodeling and alignment (Chapter 4). Overall, this body of work advances our understanding of biomanufacturing methods for heart valve tissue engineering by providing insight into how living, functional tissues can be created and conditioned. This work combines studies manufacturing, biomechanics, and mechanobiology in order to move closer to clinical applications of living heart valve tissue.
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Shepherd, Robert
Estroff, Lara