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Aline L. Yonezawa
Ph.D. Proposal Presentation
Date: Friday, September 30
Time: 9:00 AM
Location: HSRB E160
Committee Members:
Michael E. Davis, PhD (Advisor)
K. Jane Grande-Allen, PhD
Wilbur Lam, MD, PhD
Wei Sun, PhD
Johnna S.Temenoff, PhD
Chunhui Xu, PhD
Engineering an aortic valve with cellular and mechanical functionality
Heart valve disease is an increasing clinical burden associated with high morbidity and mortality. Despite advances in tissue engineering heart valves (TEHV), a cellularized scaffold with physiological mechanical strength has yet to be developed. Here, we propose to replicate the microarchitecture and heterogeneity of the leaflet layers using 3D bioprinting in order to generate a valve with physiological mechanical properties and cellular activity. The overall hypothesis is we can generate induced valvular interstitial cells (iVICs) to create a living TEHV that mimics the structural and mechanical properties of native valves. We propose to differentiate human induced pluripotent stem cells (iPSCs) into iVICs using biochemical and mechanical cues. Then, using 3D bioprinting we will print layers of polycaprolactone (PCL) and poly(ethylene glycol) (PEG) containing our differentiated cells to recapitulate the three layers of the aortic valve leaflet. The inner structure will control the anisotropic properties of the valve. In addition, we also seek to use CT scans to generate patient-specific reconstructed 3D scaffolds that can be bioprinted with the leaflet microstructures. By mimicking the microstructure of the valve leaflet using biomaterials and integrating iVICs, we expect to generate a valve with mechanical properties and biological activity similar to native aortic valves.