MIT 4-270 and Zoom (see below for full information)
Device-enabled Biomechanical Modulation of the Infarcted Heart
Every 40 seconds someone in the United States suffers from a myocardial infarction (MI), and 86% of these patients survive this initial event. After an MI, a dense collagenous scar replaces damaged tissue and subsequently impedes cardiac function, prompts tissue remodeling, and ultimately induces heart failure (HF)—a prominent cause of long-term morbidity and mortality. Current clinical practice focuses on preventing or managing HF in these patients through medication and lifestyle changes, and if HF is severe, by implanting left ventricular assist devices to act as a bridge-to-transplant or destination. Early interventions after MI to reduce adverse remodeling and prevent HF altogether have been investigated but have yet to reach clinical translation.
The main goal of this thesis is to develop implantable devices that directly modify the biological or mechanical environment of recently infarcted heart to overcome existing limitations of promising HF prevention strategies.
First, I optimize an implantable reservoir system that enables localized, multi-dose delivery of regenerative bioagents—only previously achieved by direct cardiac injections. After showing that diffusion from the reservoir is possible after fibrotic encapsulation from a normal host response in vivo, I introduce mechanical actuation as a strategy to improve bioagent transport from the system. Finally, our system is used to characterize how different dosing regimens of follistatin-like 1 (FSTL1), a regenerative protein, influence cardiac function and healing, leading to the discovery that three FSTL1 doses are therapeutically superior.
Second, I develop a sutureless patch platform whose mechanical behavior can be tuned to modulate cardiac biomechanics when coupled to the heart. First, the in vivo performance of a bioadhesive hydrogel is optimized to enable atraumatic coupling and facilitate minimally invasive deployment of the patches. Then, I realize a patch design and fabrication workflow that allows for custom, tunable mechanical behavior of patches via 3D printing. Finally, I demonstrate that distinct patch designs can affect epicardial strain and ventricular hemodynamics in vivo.
In summary, this thesis presents versatile implantable device technologies that both circumvent existing limitations in biomechanical interventions for HF prevention in the recently infarcted heart and introduce novel therapeutic possibilities conducive for clinical translation.
Thesis Supervisor:
Ellen Roche, PhD
W.M. Keck Career Development Professor in Biomedical Engineering; Associate Professor of Mechanical Engineering and of the Institute for Medical Engineering & Science, MIT
Thesis Committee Chair:
Xuanhe Zhao, PhD
George N. Hatsopoulos (1949) Faculty Fellow; Professor of Mechanical Engineering and Civil and Environmental Engineering, MIT
Thesis Reader:
Robert F. Padera Jr., MD, PhD
Associate Professor, Pathology, Brigham and Women's Hospital and Harvard Medical School
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Claudia Elena Varela is inviting you to a scheduled Zoom meeting
Topic: Claudia Elena Varela PhD Thesis Defense
Time: Monday, May 2, 2022 02:30 PM Eastern Time (US and Canada)
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