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 can induce...
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| Format: | Thesis |
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Massachusetts Institute of Technology
2022
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| Online Access: | https://hdl.handle.net/1721.1/144504 |
| _version_ | 1826201205713403904 |
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| author | Varela Farías, Claudia Elena |
| author2 | Roche, Ellen T. |
| author_facet | Roche, Ellen T. Varela Farías, Claudia Elena |
| author_sort | Varela Farías, Claudia Elena |
| collection | MIT |
| description | 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 can induce 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 bridge-to-destination. Early interventions after MI to reduce adverse remodeling and prevent HF entirely have been developed but have yet to be translated to the clinic.
The main goal of this thesis is to develop implantable devices that directly modify the biological and/or mechanical environment of the recently infarcted heart to overcome the limitations associated with HF prevention strategies.
First, I optimize an implantable reservoir system that enables localized, multi-dose delivery of regenerative bioagents—previously necessitating multiple direct cardiac injections. After demonstrating that therapy transport from the reservoir is attenuated but not entirely impeded after fibrotic encapsulation in vivo, I introduce mechanical actuation as a strategy to improve transport from the system. Finally, our system is used to characterize how different dosing regimens of FSTL1, a regenerative protein, influence cardiac function and healing, demonstrating that three doses of FSTL1 has a more pronounced functional benefit than a regimen with less doses.
Second, I develop a sutureless patch platform whose mechanical behavior can be tuned to modulate cardiac biomechanics when attached to the heart. First, the in vivo performance of a bioadhesive hydrogel is optimized to allow for 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 achieve variable modulation of 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. |
| first_indexed | 2024-09-23T11:48:11Z |
| format | Thesis |
| id | mit-1721.1/144504 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:48:11Z |
| publishDate | 2022 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1445042022-08-30T03:38:40Z Device-Enabled Biomechanical Modulation of the Infarcted Heart Varela Farías, Claudia Elena Roche, Ellen T. Harvard-MIT Program in Health Sciences and Technology 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 can induce 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 bridge-to-destination. Early interventions after MI to reduce adverse remodeling and prevent HF entirely have been developed but have yet to be translated to the clinic. The main goal of this thesis is to develop implantable devices that directly modify the biological and/or mechanical environment of the recently infarcted heart to overcome the limitations associated with HF prevention strategies. First, I optimize an implantable reservoir system that enables localized, multi-dose delivery of regenerative bioagents—previously necessitating multiple direct cardiac injections. After demonstrating that therapy transport from the reservoir is attenuated but not entirely impeded after fibrotic encapsulation in vivo, I introduce mechanical actuation as a strategy to improve transport from the system. Finally, our system is used to characterize how different dosing regimens of FSTL1, a regenerative protein, influence cardiac function and healing, demonstrating that three doses of FSTL1 has a more pronounced functional benefit than a regimen with less doses. Second, I develop a sutureless patch platform whose mechanical behavior can be tuned to modulate cardiac biomechanics when attached to the heart. First, the in vivo performance of a bioadhesive hydrogel is optimized to allow for 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 achieve variable modulation of 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. Ph.D. 2022-08-29T15:51:59Z 2022-08-29T15:51:59Z 2022-05 2022-06-09T20:52:49.413Z Thesis https://hdl.handle.net/1721.1/144504 0000-0001-8082-092X In Copyright - Educational Use Permitted Copyright MIT http://rightsstatements.org/page/InC-EDU/1.0/ application/pdf Massachusetts Institute of Technology |
| spellingShingle | Varela Farías, Claudia Elena Device-Enabled Biomechanical Modulation of the Infarcted Heart |
| title | Device-Enabled Biomechanical Modulation of the
Infarcted Heart |
| title_full | Device-Enabled Biomechanical Modulation of the
Infarcted Heart |
| title_fullStr | Device-Enabled Biomechanical Modulation of the
Infarcted Heart |
| title_full_unstemmed | Device-Enabled Biomechanical Modulation of the
Infarcted Heart |
| title_short | Device-Enabled Biomechanical Modulation of the
Infarcted Heart |
| title_sort | device enabled biomechanical modulation of the infarcted heart |
| url | https://hdl.handle.net/1721.1/144504 |
| work_keys_str_mv | AT varelafariasclaudiaelena deviceenabledbiomechanicalmodulationoftheinfarctedheart |