THEREPI: A therapeutic epicardial reservoir for the treatment of cardiac disease
Citation:
WHYTE, WILLIAM, THEREPI: A therapeutic epicardial reservoir for the treatment of cardiac disease, Trinity College Dublin.School of Engineering, 2019Download Item:
Abstract:
The clinical translation of regenerative therapy for the diseased heart, whether in the form of cells, macromolecules or small molecules, is hampered by several factors: the poor retention and short biological half-life of the therapeutic agent, the adverse side effects from systemic delivery, and difficulties with the administration of multiple doses. Here, we report the development, manufacturing processes and pre-clinical application of a therapeutic epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium via a biomaterial-based reservoir connected to a subcutaneous port.
In a myocardial infarct rodent model, we show that repeated administration of cells over a four-week period using the epicardial reservoir provided functional benefits in ejection fraction, fractional shortening and stroke work, compared to a single injection of cells and to no treatment.
Finally, in pursuit of a multimodal delivery system that that can deliver biological therapy with precise spatial and temporal control, we couple the therapeutic reservoir with a pneumatic soft robotic actuator. Using this approach, we demonstrate controlled drug release by altering the compressive stimulus and the biomaterial/cargo interaction.
This work has important practical and translational implications; preclinical use of the system as a research model may elucidate new insights into regenerative cardiac therapy, highlight the synergistic benefits of a holistic multi-modal approach and ultimately progress experimental therapies towards clinical use and improve patient outcomes.
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APPROVED
Author: WHYTE, WILLIAM
Advisor:
Murphy, BrucePublisher:
Trinity College Dublin. School of Engineering. Discipline of Mechanical & Manuf. EngType of material:
ThesisCollections
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Replenishable cell deliveryMetadata
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