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dc.contributor.advisorMurphy, Bruce
dc.contributor.authorWHYTE, WILLIAM
dc.date.accessioned2019-05-13T08:51:29Z
dc.date.available2019-05-13T08:51:29Z
dc.date.issued2019en
dc.date.submitted2019
dc.identifier.citationWHYTE, WILLIAM, THEREPI: A therapeutic epicardial reservoir for the treatment of cardiac disease, Trinity College Dublin.School of Engineering, 2019en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/86761
dc.descriptionAPPROVEDen
dc.description.abstractThe 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.en
dc.language.isoenen
dc.publisherTrinity College Dublin. School of Engineering. Discipline of Mechanical & Manuf. Engen
dc.rightsYen
dc.subjectReplenishable cell deliveryen
dc.titleTHEREPI: A therapeutic epicardial reservoir for the treatment of cardiac diseaseen
dc.typeThesisen
dc.type.supercollectionthesis_dissertationsen
dc.type.supercollectionrefereed_publicationsen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnameDoctor of Philosophy (Ph.D.)en
dc.identifier.peoplefinderurlhttps://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:WWHYTEen
dc.identifier.rssinternalid203051en
dc.rights.ecaccessrightsopenAccess
dc.rights.restrictedAccessY
dc.date.restrictedAccessEndDate2021-03-01


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