Journal
NATURE BIOMEDICAL ENGINEERING
Volume 2, Issue 6, Pages 416-428Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41551-018-0247-5
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Funding
- Wyss Institute for Biologically Inspired Engineering at Harvard University
- Institute for Medical Engineering Science at the Massachusetts Institute of Technology
- Wellcome Trust/Science Foundation Ireland/Health Research Board Seed Award in Science
- Government of Ireland Postdoctoral Award from Irish Research Council
- Science Foundation Ireland [SFI/12/RC/2278]
- Trinity College Dublin, Ireland
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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 and application of a therapeutic epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium via a polymer-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. The pre-clinical use of the therapeutic epicardial reservoir as a research model may enable insights into regenerative cardiac therapy, and assist the development of experimental therapies towards clinical use.
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