Development of a microgel-based extracellular vesicle delivery system for heart repair
File(s)
Author(s)
Marijon, Camille
Type
Thesis
Abstract
Cardiovascular diseases are the primary cause of death globally, responsible for approximately 17.5 million deaths per year. In particular, myocardial infarction caused by the obstruction of a coronary artery can lead to heart failure. A growing number of studies have demonstrated that extracellular vesicles (EVs) exhibit great potential as cell-free cardioprotective agents, which could overcome many of the technical, ethical and regulatory hurdles associated with cell-based therapies. However, the beneficial effects of administered EVs are short-lived; a major limitation that could be circumvented using a material-based approach for increased retention and sustained release. Therefore, the main objective of this study was to develop a translational approach for repairing the infarcted heart, in the form of injectable, ‘off-the-shelf’ EV-loaded synthetic microgels. This platform was designed to improve EV stability and retention time at the site of administration, with sustained and environmentally-responsive release of EVs to the surrounding damaged tissue. Methods for fabricating monodisperse environmentally-sensitive microgels using a microfluidic-based platform were developed, and a first proof-of-concept of the feasibility of loading and releasing EVs from the microgels was demonstrated in vitro and in vivo.
Version
Open Access
Date Issued
2019-10
Date Awarded
2020-05
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Stevens, Molly
Sponsor
Rosetrees Trust
UK Regenerative Medicine Platform
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)