Application of immunomodulatory biomaterials for cardiovascular repair
| dc.contributor.author | Yan, Weiang | |
| dc.contributor.examiningcommittee | Ghavami, Saeid (Human Anatomy and Cell Science) | |
| dc.contributor.examiningcommittee | Dixon, Ian (Physiology and Pathophysiology) | |
| dc.contributor.examiningcommittee | Kassiri, Zamaneh (University of Alberta) | |
| dc.contributor.supervisor | Dhingra, Sanjiv | |
| dc.contributor.supervisor | Arora, Rakesh C. | |
| dc.date.accessioned | 2025-01-10T14:50:27Z | |
| dc.date.available | 2025-01-10T14:50:27Z | |
| dc.date.issued | 2024-12-23 | |
| dc.date.submitted | 2024-12-24T02:25:05Z | en_US |
| dc.date.submitted | 2025-01-10T14:09:10Z | en_US |
| dc.degree.discipline | Physiology and Pathophysiology | |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | |
| dc.description.abstract | Cardiovascular diseases are the leading cause of death worldwide. Coronary artery disease, in particular, accounts for over 7 million deaths annually. Improvements in medical management has reduced the mortality of an acute myocardial infarction but simultaneously increased the prevalence of chronic heart failure. Currently available therapies for end-stage heart failure are limited, and novel therapies in functional myocardial regeneration are needed to address the irreversible loss of functional cardiomyocytes. This thesis focused on using biomaterials to tackle inflammation in the pathogenesis of heart failure to reduce myocardial injury and improve cardiac function. Inflammation plays a key role in cardiomyocyte loss, adverse remodeling, and failure of existing regenerative therapies. Biomaterials have emerged as promising tools to mediate the crosstalk between immune cells, stem and/or progenitor cells, and injured tissues to drive favourable pro-reparative immune responses. Chapter II is a literature review that highlighted the role of the immune system in cardiac injury, identified key signaling molecules that can be targeted for immunomodulation, and explored the role of mesenchymal stem cells in paracrine mediation of cardiac repair. Chapter III presented the development of a novel rosuvastatin-chitosan hydrogel that facilitated the delivery, survival, and immunomodulatory activity of allogeneic mesenchymal stem cells delivered to an acutely infarcted area of the myocardium. Chapter IV described the application and mechanistic characterization of novel two-dimensional transition metal carbides (MXenes) for targeted immunomodulation in a model of transplant vasculopathy. Finally, Chapter V described further rational design and improvements to the overall biocompatibility and function of the immunomodulatory MXene materials. Together, the work presented in this thesis represents several new biomaterials-based immunomodulatory platforms that can be used to facilitate cardiac repair after injury. | |
| dc.description.note | February 2025 | |
| dc.identifier.uri | http://hdl.handle.net/1993/38774 | |
| dc.language.iso | eng | |
| dc.rights | open access | en_US |
| dc.subject | Immunomodulation | |
| dc.subject | Cardiovascular Repair | |
| dc.subject | Biomaterials | |
| dc.subject | Stem Cell Therapy | |
| dc.title | Application of immunomodulatory biomaterials for cardiovascular repair | |
| dc.type | doctoral thesis | en_US |
| local.subject.manitoba | no | |
| oaire.awardNumber | MFE-171305 | |
| oaire.awardTitle | CIHR Fellowship | |
| project.funder.name | Canadian Institutes of Health Research |