Grant: Banting Postdoctoral Fellowship Program

Aortic aneurysm is an abnormal bulge in the aorta, the major blood vessel carrying oxygenated blood from the heart to the body. This bulge is caused by the weakened aortic wall that is pushed out by the pressure of the blood flowing through it. Aortic aneurysm is not symptomatic, and patients may not know they have an aneurysm until it ruptures causing death. Globally, aortic aneurysm causes ~150-200 thousand deaths/year. Currently, there is no effective (drug) treatment for aortic aneurysm. Corrective surgery is the only treatment for patients with very large or fast-growing aneurysms (high risk of rupture), but the surgery itself has risks. An aneurysmal aorta has a loss of cells that comprise the aortic wall (smooth muscle cells, fibroblasts) with degradation of the structural proteins (extracellular matrix, collagen, and elastin). Studies from the Kassiri lab and others have identified various molecules and mechanisms that underlie aortic aneurysm formation. Low efficacy for drug delivery to the aneurysm site and systemic side effects could be the reason for ineffective pharmacological treatments. We propose to optimize a collagen-based hydrogel biomaterial that will be enriched with cells present in healthy aortic wall (smooth muscle cells, fibroblasts) which will be placed over the aneurysmal (bulging) aorta. The collagen-based hydrogel will provide structural support (to prevent rupture) and a delivery platform for the cells to incorporate into the aortic wall and regenerate the weakened aortic wall. Preliminary data show that the surgical implantation of hydrogel in healthy mice promotes the integration of hydrogel into the aortic wall without any adverse reaction (inflammation), supporting our hypothesis. Findings from this project will provide a novel therapeutic approach to treat and perhaps reverse the structural damage in the aneurysmal aorta. The hydrogel cast can also serve as a platform for drug delivery in a personalized therapy approach.