This project examines the progression of AAA by measuring elastin degradation and investigating blood-borne biomarkers. The collected data will enable the development of a device that tracks the progression of AAA and transmits the information to physicians.

This thesis explored a novel treatment approach for abdominal aortic aneurysms (AAAs) using sodium nitroprusside (SNP). We investigated the regenerative effects of SNP and SNP-releasing carriers in AAA models. Our findings showed that external SNP application strengthens elastic fibers and inhibits harmful enzymes (especially MMP2) through nitric oxide (NO). Using carriers for SNP resulted in reduced MMP2 and enhanced proteins crucial for artery health. In an artery model, SNP-releasing carriers supported cell growth, prevented enzyme activity, and promoted elastic fiber formation. Controlled SNP release from carriers suggests a longer-lasting treatment. This study introduces an efficient nanodrug carrier for targeted SNP delivery, marking a significant advancement in AAA treatment and providing insights into the role of NO in maintaining artery health.

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Abdominal aortic aneurysms (AAAs) involve the breakdown of elastic fibers in the aortic wall, and there's a lack of effective treatments to address this issue. Mesenchymal stem cells (MSCs) show potential in repairing tissue, but challenges in delivering them hinder their use. This study explores an alternative using tiny particles called extracellular nanovesicles (EVs), specifically exosomes, derived from MSCs. These EVs play a role in cell communication and carry active substances to stimulate tissue regeneration. The study investigates the effects of MSC-derived EVs on preventing tissue degradation and promoting regeneration in a culture model of aneurysmal smooth muscle cells. Additionally, the study explores how EVs influence signaling pathways related to tissue health. This research aims to find a cell-free approach for tissue repair with potential clinical applications.

Our experiments aim to test the broad hypothesis that MAPK inhibitors can be leveraged to modulate macrophage phenotype in abdominal aortic aneurysm (AAA) which can further promote improved extracellular matrix regeneration and elastin matrix homeostasis by aneurysmal smooth muscle cells. Testing of this hypothesis will include the coculture of human macrophages and human aneurysmal smooth muscle cells with subsequent analysis of cell behavior to determine the effect of MAPK inhibitor drugs.

This project focuses on finding an alternative treatment for Abdominal Aortic Aneurysms (AAAs). Currently, there are no effective treatments, and surgery is only performed when the aneurysm reaches a dangerous size. The proposed solution involves using biocompatible nanoparticles (NPs) to deliver drugs to the affected area, potentially slowing down aneurysm expansion and eliminating the need for surgery. The hypothesis is that NPs with higher aspect ratios can better bypass the damaged endothelium in AAAs. The project aims to demonstrate the targeting capabilities of these NPs through three steps:

1. Investigating the ability of spherical and rod-shaped PLGA NPs to pass through healthy and diseased endothelial cells in a 2D culture, simulating the aneurysmal environment.

2. Testing the passage capabilities of these NPs in 3D environments, using hydrogels of varying stiffness and cytokines to mimic diseased and healthy states. Flow conditions will be introduced using a microfluidic device.

3. Evaluating the potential of the designed NPs for drug delivery in vivo using a rat model, where fluorescently tagged NPs will be injected and monitored.

The ultimate goal is to develop a targeted drug delivery system leveraging the characteristics of the disrupted endothelium in AAAs, offering a non-surgical approach to treating this condition.