College - Author 1
College of Engineering
Department - Author 1
Biomedical Engineering Department
Degree Name - Author 1
BS in Biomedical Engineering
Trevor Cardinal, College of Engineering, Biomedical Engineering Department
Peripheral arterial occlusive disease (PAOD) is characterized by atherosclerosis, which is the buildup of plaque, consisting largely of cholesterol, in the arterial walls. This plaque accumulation eventually blocks blood flow to the limbs, causing symptoms such as intermittent claudication and tissue death in cases of critical limb ischemia. The body compensates for the reduced perfusion by enlarging pre-existing bypass arteries, known as collaterals, in a process called arteriogenesis. However, in many cases, collateral networks constructed through arteriogenesis fail to enlarge sufficiently or function effectively in patients. Therefore, the development of a therapeutic intervention specifically targeting this process would offer a valuable solution for improving blood flow and facilitating tissue perfusion. Obesity and its comorbidities induce PAOD by promoting atherosclerosis, endothelial dysfunction, and impaired vascular function, so it is critical to analyze the degree of collateral remodeling following arteriogenesis in obese subjects to understand if the phenotype impacts the effectiveness of regenerative treatment. This study aims to determine whether myoblast implantation enhances collateral growth after induced ischemia in the hindlimbs of mice with diet-induced obesity (DIO) and in lean mice. PAOD was mimicked in all subjects by occluding blood flow in the femoral artery with a suture-based ligation. A thermally responsive, injectable polymer containing myoblasts, or no cells, was injected under the gracilis anterior, just deep to the targeted collateral. After 7 days post-operation, the polymer was removed and prepared for assessment. To assess the degree of collateral remodeling, perfusion fixation and vascular casting were performed, with subsequent removal of the anterior gracilis muscle for imaging and measuring vessel luminal/abluminal diameters and calculating arterial wall thickness. The analysis of the study revealed that there was no notable difference in collateral remodeling in the subjects that received the cell treatment and no difference in collateral diameters between the phenotypes (DIO and lean). However, the arterial wall thickness was larger in mice with DIO, regardless of the treatment received. Overall, the outcome of the experiment suggests that arteriogenesis was not enhanced by myoblast implantation in obese subjects.