Tissue-engineered polymers stimulate angiogenesis in infarcted myocardium

Abstract

The development and maintenance of a vascular network is critical to the growth and survival of a tissue and ultimately an organism. An understanding of the mechanisms which regulate angiogenesis within and surrounding currently used polymeric devices would contribute to the success of these implants by establishing methods to enhance tissue in-growth and new vessel development. Furthermore, tissue-engineering currently used polymers such as expanded polytetrafluoroethylene (ePTFE) may create an angiogenic material that can be used to induce new microvessel formation in infarcted myocardium. Myocardial infarcts represent a pathology that affects a large percentage of the patient population who suffer from coronary heart disease. Disease of the coronary vasculature can lead to narrowing of the coronary vasculature and result in regions of ischemia which can progress to infarction. Studies in this dissertation evaluate two different tissue-engineered polymer constructs for their ability to stimulate a new collateral network in infarcted myocardium. The results from these studies indicate that the tissue site of implantation is an important factor in influencing the healing response. Therefore, it is important to evaluate future polymer devices in tissues where the device will ultimately reside. Additionally, the physical and chemical characteristics of polymers were found to have a significant influence on the healing response. Furthermore, tissue-engineered polymer constructs stimulated a significant angiogenic response within infarcted myocardium. Tissue-engineered constructs that secreted soluble angiogenic agents were found to have the greatest depth of angiogenic effect into infarcted myocardium leading to the formation of arterioles, capillaries, and venules. Additionally, hearts treated with these devices demonstrated significantly greater left ventricular function in comparison to infarct-only hearts. Based on this work, it is apparent that tissue-engineered polymer constructs may have a future role as cardiac patches and thus provide the patient population with an additional therapy to revascularize infarcted cardiac tissues.