| Cardiovascular disease is the leading cause of death in the United States. Atherosclerosis is a cardiovascular disease associated with the accumulation of materials such as lipids, calcifications, hematoma, and necrotic debris in the artery wall, resulting in lesions known as plaques. Plaques may cause stenosis, or a narrowing of the blood vessel lumen, and impinge on downstream blood flow. Clinical episodes more commonly result from fracture of plaques and subsequent release of debris which blocks smaller downstream arteries. Lesions with a high propensity for fracture are known as vulnerable plaques. Plaque vulnerability is thought to be highly dependent upon lesion composition and morphology. Accurate assessment of plaque vulnerability also depends on the mechanical properties of the different tissues in the plaque. However, to date there is limited information on the structure-property relations in atherosclerotic plaque tissues. The primary goal of this thesis was therefore to investigate the relationship between mechanical properties and tissue composition in atherosclerotic plaques. Because plaque tissue is very heterogeneous and contains diverse constituents, including lipids, calcifications, and fibrous tissue, a new approach was developed using nanoindentation and Fourier transform infrared spectroscopy (FTIR). Nanoindentation was selected for mechanical property measurements due to its ability to measure local material properties on the nanoscale. Biochemical analysis was performed using FTIR to provide semiquantitative measures of tissue composition (in particular, lipid and calcification content) for correlation to mechanical properties. Using these tools together, relationships were observed between the mechanical properties and the composition of atherosclerotic plaque tissue. In particular, the reduced moduli of the tissue samples were found to increase with increasing calcification content. While FTIR is a well-established technique for analysis of tissue composition, nanoindentation has only recently emerged in the biomaterials community. Numerous studies have been performed in bones and teeth, but limited work has been performed in soft tissues. Reported here are additional nanoindentation studies of a range of biological tissues, including trabecular bone, cartilage, and soft fibrous tissues such as healthy blood vessels and myocardial tissue. These studies provide reference materials for comparison to plaque tissue properties in addition to extending the applications of nanoindentation to soft biological tissues. |
