Characterization of Heterogeneous Material Properties of Aorta Using Nanoindentation

Abstract

Arterial mechanical properties have received increasing attention in the past few decades due to their vast effect on predicting cardiovascular diseases and injuries. The heterogeneity of thoracic aortic tissue was characterized in terms of viscoelastic material properties and correlations were obtained between these properties and tissue morphology. Additionally, the effect of material preservation on the material properties was determined. Changes in the mechanical properties of porcine thoracic aorta wall in the radial direction were characterized using a quasi-linear viscoelastic modeling of nanoindentaiton tests. Two layers of equal thickness were mechanically distinguishable in descending aorta based on the radial variations in the instantaneous Young's modulus E and reduced relaxation function G(t). Overall, comparison of E and Ginf of the outer half (70.27±2.47 kPa and 0.35±0.01) versus the inner half (60.32±1.65 kPa and 0.33±0.01) revealed that the outer half was stiffer and showed less relaxation. The results were used to explain local mechanisms of deformation, force transmission, tear propagation and failure in arteries. A multimodal and multidisciplinary approach was adopted to characterize the transmural morphological properties of aorta. The utilized methods included histology and multi-photon microscopy for describing the wall micro-architecture in the circumferential-radial plane, and Fourier-Transform infrared imaging spectroscopy for determining structural protein, and total protein content. The distributions of these quantified properties across the wall thickness of the porcine descending thoracic aorta were characterized and their relationship with the mechanical properties was determined. It was revealed that there is an increasing trend in mechanical stiffness, Elastic lamella Density (ELD), Structural Protein (SPR), Total Protein (TPR), and Elastin and Collagen Circumferential Percentage (ECP and CCP) from inner layers toward the outer ones. Finally two larger regions with equal thickness (inner and outer halves) were determined based on cluster analysis results of ELD which were in agreement with the cluster analysis of instantaneous Young's modulus. Changes to the local viscoelastic properties of fresh porcine thoracic aorta wall due to three common storage temperatures (+4 oC, -20 oC and -80 oC) within 24 hours, 48 hours, 1 week and 3 weeks were characterized. The changes to both elastic and relaxation behaviors were investigated considering the multilayer, heterogeneous nature of the aortic wall. For +4 oC storage samples, the average instantaneous Young's modulus (E) decreased while their permanent average relaxation amplitude (Ginf) increased and after 48 hours these changes became significant (10%, 13% for E, Ginf respectively). Generally, in freezer storage, E increased and Ginf showed no significant change. In prolonged preservation (> 1 week), the results of +20 oC storage showed significant increase in E (20% after 3 weeks) while this increase for -80 oC was not significant, making it a better choice for tissue cold storage applications. Results from this dissertation present a substantial step toward the anatomical characterization of the aortic wall building blocks and establishing a foundation for understanding the role of microstructural components on the functionality of blood vessels. A better understanding of these relationships would provide novel therapeutic targets and strategies for the prevention of human vascular disease.