While it is known that the aorta stiffens with location and age, little is known about the underlying mechanisms that govern these alterations. The purpose of this study was to investigate the relationship between the anisotropic biomechanical behavior and extracellular matrix microstructure of the human aorta and quantify how each changes with location and age. A total of 207 specimens were harvested from 5 locations (ascending n = 33, arch n = 38, descending n = 54, suprarenal n = 52, and abdominal n = 30) of 31 autopsy donor aortas (aged 3 days to 93 years). Each specimen underwent planar biaxial testing in order to derive quantitative biomechanical endpoints of anisotropic stiffness and compliance. Quantitative measures of fiber alignment and degree of fiber alignment were also generated on the same samples using a small-angle light scattering (SALS) technique. Circumferential and axial stiffening occurred with age and increased from the proximal to distal aorta, and the abdominal region was found to be more stiff than all others (p ≤ 0.006). Specimens from donors aged 61 and above were drastically more stiff than younger specimens (p < 0.001) and demonstrated greater circumferential compliance and axial stiffening (p < 0.001). Fiber direction for all ages and locations was predominantly circumferential (p < 0.001), and the degree of fiber alignment was found to increase with age (p < 0.001). Our results demonstrate that the aorta becomes more biomechanically and structurally anisotropic after age 60; with significant changes occurring preferentially in the abdominal aorta, these changes may play an important role in the predisposition of disease formation (e.g., aneurysm) in this region with age.
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Coronary artery bypass grafts used to treat coronary artery disease (CAD) often fail due to compliance mismatch. In this study, we have developed an experimental/computational approach to fabricate an acellular biomimetic hybrid tissue engineered vascular graft (TEVG) composed of alternating layers of electrospun porcine gelatin/polycaprolactone (PCL) and human tropoelastin/PCL blends with the goal of compliance-matching to rat abdominal aorta, while maintaining specific geometrical constraints. Polymeric blends at three different gelatin:PCL (G:PCL) and tropoelastin:PCL (T:PCL) ratios (80:20, 50:50, and 20:80) were mechanically characterized. The stress–strain data were used to develop predictive models, which were used as part of an optimization scheme that was implemented to determine the ratios of G:PCL and T:PCL and the thickness of the individual layers within a TEVG that would compliance match a target compliance value. The hypocompliant, isocompliant, and hypercompliant grafts had target compliance values of 0.000256, 0.000568, and 0.000880 mmHg−1, respectively. Experimental validation of the optimization demonstrated that the hypercompliant and isocompliant grafts were not statistically significant from their respective target compliance values (p-value = 0.37 and 0.89, respectively). The experimental compliance values of the hypocompliant graft were statistically significant than their target compliance value (p-value = 0.047). We have successfully demonstrated a design optimization scheme that can be used to fabricate multilayered and biomimetic vascular grafts with targeted geometry and compliance.
Abdominal aortic aneurysm (AAA), a localized dilation of the infrarenal aorta, represents a significant disease in the western population. There are approximately 200,000 patients in the US and 500,000 patients worldwide diagnosed with AAAs every year (Bosch, et al. 2001), and rupture of AAAs currently ranks as the 13th leading cause of death in the US. (Silverberg and Lubera 1987) In the past 30 years, the diagnosis of AAA has tripled in the Western world, and this will likely increase in the coming years as the average age of the population is increasing. (Bosch, et al. 2001)
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