Aortic disease is a significant cause of death in developed countries. The most common forms of aortic disease are aneurysm, dissection, atherosclerotic occlusion and ageing-induced stiffening. The microstructure of the aortic tissue has been studied with great interest, because alteration of the quantity and/or architecture of the connective fibres (elastin and collagen) within the aortic wall, which directly imparts elasticity and strength, can lead to the mechanical and functional changes associated with these conditions. This review article summarizes the state of the art with respect to characterization of connective fibre microstructure in the wall of the human aorta in ageing and disease, with emphasis on the ascending thoracic aorta and abdominal aorta where the most common forms of aortic disease tend to occur.

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Objective One of the rate-limiting barriers within the field of vascular tissue engineering is the lengthy fabrication time associated with expanding appropriate cell types in culture. One particularly attractive cell type for this purpose is the adipose-derived mesenchymal stem cell (AD-MSC), which is abundant and easily harvested from liposuction procedures. However, even this cell type has its drawbacks including the required culture period for expansion which could pose risks of cellular transformation or contamination. Eliminating culture entirely would be ideal to avoid these concerns. In this study we utilized the raw population of cells obtained after digestion of human liposuction aspirates – known as the stromal vascular fraction (SVF) – as an abundant, culture-free cell source for tissue engineered vascular grafts (TEVG). Methods SVF cells and donor-paired cultured AD-MSCs were first assessed for their abilities to differentiate into vascular smooth muscle cells (SMCs) after angiotensin II stimulation and to secrete factors (e.g. conditioned media) that promote SMC migration. Next, both cell types were incorporated into TEVG scaffolds, implanted as an aortic graft in a Lewis rat model, and assessed for their patency and composition. Results In general, cells from human SVF were able to perform the same functions as AD-MSCs isolated from the same donor via culture expansion. Specifically, cells within the SVF performed two important functions, namely, they were able to differentiate into SMCs (SVF calponin expression: 16.4% ± 7.7 vs. AD-MSC: 19.9% ± 1.7) and could secrete pro-migratory factors (SVF migration rate relative to control: 3.1 ± 0.3 vs. AD-MSC: 2.5 ± 0.5). Additionally, SVF was also capable of being seeded within biodegradable, elastomeric, porous scaffolds that, when implanted in vivo for 8 weeks, generated patent TEVGs (SVF: 83% patency vs. AD-MSC: 100% patency) populated with primary vascular components (e.g. SMCs, endothelial cells, collagen, and elastin). Conclusion Human adipose tissue can be utilized as a culture-free cell source to create TEVGs, laying the groundwork for the rapid production of cell-seeded grafts.

Objective Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions. Methods Aortic tissue rings were obtained just distal to the sinotubular junction from patients with BAV or TAV undergoing elective aneurysm repair. They were sectioned into three circumferentially based regions according to adjacent aortic sinus segment (left coronary sinus [L], right coronary sinus [R], or noncoronary sinus [N]). Multiphoton microscopy was used to quantify and characterize the number of radially oriented elastin and collagen fibers. Results There were fewer radially oriented fibers in medial region N and medial-intimal region R of BAV-ATAAs when compared with TAV-ATAAs (medial region N, amplitude of angular undulation of elastin = 10.67° ± 1.35° vs 15.58° ± 1.91°; P = .041; medial-intimal region R, amplitude of angular undulation of elastin = 9.83° ± 0.83° vs 14.72° ± 1.64°; P = .015). Conversely, fibers became more radially oriented in the medial-intimal region L of BAV-ATAA when compared with TAV-ATAA (amplitude of angular undulation of collagen = 18.67° ± 0.95° vs 14.56° ± 1.37°; P = .041). Conclusions The differential pattern of fiber orientation noted between L and N-R regions help explain the unique pattern of greater curvature dilatation of BAV-ATAA. The distinctions noted in matrix microarchitecture may form the basis of differing aneurysm geometries and aortic wall integrities in ATAAs arising in these different valve morphologies.

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Tissue engineering, the use of a biodegradable scaffold with incorporation of a cellular source, particularly with mesenchymal stem cells (MSCs) has shown great promise in developing blood vessel grafts 1. Vascular tissue engineering not only combats the important clinical need for bypass grafts but also has the potential to advance current approaches by limiting intimal hyperplasia, thrombosis, and extended cell culture times 2–5. However, despite significant progress in this field, many preclinical evaluations of tissue engineered blood vessels (TEBVs) utilize cells from donor bases that are either non-human or from humans that are healthy 1. It is therefore unclear if cells from compromised donor populations are able to function effectively as the cellular component of TEBVs. This is particularly important for MSC-based TEBVs as they rely heavily on cellular processes to remodel in vivo to a native-like structure, with the current hypothesis being that MSCs stimulate the migration of smooth muscle cells (SMCs) from the adjacent vascular walls 6,7. While some studies have noted that cellular dysfunction exists with the presence of certain conditions 8–11, it is critically important for the field of TEBVs to evaluate human cells, specifically those from patients at high risk for cardiovascular disease such as diabetics and those of advanced age.

Aortic dissection is a life-threatening cardiovascular emergency with a high potential for death. It usually begins with an intimal tear which permits blood to enter the wall, split the media and create a false lumen, which can reenter the true lumen or exit through the adventitia causing complete rupture. A possible mechanism for dissection of ascending thoracic aortic aneurysm (ATAA) can be the occurrence of blood pressure-induced wall stresses in excess to the adhesive strength between the degenerated aortic wall layers.