The development of 3-D, in vitro, endothelial culture models for the study of coronary artery disease

The response of the vascular endothelium to wall shear stress plays a central role in the development and progression of atherosclerosis. Current studies have investigated endothelial response using idealized in vitro flow chambers. Such cell culture models are unable to accurately replicate the complex in vivo wall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both simplified/tubular and anatomically realistic in vitro endothelial flow models of the human right coronary artery. A post-mortem vascular cast of the human left ventricular outflow tract was used to create geometrically accurate silicone elastomer models. Straight, tubular models were created using a custom made mold. Following the culture of human abdominal aortic endothelial cells within the inner lumen, cells were exposed to steady flow (Re = 233) for varying time periods. The resulting cell morphology was analyzed in terms of shape index and angle of orientation relative to the flow direction. In both models a progressive elongation and alignment of the endothelium in the flow direction was observed following 8, 12, and 24 hours. This change, however, was significantly less pronounced in the anatomical model (as observed from morphological variations indicative of localized flow features). Differences were also observed between the inner and outer walls at the disease-prone proximal region. Since morphological adaptation is a visual indication of endothelial shear stress activation, the use of anatomical models in endothelial genetic and biochemical studies may offer better insight into the disease process

Local mechanical and structural properties of healthy and diseased human ascending aorta tissue

Objective: This study investigates the mechanics and histology of healthy and dilated human ascending aortas (AA). The regional variation in mechanical response and tissue structure were compared. Methods: Rings of human AA from healthy (n=5), dilated tricuspid aortic valve (TAV, n=5), and dilated bicuspid aortic valve (BAV, n=6) patients were mechanically tested. Each aortic ring was sectioned into quadrants\u2014anterior, posterior, medial (inner curvature) and lateral (outer curvature). Low- and high-stress elastic moduli were calculated from the equibiaxial stress strain curve to determine the local mechanical properties. Histological analysis was used to quantify the percent composition of elastin, collagen, and smooth muscle cells. Results: BAV tissue was thinnest and contained the largest percent composition of collagen. Both TAV and BAV tissue had significantly less elastin than healthy tissue. At low strain in the circumferential direction, TAV tissue was on average the least stiff. The elastic modulus was dependent on quadrant and tissue type but not direction (isotropic). Generally, the lateral quadrant tissue was the stiffest and the medial quadrant the least stiff. There were no apparent local variations in the tissue histology. Conclusions: Local variations in tissue thickness and mechanical properties were evident in all samples analyzed and may be linked to the type of aortic valve present.Peer reviewed: YesNRC publication: N

Miktoarm star conjugated multifunctional gold nanoshells: Synthesis and an evaluation of biocompatibility and cellular uptake

Biocompatible multifunctional gold nanoshells with imaging, stealth/aqueous solubility and therapeutic capabilities show high accumulation into endothelial cells.</p