Biomedical Engineering

Fetal bovine serum has been shown to considerably inhibit phagocytosis of non-opsonized 2-µ m fluorescent latex beads by cultured macrophages IC-21. Phagocytic activity was assessed using fluorescent microscopy and specially devised ImageJ plugins. Phagocytosis percent, PP (percentage of the bead-containing cells in the cell population under study), and phagocytosis index, PI (mean number of beads per cell in the beadcontaining population), were about 2 times lower in the cells incubated in the presence of 10% serum as compared to the respective parameters for the cells incubated in serum-free medium (55 ± 5% vs. 92 ± 1% and 2.0 ± 0.2 vs. 4.3 ± 0.2 beads/cell). The effect of serum was dose-dependent. Albumin (10 mg/ml) did not mimic the effect of serum, suggesting that fatty acid extraction was not the cause of the serum-induced inhibition. Serum is a source of exogenous cholesterol, therefore we checked if cholesterol removal could stimulate phagocytosis. Cholesterol-sequestering agent methyl-β -cyclodextrin (m β CD) in concentrations of 5-7 mM indeed caused an increase of the phagocytic activity but at 10 mM exerted an inhibitory effect in serum-free medium. Connexin channel blocker carbenoxolone (CBX, 250-500 µ M) in most cases inhibited phagocytosis; the presence of serum or m β CD modulated the CBX effects. The data indicate an important role of serum in regulation of the macrophage phagocytic activity. Stimulating effect produced by serum removal may partly be accounted for by a decrease of cholesterol concentration, which in turn may alter the functioning of integral proteins involved in the mechanisms of phagocytosis.

One of the relevant phenomenon associated with in-stent restenosis in coronary arteries is an altered haemodynamics in the stented region. Computational fluid dynamics (CFD) offers the possibility to investigate the haemodynamics at a level of detail not always accessible within experimental techniques. CFD can quantify and correlate the local haemodynamics structures which might lead to in-stent restenosis. The aim of this work is to study the fluid dynamics of realistic stented coronary artery models which replicate the complete clinical procedure of stent implantation. Two cases of pathologic left anterior descending coronary arteries with their bifurcations are reconstructed from computed tomography angiography and conventional coronary angiography images. Results of wall shear stress and relative residence time show that the wall regions more prone to the risk of restenosis are located next to stent struts, to the bifurcations and to the stent overlapping zone for both investigated cases. Considering a bulk flow analysis, helical flow structures are generated by the curvature of the zone upstream from the stent and by the bifurcation regions. Helical recirculating microstructures are also visible downstream from the stent struts. This study demonstrates the feasibility to virtually investigate the haemodynamics of patient-specific coronary bifurcation geometries.

Computational models are used to study the combined effect of biomechanical and biochemical factors on coronary in-stent restenosis, which is a post-operative remodeling and regrowth of the stented artery tissue. More precisely, we address numerical simulations based on Navier-Stokes and mass transport equations to study the role of perturbed wall shear stresses and reduced oxygen concentration in a geometrical model reconstructed from a real porcine artery treated with a stent. Joining in vivo and in silico tools of investigation has multiple benefits in this case. On one hand, the geometry of the arterial wall and of the stent closely correspond to a real implanted configuration. On the other hand, the inspection of histological tissue samples informs us on the location and intensity of in-stent restenosis. As a result of that, we are able to correlate geometrical factors, such as the axial variation of the artery diameter and its curvature, the numerical quantification of biochemical stimuli, such as wall shear stresses, and the availability of oxygen to the inner layers of the artery, with the appearance of in-stent restenosis. This study shows that the perturbation of the vessel curvature could induce hemodynamic conditions that stimulate an undesired arterial remodeling.

Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed.