A link between stent radial forces and vascular wall remodeling: the discovery of an optimal stent radial force for minimal vessel restenosis.

Coronary and peripheral artery disease (PAD) continue to be primary causes of morbidity and mortality in western nations; percutaneous transluminal angioplasty (PTA) with stenting has become a popular treatment. Unfortunately, restenosis is a significant problem following intravascular stent placement. This study considers the contribution of stent forces in vascular stenosis and remodeling to develop an equation for identifying the optimal stent force. z-Type stents of three radial forces [low (3.4 N), high (16.4 N), and ultrahigh (19.4 N)] were deployed into the iliac arteries of a juvenile porcine model. Vessel diameters were measured before, after deployment, and again at 30 days. At 30 days animals were killed and the vessels fixed in situ. After implantation, there was a significant increase in total thickness and neointimal hyperplasia with increasing stent force. The model for vessel radius and experimental data was in agreement. The model shows that maximum late-term radius is achieved with a stent deployment stress of 480 kPa, which occurs at the end of the stress-strain curve nonlinear domain and beginning of the high-strain collagen domain. The results and calculations suggest that an optimal stent force exists that is subject to the geometry, structure, and mechanics of the target vessel. To achieve maximum late-term dilatation, stents should not produce stress in the vessel wall greater than the end of the transitional domain of the vessel's stress-strain curve. This finding is extremely important for vascular stent development and will be expanded to preliminary vessel wall injury and atherosclerotic models.

Interaction of vascular smooth muscle cells with collagen-impregnated embolization coils studied with a novel quantitative in vitro model.

BACKGROUND AND PURPOSE: Modifications of aneurysm occlusion devices and other biologically active molecules may reduce the risk of recanalization by promoting vascular cell migration, adhesion, and proliferation. Our purpose was to apply in vitro methods in the qualitative and quantitative analysis of vascular smooth muscle cell (VSMC) interactions with collagen-impregnated microcoils. METHODS: The adhesion of rat aortic VSMCs to collagen fiber bundles (CFBs), nitinol coils, and collagen-impregnated nitinol coils (CINCs) was examined by using an assay consisting of monopulse exposure to increasing concentrations of rat aortic VSMCs. Exposed devices were washed and examined by using confocal fluorescence microscopy. Adhesion coefficients, which quantitatively express the cell-binding quality of a surface, were determined by using a mathematical model for cell-device interactions. RESULTS: VSMCs, attached to devices, spread out and extended cytoplasmic projections over the contact surface. Cell distribution was random on CFBs and within interloop troughs on nitinol coils. On collagen-impregnated coils, VSMCs were selectively concentrated on the collagen between coil loops. The average adhesion coefficient was 25.0 for CFBs, 8.5 for CINCs (250-microm pitch), and 6.5 for nitinol coils. Adhesion coefficient differences for the three devices were significant (P =.044). CONCLUSION: The monopulse exposure assay is a simple and reproducible in vitro test that provides qualitative information about the morphology and topography of cell-device contacts and permits quantitative measurement of the intrinsic cell-binding quality of the test device. VSMCs exposed to collagen-impregnated microcoils selectively attach to collagen. Collagen enhances the rate of VSMC adhesion to embolic devices, and the degree of enhancement correlates with the surface area constituted by collagen.

Viscoelastic properties of self-assembled type I collagen fibers: molecular basis of elastic and viscous behaviors.

We have studied the strain rate dependence of incremental stress-strain curves of self-assembled type I collagen fibers in an effort to understand the molecular phenomena that contribute to the macroscopic mechanical behavior of tendons. Results of viscoelastic tests at strain rates between 10% and 1000% per min suggest that the slope of the elastic stress-strain curve is to a first approximation independent of strain rate while the slope of the viscous stress-strain curve increases with increased strain rate. After correction of the slope of the viscous stress-strain curve for the changes in strain rate, it is observed that the apparent viscosity decreases with increased strain rate. It is concluded that the approximate strain rate independence of the elastic spring constant of collagen is consistent with the spring-like behavior of the 12 flexible regions that make up the collagen D-period. These regions are poor in the rigid amino acid residues proline and hydroxyproline. In contrast, the thixotropy of collagen is consistent with the slippage of subfibrillar subunits during tensile deformation. It is hypothesized that at high strain rates subfibrillar subunits appear to "hydroplane" by each other on a layer of loosely bound water.

Mechanical behavior of vessel wall: a comparative study of aorta, vena cava, and carotid artery.

We have used incremental stress-strain curves to study the mechanical behavior of porcine aorta, carotid artery, and vena cava. Elastic and viscous stress-strain curves are composed of low and high strain regions that are approximately linear. Analysis of the low strain behavior is consistent with previous studies that suggest that the behavior is dominated by the behavior of elastic fibers, and that the collagen and elastic fibers are in parallel networks. At high strain, the behavior is different than that of skin where it is dominated by the behavior of the collagen fibers. The high strain behavior is consistent with a series arrangement of the collagen and smooth muscle; however, the arrangement of smooth muscle and collagen may be different in aorta than in the other vessels studied. It is concluded that the mechanical behavior of the vessel wall differs from the behavior of other extracellular matrices that do not contain smooth muscle. Our results indicate that at least some of the collagen fibrils in the media are in series with smooth muscle cells and this collagen-smooth muscle network is in parallel with parallel networks of collagen and elastic tissue in aorta, carotid artery, and vena cava. It is concluded that the series arrangement of collagen and smooth muscle may be important in mechanochemical transduction in vessel walls and that the exact quantity and arrangement of these components may differ in different vessels.