Raymond P. Vito

Dynamic Mechanical Conditioning of Collagen-Gel Blood Vessel Constructs Induces Remodeling In Vitro

AbstractDynamic mechanical conditioning is investigated as a means of improving the mechanical properties of tissue-engineered blood vessel constructs composed of living cells embedded in a collagen-gel scaffold. This approach attempts to elicit a unique response from the embedded cells so as to reorganize their surrounding matrix, thus improving the overall mechanical stability of the constructs. Mechanical conditioning, in the form of cyclic strain, was applied to the tubular constructs at a frequency of 1 Hz for 4 and 8 days. The response to conditioning thus evinced involved increased contraction and mechanical strength, as compared to statically cultured controls. Significant increases in ultimate stress and material modulus were seen over an 8 day culture period. Accompanying morphological changes showed increased circumferential orientation in response to the cyclic stimulus. We conclude that dynamic mechanical conditioning during tissue culture leads to an improvement in the properties of tissue-engineered blood vessel constructs in terms of mechanical strength and histological organization. This concept, in conjunction with a proper biochemical environment, could present a better model for engineering vascular constructs.

Effect of Stenosis Asymmetry on Blood Flow and Artery Compression: A Three-Dimensional Fluid-Structure Interaction Model

AbstractA nonlinear three-dimensional thick-wall model with fluid-structure interactions is introduced to simulate blood flow in carotid arteries with an asymmetric stenosis to quantify the effects of stenosis severity, eccentricity, and pressure conditions on blood flow and artery compression (compressive stress in the wall). Mechanical properties of the tube wall are measured using a thick-wall stenosis model made of polyvinyl alcohal hydrogel whose mechanical properties are close to that of carotid arteries. A hyperelastic Mooney–Rivlin model is used to implement the experimentally measured nonlinear elastic properties of the tube wall. A 36.5% pre-axial stretch is applied to make the simulation physiological. The Navier–Stokes equations in curvilinear form are used for the fluid model. Our results indicate that severe stenosis causes critical flow conditions, high tensile stress, and considerable compressive stress in the stenosis plaque which may be related to artery compression and plaque cap rupture. Stenosis asymmetry leads to higher artery compression, higher shear stress and a larger flow separation region. Computational results are verified by available experimental data.

The distribution of strain in the human cornea

Experimental data on the mechanics of human cornea is meager and sometimes flawed. Moreover, questions regarding the correct material symmetry and the role of the fibrous microstructure are usually glossed over when mechanical models of the cornea and corneal shape changing procedures are presented. Accordingly, the deformation of 14 intact human corneas was measured for five pressures in the physiologic range (0, 5, 10, 25 and 45 cmH2O) by tracking small, self-adherent particles placed on their anterior surfaces. The meridional strains, calculated in five regions assuming axisymmetric deformation, are small; the average strain in the apical region being 1.14% at 45 cmH2O. Results also indicate that the strain distribution is unexpectedly nonuniform with statistically significant (p < 0.01, typical) variations between regions and a minimum occurring approximately half-way between apex and limbus. To better understand these results, a finite-element model (FEM) of the cornea was constructed and used to simulate the experiment. The heterogeneous model shows that our data may reflect the changing fiber orientation along a meridian suggested in the literature. The implications of a link between microstructure and mechanics are discussed in light of clinical procedures, such as radial keratotomy, the outcomes of which are dependent on corneal mechanical properties.

Two-Dimensional Stress-Strain Relationship for Canine Pericardium

Two-dimensional pseudoelastic mechanical properties of the canine pericardium were investigated in vitro. The pericardium was assumed to be orthotropic. The material symmetry axis was determined a priori and aligned with the stretching axis. Various biaxial stretching tests were then performed and a set of data covering a wide range of strains was constructed. This complete data set was fitted to a new exponential type constitutive model, and a set of true material constants was determined for each specimen. Using the constitutive model and the true material constants, the results from constant lateral force tests and constant lateral displacement tests were predicted and compared with experiment.

Mechanical Analysis of Heterogeneous, Atherosclerotic Human Aorta

An experimental technique was developed to determine the finite strain field in heterogeneous, diseased human aortic cross sections at physiologic pressures in vitro. Also, the distributions within the cross sections of four histologic features (disease-free zones, lipid accumulations, fibrous intimal tissue, and regions of calcification) were quantified using light microscopic morphometry. A model incorporating heterogeneous, plane stress finite elements coupled the experimental and histologic data. Tissue constituent mechanical properties were determined through an optimization strategy, and the distributions of stress and strain energy in the diseased vascular wall were calculated. Results show that the constituents of atherosclerotic lesions exhibit large differences in their bilinear mechanical properties. The distributions of stress and strain energy in the diseased vascular wall are strongly influenced by both lesion structure and composition. These results suggest that accounting for heterogeneities in the mechanical analysis of atherosclerotic arterial tissue is critical to establishing links between lesion morphology and the susceptibility of plaque to mechanical disruption in vivo.

Quantification of strains in biaxially tested soft tissues

A technique for the quantification of the strain field in the central region of biaxially tested planar soft tissues is presented. A vidicon-based image analysis system interfaced to a PDP 11/34 minicomputer is employed to track particles affixed to the specimen surface in real-time, from which the strains are inferred. Illustrative results are given for tests on excised canine pleural specimens on which four particles were affixed. The technique is applicable, however, to any planar soft tissue and any number of tracking particles. This procedure is recommended over previously used methods when testing anisotropic tissues.

A layered cylindrical shell model for an aorta

Abstract In this work, utilizing the result of the experiment that we conducted on a dogs upper thoracic aorta, a two layered cylindrical shell model is presented. A series of bi-axial tests were carried out on the specimens taken from the media and adventitia of an aortic segment and the stress-stretch relations were obtained. Considering the morphological structures of media and adventitia, an orthotropic elastic model for media and an isotropic elastic model for adventitia is presented. By comparing theoretical results and experimental measurements, the values of material constants appearing in the model have been determined. Finally, using the elastic models introduced, the inflation and axial extension of a layered cylindrical aorta was studied.

A Mechanical Model of the Cornea: The Effects of Physiological and Surgical Factors on Radial Keratotomy Surgery

A finite element-based computer simulation of radial keratotomy surgery was conducted to study, in particular, curvature changes of the central clear zone in human cornea under various physiological and surgical conditions. Corneal tissue was assumed to behave as a nearly incompressible, linear elastic, homogeneous, isotropic material undergoing small deformation. The Youngs modulus was determined by using the model to predict the surgical outcome of a representative patient. The results of the simulation are in qualitative agreement with clinical experience indicating the potential of finite element modeling as an aid to the surgeon in evaluating variables.

Arterial Wall Adaptation under Elevated Longitudinal Stretch in Organ Culture

AbstractArteries in vivo are subjected to large longitudinal stretch which may change significantly due to vascular disease and surgery. However, little is known about the effect of longitudinal stretch on vascular function and wall remodeling, although the effects of tensile and shear stress from blood pressure and flow have been well documented. To study the effect of longitudinal stretch on vascular function and wall remodeling, porcine carotid arteries were longitudinally stretched 20% more than in vivo for 5 days while being maintained in an ex vivo organ culture system under conditions of pulsatile flow at physiologic pressure. Vessel viability was demonstrated by strong vasomotor responses to norepinephrine (NE, 10-6M), carbachol (10-6M), and sodium nitroprusside (10-5M), as well as by dense staining for mitochondrial activity and a low occurrence of cell necrosis. Cell proliferation was examined by incorporation of bromodeoxyuridine (BrdU). Results showed that arteries maintain normal structure and viability after 5 days in organ culture. Both the stretched and control arteries demonstrated significant contractile responses. For example, both stretched and control arteries showed approximately 10% diameter contraction in response to NE. Stretched arteries contained 8% BrdU-positive cells compared to 5% in controls (p < 0.05). These results indicate that longitudinal stretch promotes cell proliferation in arteries while maintaining arterial function.

Mechanical determinants of plaque modeling, remodeling and disruption

The stability of the blood vessel wall and adequate perfusion of the tissues are maintained by structural adaptations to changes in wall shear and tensile stresses. These readjustments take the form of morphological reconstructions of vessel wall dimensions, composition and configuration. Altered flow results in adjustments to the diameter of vessels, which tend to restore wall shear stress to baseline values of 15‐20 dyn:cm 2 , while changes in vessel diameter or in fluid pressure produce altered mural tensile stresses which, in turn, generate corresponding changes in wall thickness and composition. During early development and growth, the proliferation of smooth muscle cells tends to correspond to an enlargement of the vessel diameter and an increase in wall volume, while matrix accumulation corresponds largely to tensile stress. After growth, the media and intima may both participate in these reactions. In conditions of decreased flow, intimal cell accumulation narrows the vessel lumen, thereby increasing wall shear stress until the baseline shear stress is restored. The intima then develops cellular and matrix features of the media.