Xuefeng Zhao

Biaxial deformation of collagen and elastin fibers in coronary adventitia

The microstructural deformation-mechanical loading relation of the blood vessel wall is essential for understanding the overall mechanical behavior of vascular tissue in health and disease. We employed simultaneous mechanical loading-imaging to quantify in situ deformation of individual collagen and elastin fibers on unstained fresh porcine coronary adventitia under a combination of vessel inflation and axial extension loading. Specifically, the specimens were imaged under biaxial loads to study microscopic deformation-loading behavior of fibers in conjunction with morphometric measurements at the zero-stress state. Collagen fibers largely orientate in the longitudinal direction, while elastin fibers have major orientation parallel to collagen, but with additional orientation angles in each sublayer of the adventitia. With an increase of biaxial load, collagen fibers were uniformly stretched to the loading direction, while elastin fibers gradually formed a network in sublayers, which strongly depended on the initial arrangement. The waviness of collagen decreased more rapidly at a circumferential stretch ratio of λθ = 1.0 than at λθ = 1.5, while most collagen became straightened at λθ = 1.8. These microscopic deformations imply that the longitudinally stiffer adventitia is a direct result of initial fiber alignment, and the overall mechanical behavior of the tissue is highly dependent on the corresponding microscopic deformation of fibers. The microstructural deformation-loading relation will serve as a foundation for micromechanical models of the vessel wall.

Microstructural constitutive model of active coronary media.

Although vascular smooth muscle cells (VSMCs) are pivotal in physiology and pathology, there is a lack of detailed morphological data on these cells. The objective of this study was to determine dimensions (width and length) and orientation of swine coronary VSMCs and to develop a microstructural constitutive model of active media. The dimensions, spatial aspect ratio and orientation angle of VSMCs measured at zero-stress state were found to follow continuous normal (or bimodal normal) distributions. The VSMCs aligned off circumferential direction of blood vessels with symmetrical polar angles 18.7° ± 10.9°, and the local VSMC deformation was affine with tissue-level deformation. A microstructure-based active constitutive model was developed to predict the biaxial vasoactivity of coronary media, based on experimental measurements of geometrical and deformation features of VSMCs. The results revealed that the axial active response of blood vessels is associated with multi-axial contraction as well as oblique VSMC arrangement. The present morphological database is essential for developing accurate structural models and is seminal for understanding the biomechanics of muscular vessels.

Biaxial vasoactivity of porcine coronary artery

The passive mechanical properties of blood vessel mainly stem from the interaction of collagen and elastin fibers, but vessel constriction is attributed to smooth muscle cell (SMC) contraction. Although the passive properties of coronary arteries have been well characterized, the active biaxial stress-strain relationship is not known. Here, we carry out biaxial (inflation and axial extension) mechanical tests in right coronary arteries that provide the active coronary stress-strain relationship in circumferential and axial directions. Based on the measurements, a biaxial active strain energy function is proposed to quantify the constitutive stress-strain relationship in the physiological range of loading. The strain energy is expressed as a Gauss error function in the physiological pressure range. In K(+)-induced vasoconstriction, the mean ± SE values of outer diameters at transmural pressure of 80 mmHg were 3.41 ± 0.17 and 3.28 ± 0.24 mm at axial stretch ratios of 1.3 and 1.5, respectively, which were significantly smaller than those in Ca(2+)-free-induced vasodilated state (i.e., 4.01 ± 0.16 and 3.75 ± 0.20 mm, respectively). The mean ± SE values of the inner and outer diameters in no-load state and the opening angles in zero-stress state were 1.69 ± 0.04 mm and 2.25 ± 0.08 mm and 126 ± 22°, respectively. The active stresses have a maximal value at the passive pressure of 80-100 mmHg and at the active pressure of 140-160 mmHg. Moreover, a mechanical analysis shows a significant reduction of mean stress and strain (averaged through the vessel wall). These findings have important implications for understanding SMC mechanics.

Two-layer model of coronary artery vasoactivity

Since vascular tone is regulated by smooth muscle cells in the media layer, a multilayer mechanical model is required for blood vessels. Here, we performed biaxial mechanical tests in the intima-media layer of right coronary artery to determine the passive and active properties in conjunction with the passive properties of adventitia for a full vessel wall model. A two-layer (intima-media and adventitia) model was developed to determine the transmural stress and stretch across the vessel wall. The mean ± SE values of the outer diameters of intima-media layers at transmural pressure of 60 mmHg in active state were 3.17 ± 0.16 and 3.07 ± 0.18 mm at axial stretch ratio of 1.2 and 1.3, respectively, which were significantly smaller than those in passive state (i.e., 3.62 ± 0.19 and 3.49 ± 0.22 mm, respectively, P < 0.05). The inner and outer diameters in no-load state of intima-media layers were 1.17 ± 0.09 and 2.08 ± 0.09 mm, respectively. The opening angles in zero-stress state had values of 159 ± 21° for intima-media layers and 98 ± 15° for adventitia layers, which suggests a residual strain between the two layers. There were slightly decreased active circumferential stresses (<10%), but significantly decreased active axial stresses (>25%) in the intima-media layer compared with those in the intact vessel. This suggests that the adventitia layer affects vascular contraction. The two-layer analysis showed that the intima-media layer bears the majority of circumferential tensions, in contrast to the adventitia layer, while contraction results in decreased stress and stretch in both layers.

Microstructure-Based Constitutive Models for Coronary Artery Adventitia

A structure-based constitutive model can accurately predict mechanical behaviors of blood vessels and enables a better understanding vascular patho-physiology. Most microstructural models assume affine deformation, i.e., fiber constituent deforms as the same as the tissue, and employ idealized microstructure due to the limited morphological data on vessel constituents. The goal of this chapter is to (1) introduce a new microstructural mechanical model that removes the affine deformation assumption and (2) to obtain quantitative microstructural data of coronary arteries. We develop a micromechanics-based constitutive model of fibrous tissue to take into consideration non-affine deformation that intrinsically induced by heterogeneous interactions between the constituents. Elastin fibers, cells, and ground substance are collectively considered as a solid-like matrix while collagen fibers is a reinforced phase. The model accounts for the waviness, orientation and spatial distributions of collagen fibers and provides a good prediction of macroscopic responses of the tissue which agree well with the finite element simulation results as a golden standard. We then use multiphoton microscopy to quantify the geometrical features of elastin and collagen fibers under mechanical loads. Simultaneous loading-imaging of the coronary adventitia allows measurements of the morphometry and in situ deformation of individual fibers. The population of fibers geometrical parameters including orientation angle, waviness, width and area fraction were measured at no-load state and the mechanical loading--deformation relation of fiber geometrical parameter were obtained as well. The present model and experimental studies are seminal for structural models and will lead to a better understanding of vascular biomechanics.

Microstructure and Mechanical Property of Glutaraldehyde-Treated Porcine Pulmonary Ligament

There is a significant need for fixed biological tissues with desired structural and material constituents for tissue engineering applications. Here, we introduce the lung ligament as a fixed biological material that may have clinical utility for tissue engineering. To characterize the lung tissue for potential clinical applications, we studied glutaraldehyde-treated porcine pulmonary ligament (n = 11) with multiphoton microscopy (MPM) and conducted biaxial planar experiments to characterize the mechanical property of the tissue. The MPM imaging revealed that there are generally two families of collagen fibers distributed in two distinct layers: The first family largely aligns along the longitudinal direction with a mean angle of θ = 10.7 ± 9.3 deg, while the second one exhibits a random distribution with a mean θ = 36.6 ± 27.4. Elastin fibers appear in some intermediate sublayers with a random orientation distribution with a mean θ = 39.6 ± 23 deg. Based on the microstructural observation, a microstructure-based constitutive law was proposed to model the elastic property of the tissue. The material parameters were identified by fitting the model to the biaxial stress-strain data of specimens, and good fitting quality was achieved. The parameter e0 (which denotes the strain beyond which the collagen can withstand tension) of glutaraldehyde-treated tissues demonstrated low variability implying a relatively consistent collagen undulation in different samples, while the stiffness parameters for elastin and collagen fibers showed relatively greater variability. The fixed tissues presented a smaller e0 than that of fresh specimen, confirming that glutaraldehyde crosslinking increases the mechanical strength of collagen-based biomaterials. The present study sheds light on the biomechanics of glutaraldehyde-treated porcine pulmonary ligament that may be a candidate for tissue engineering.

Growth and remodeling of canine common iliac vein in response to venous reflux and hypertension.

OBJECTIVE The passive properties of the venous wall are important for the compliance function of the venous system. The objective of this study was to quantify the passive biomechanical response and structural growth and remodeling of veins subjected to chronic venous reflux and hypertension. METHODS To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured in a canine model by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound was used to investigate the passive biomechanical response of both control common iliac veins (n = 9 dogs) and common iliac veins subjected to 8 weeks of venous reflux and hypertension (n = 9 dogs). The changes in vein wall thickness and constituent composition were quantified by multiphoton microscopy and histologic evaluation. RESULTS Biomechanical results indicate that the veins became less compliant when exposed to 8 weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be associated with a significant increase in wall thickness (P < .05) and collagen-to-elastin ratio (P < .05). After 8 weeks of chronic reflux and hypertension, the circumferential vein wall stress was significantly reduced (P < .05) because of wall thickening, although it was not restored to control levels. CONCLUSIONS The growth and remodeling of the venous wall reduces the wall stress, but the stress remains higher than at baseline at 8 weeks. The compliance of the veins also decreases because of the increase in wall thickness and remodeling of the microstructure of the venous wall. These findings provide insight into potential adaptations of the venous system in reflux and hypertension.

Simulation of LV pacemaker lead in marginal vein: potential risk factors for acute dislodgement.

Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design.

A novel arterial constitutive model in a commercial finite element package: Application to balloon angioplasty.

Recently, a novel linearized constitutive model with a new strain measure that absorbs the material nonlinearity was validated for arteries. In this study, the linearized arterial stress-strain relationship is implemented into a finite element method package, ANSYS, via the user subroutine USERMAT. The reference configuration is chosen to be the closed cylindrical tube (no-load state) rather than the open sector (zero-stress state). The residual strain is taken into account by analytic calculation and the incompressibility condition is enforced with Lagrange penalty method. Axisymmetric finite element analyses are conducted to demonstrate potential applications of this approach in a complex boundary value problem where angioplasty balloon interacts with the vessel wall. The model predictions of transmural circumferential and compressive radial stress distributions were also validated against an exponential-type Fung model, and the mean error was found to be within 6%.

Simulation of Mechanical Environment in Active Lead Fixation: Effect of Fixation Helix Size

The risk of myocardial penetration due to active-fixation screw-in type pacing leads has been reported to increase as the helix electrodes become smaller. In order to understand the contributing factors for lead penetration, we conducted finite element analyses of acute myocardial micro-damage induced by a pacemaker lead screw-in helix electrode. We compared the propensity for myocardial micro-damage of seven lead designs including a baseline model, three modified designs with various helix wire cross-sectional diameters, and three modified designs with different helix diameters. The comparisons show that electrodes with a smaller helix wire diameter cause more severe micro-damage to the myocardium in the early stage. The damage severity, represented by the volume of failed elements, is roughly the same in the middle stage, whereas in the later stage the larger helix wire diameter generally causes more severe damage. The onset of myocardial damage is not significantly affected by the helix diameter. As the helix diameter increases, however, the extent of myocardial damage increases accordingly. The present findings identified several of the major risk factors for myocardial damage whose consideration for lead use and design might improve acute and chronic lead performance.