Boran Zhou

Cellularized microcarriers as adhesive building blocks for fabrication of tubular tissue constructs.

To meet demands of vascular reconstruction, there is a need for prosthetic alternatives to natural blood vessels. Here we explored a new conduit fabrication approach. Macroporous, gelatin microcarriers laden with human umbilical vein endothelial cells and aortic smooth muscle cells were dispensed into tubular agarose molds and found to adhere to form living tubular tissues. The ability of cellularized microcarriers to adhere to one another involved cellular and extracellular matrix bridging that included the formation of epithelium-like cell layers lining the lumenal and ablumenal surfaces of the constructs and the deposition of collagen and elastin fibers. The tubular tissues behaved as elastic solids, with a uniaxial mechanical response that is qualitatively similar to that of native vascular tissues and consistent with their elastin and collagen composition. Linearized measures of the mechanical response of the fabricated tubular tissues at both low and high strains were observed to increase with duration of static culture, with no significant loss of stiffness following decellularization. The findings highlight the utility of cellularized macroporous gelatin microcarriers as self-adhering building blocks for the fabrication of living tubular structures.

A mechanical argument for the differential performance of coronary artery grafts

Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted vessel making retention of graft patency dependent on chronic remodeling processes. The time course and extent to which remodeling restores vessel homeostasis will depend, in part, on the nature and magnitude of the mechanical disturbances induced upon transplantation. In this investigation, biaxial mechanical testing and histology were performed on the porcine left anterior descending artery (LAD) and analogs of common autografts, including the internal thoracic artery (ITA), radial artery (RA), great saphenous vein (GSV) and lateral saphenous vein (LSV). Experimental data were used to quantify the parameters of a structure-based constitutive model enabling prediction of the acute vessel mechanical response pre-transplantation and under coronary loading conditions. A novel metric Ξ was developed to quantify mechanical differences between each graft vessel in situ and the LAD in situ, while a second metric Ω compares the graft vessels in situ to their state under coronary loading. The relative values of these metrics among candidate autograft sources are consistent with vessel-specific variations in CABG clinical success rates with the ITA as the superior and GSV the inferior graft choices based on mechanical performance. This approach can be used to evaluate other candidate tissues for grafting or to aid in the development of synthetic and tissue engineered alternatives.

The biaxial active mechanical properties of the porcine primary renal artery

The mechanical response of arteries under physiological loads can be delineated into passive and active components. The passive response is governed by the load-bearing constituents within the arterial wall, elastin, collagen, and water, while the active response is a result of vascular smooth muscle cell (SMC) contraction. In muscular blood vessels, such as the primary renal artery, high SMC wall content suggests an elevated importance of the active response in determining overall vessel behavior. This study is a continuation of our previous investigation, in which a four-fiber constitutive model of the passive response of the primary porcine renal artery was identified. Here we focus on the active response of this vessel, specifically in the case of maximal SMC contraction, and develop a constitutive model of the active stress-stretch relations. The results of this study demonstrate the existence of biaxial active stress in the vessel wall, and suggest the active mechanical response is a critical component of renal arterial performance.

A STRUCTURE-MOTIVATED MODEL OF THE PASSIVE MECHANICAL RESPONSE OF THE PRIMARY PORCINE RENAL ARTERY

The primary renal arteries transport up to one fourth of cardiac output to the kidneys for blood plasma ultrafiltration, with a functional dependence on the vessel geometry, composition and mechanical properties. Despite the critical physiological function of the renal artery, the few biomechanical studies that have focused on this vessel are either uniaxial or only partially describe its bi-axial mechanical behavior. In this study, we quantify the passive mechanical response of the primary porcine renal artery through bi-axial mechanical testing that probes the pressure-deformed diameter and pressure-axial force relationships at various longitudinal extensions, including the in-vivo axial stretch ratio. Mechanical data are used to parameterize and validate a structure-motivated constitutive model of the arterial wall. Together, experimental data and theoretical predictions of the stress distribution within the arterial wall provide a comprehensive description of the passive mechanical response of the porcine renal artery.

The perivascular environment along the vertebral artery governs segment-specific structural and mechanical properties.

The vertebral arteries (VAs) are anatomically divided into four segments (V1-V4), which cumulatively transport blood flow through neck and ultimately form the posterior circulation of the brain. The vital physiological function of these conduit vessels depends on their geometry, composition and mechanical properties, all of which may vary among the defined arterial segments. Despite their significant role in blood circulation and susceptibility to injury, few studies have focused on characterizing the mechanical properties of VAs, and none have investigated the potential for segmental variation that could arise due to distinct perivascular environments. In this study, we compare the passive mechanical response of the central, juxtaposed arterial segments of porcine VAs (V2 and V3) via inflation-extension mechanical testing. Obtained experimental data and histological measures of arterial wall composition were used to adjust parameters of structure-motivated constitutive models that quantify the passive mechanical properties of each arterial segment and enable prediction of wall stress distributions under physiologic loads and boundary conditions. Our findings reveal significant segmental differences in the arterial wall geometry and structure. Nevertheless, similar wall stress distributions are predicted in these neighboring arterial segments if calculations account for their specific perivascular environments. These findings allow speculation that segmental differences in wall structure and geometry are a consequence of a previously introduced principle of optimal operation of arteries, which ensures effective bearing of physiological load and a favorable mechanical environment for mechanosensitive vascular smooth muscle cells. STATEMENT OF SIGNIFICANCE Among the numerous biomechanical investigations devoted to conduit blood vessels, only a few deal with vertebral arteries. While these studies provide useful information that describes the vessel mechanical response, they do not enable identification of a constitutive formulation of the mechanical properties of the vessel wall. This is an important distinction, as a constitutive material model is required to calculate the local stress environment of mechanosensitive vascular cells and fully understand the mechanical implications of both vascular injury and clinical intervention. Moreover, segmental differences in the mechanical properties of the vertebral arteries could be used to discriminate among distinct modes of injury and disease etiologies.

Active Stress in the Porcine Renal Artery

As a typical muscular conduit artery, the renal artery manifests an active response when the vascular smooth muscle is stimulated to contract. To present there are few experimental data [1] and no constitutive formulation of the renal arterial tissue that accounts for the active stress developed when the smooth muscle cells (SMCs) are stimulated to contract. Most studies identify the circumferential and axial active stresses by processing the in-vitro experimentally recorded change in diameter and axial force in a tubular arterial specimen inflated by an internal pressure, kept at constant axial stretch ratio, and with the SMCs stimulated to relax or contract. It is assumed that the stress borne by the extracellular matrix, termed as passive stress, and the active stress generated by the stimulated SMCs are additive. The directions of the active stresses and functional dependence on the strain measures are often postulated on the basis of histology, biophysics of SMC contraction, and an a priori guess, rather than on recordable mechanical information. The only exception is a recently proposed approach that allows decoupling of the passive and active response and identifying the arguments and the analytical form of the active stress directly from experimental data [2]. In this study, we follow this approach and determine the active stress in the porcine renal artery.Copyright

Using Digital Image Correlation to Characterize Local Strains on Vascular Tissue Specimens.

Characterization of the mechanical behavior of biological and engineered soft tissues is a central component of fundamental biomedical research and product development. Stress-strain relationships are typically obtained from mechanical testing data to enable comparative assessment among samples and in some cases identification of constitutive mechanical properties. However, errors may be introduced through the use of average strain measures, as significant heterogeneity in the strain field may result from geometrical non-uniformity of the sample and stress concentrations induced by mounting/gripping of soft tissues within the test system. When strain field heterogeneity is significant, accurate assessment of the sample mechanical response requires measurement of local strains. This study demonstrates a novel biomechanical testing protocol for calculating local surface strains using a mechanical testing device coupled with a high resolution camera and a digital image correlation technique. A series of sample surface images are acquired and then analyzed to quantify the local surface strain of a vascular tissue specimen subjected to ramped uniaxial loading. This approach can improve accuracy in experimental vascular biomechanics and has potential for broader use among other native soft tissues, engineered soft tissues, and soft hydrogel/polymeric materials. In the video, we demonstrate how to set up the system components and perform a complete experiment on native vascular tissue.

Mechanical Response of Tissue Constructs Fabricated From Self-Adhering Cellularized Microcarriers

Understanding how soft tissues behave in response to mechanical loading is essential in the field of biomechanics. Therefore, when a new tissue construct is fabricated, it is necessary to characterize its mechanical response using an appropriate test to quantify the material properties while minimizing error and artifact. To fully understand the behavior of the tissue construct, one should then be able to describe the behavior using a mechanical model.Copyright