Microtubules and morphogenesis in ordinary epidermal cells ofVigna sinensis leaves

Summary Undifferentiated ordinary epidermal cells (ECs) ofVigna sinensis leaves possess straight anticlinal walls and cortical microtubules (Mts) scattered along them. At an early stage of EC differentiation cortical Mts adjacent to the above walls form bundles normal to the leaf plane, loosely interconnected through the cortical cytoplasm of the internal periclinal wall. At the upper ends of the Mt bundles, Mts fan out towards the external periclinal wall and form radial arrays. Mt bundles and radial arrays exhibit strict alternate disposition between neighbouring ECs. An identical reticulum of cellulose microfibril (CM) bundles is deposited outside the Mt bundles. Local wall pads rise at the junctions of anticlinal walls with the external periclinal one, where the CM bundles terminate. They display radial CMs fanning towards the external periclinal wall. The CM bundles and radial CM systems prevent local cell bulging, but allow it in the intervening wall areas. In particular, the radial CM systems dictate the pattern of EC waviness by favouring local tangential expansion of external periclinal wall. As a result, ECs obtain an undulate appearance. Constrictions in one EC correspond with protrusions of adjacent ECs. ECs affected by colchicine entirely lose their Mts and do not develop wavy walls, an observation substantiating the role of cortical Mts in EC morphogenesis.Abbreviations CM cellulose microfibril - DTT dithiothreitol - EC epidermal cell - MSB microtubule stabilizing buffer - Mt microtubule - PBS phosphate buffered saline - PMSF phenylmethylsulfonyl fluoride     

Endothelialized biomaterials for tissue engineering applications in vivo

Rebuilding tissues involves the creation of a vasculature to supply nutrients and this in turn means that the endothelial cells (ECs) of the resulting endothelium must be a quiescent non-thrombogenic blood contacting surface. Such ECs are deployed on biomaterials that are composed of natural materials such as extracellular matrix proteins or synthetic polymers in the form of vascular grafts or tissue-engineered constructs. Because EC function is influenced by their origin, biomaterial surface chemistry and hemodynamics, these issues must be considered to optimize implant performance. In this review, we examine the recent in vivo use of endothelialized biomaterials and discuss the fundamental issues that must be considered when engineering functional vasculature.     

Vascular dysfunction in aged mice contributes to persistent lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease thought to result from impaired lung repair following injury and is strongly associated with aging. While vascular alterations have been associated with IPF previously, the contribution of lung vasculature during injury resolution and fibrosis is not well understood. To compare the role of endothelial cells (ECs) in resolving and non‐resolving models of lung fibrosis, we applied bleomycin intratracheally to young and aged mice. We found that injury in aged mice elicited capillary rarefaction, while injury in young mice resulted in increased capillary density. ECs from the lungs of injured aged mice relative to young mice demonstrated elevated pro‐fibrotic and reduced vascular homeostasis gene expression. Among the latter, Nos3 (encoding the enzyme endothelial nitric oxide synthase, eNOS) was transiently upregulated in lung ECs from young but not aged mice following injury. Young mice deficient in eNOS recapitulated the non‐resolving lung fibrosis observed in aged animals following injury, suggesting that eNOS directly participates in lung fibrosis resolution. Activation of the NO receptor soluble guanylate cyclase in human lung fibroblasts reduced TGFβ‐induced pro‐fibrotic gene and protein expression. Additionally, loss of eNOS in human lung ECs reduced the suppression of TGFβ‐induced lung fibroblast activation in 2D and 3D co‐cultures. Altogether, our results demonstrate that persistent lung fibrosis in aged mice is accompanied by capillary rarefaction, loss of EC identity, and impaired eNOS expression. Targeting vascular function may thus be critical to promote lung repair and fibrosis resolution in aging and IPF.     

Genistein‐3′‐sodium sulphonate protects against lipopolysaccharide‐induced lung vascular endothelial cell apoptosis and acute lung injury via BCL‐2 signalling

Under septic conditions, Lipopolysaccharide (LPS)‐induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein‐3′‐sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro‐protective effects through its anti‐apoptotic property. However, whether GSS protects against sepsis‐induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS‐induced Myd88/NF‐κB/BCL‐2 signalling pathway activation and subsequent EC apoptosis were effectively down‐regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis‐induced BCL‐2 changes in expression in mouse lungs but also blocked sepsis‐associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis‐induced ALI via its regulating effects on Myd88/NF‐κB/BCL‐2 signalling in lung ECs.     

Three-dimensional growth of endothelial cells in the microgravity-based rotating wall vessel bioreactor

We characterized bovine aortic endothelial cells (BAEC) continuously cultured in the rotating wall vessel (RWV) bioreactor for up to 30 d. Cultures grew as large tissue-like aggregates (containing 20 or more beads) after 30 d. These cultures appeared to be growing in multilayers around the aggregates, where single beads were covered with confluent BAEC, which displayed the typical endothelial cell (EC) morphology. The 30-d multibead aggregate cultures have a different and smoother surface when viewed under a higher-magnification scanning electron microscope. Transmission electron microscopy of these large BAEC aggregates showed that the cells were viable and formed multilayered sheets that were separated by an extracellular space containing matrix-like material. These three-dimensional cultures also were found to have a basal production of nitric oxide (NO) that was 10-fold higher for the RWV than for the Spinner flask bioreactor (SFB). The BAEC in the RWV showed increased basal NO production, which was dependent on the RWV rotation rate: 73% increase at 8 rpm, 262% increase at 15 rpm, and 500% increase at 20 rpm as compared with control SFB cultures. The addition of l-arginine to the RWV cultures resulted in a fourfold increase in NO production over untreated RWV cultures, which was completely blocked by L-NAME [N(G)-nitro-L-arginine-methylester]. Cells in the SFB responded similarly. The RWV cultures showed an increase in barrier properties with an up-regulation of tight junction protein expression. We believe that this study is the first report of a unique growth pattern for ECs, resulting in enhanced NO production and barrier properties, and it suggests that RWV provides a unique model for investigating EC biology and differentiated function.     

Fibrinogen induces adhesion, spreading, and microfilament organization of human endothelial cells in vitro

Human umbilical vein endothelial cells (ECs) have been shown to attach to a substratum of fibrinogen (fg). Later, ECs undergo spreading, organization of thick microfilament bundles of the stress fiber type, and formation of focal contacts (adhesion plaques) that correspond to accumulation of vinculin at the cytoplasmic aspect of the ventral membrane. The rate of attachment to fg and the type of spreading is virtually identical to that obtained on substrata coated with fibronectin (FN). Antibodies to fg, but not to FN, prevent EC adhesion to fg; conversely, antibodies to FN, but not to fg, prevent adhesion of ECs to a FN-coated substratum. The removal of residual FN contamination from fg preparations by means of DEAE-cellulose chromatography does not result in any difference in EC adhesion on fg. Moreover, pretreatment of cells with inhibitors of synthesis and release of proteins does not impair their adhesion capacity on an fg-coated substratum. In contrast, human arterial smooth muscle cells do not adhere and spread on fg substrata but do so on FN. The synthetic peptides (Gly-Arg-Gly-Asp[GRGD] and Gly-Arg-Gly-Asp-Ser-Pro[GRGDSP]) containing the tripeptide Arg-Gly-Asp (RGD), originally found to be responsible for the cell binding activity of FN, have been found to inhibit EC spreading and the redistribution of their cytoskeleton, including the formation of stress fibers and the localization of vinculin either on fg or on FN. Conversely, the synthetic peptide Arg-Gly-Gly (RGG) was completely uneffective in inhibiting the adhesion and the sequence of events leading to spreading and cytoskeletal organization. These results indicate that ECs, but not smooth muscle cells, specifically adhere and spread on an fg substratum and this occurs by recognition mechanisms similar to those reported for FN.     

Characterizing mixing in a rotating drum bioreactor for solid-state fermentation

A method, based on the use of wheat bran particles dyed with Rhodamine-WT as tracer particles, was developed to characterize mixing in a 200 l rotating drum bioreactor used for solid state fermentation. The extraction process contributes a 15% relative error in determining Rhodamine concentrations. Extraction efficiency is not affected by autoclaving of the bran and there is no inter-particle transfer of dye during the mixing of bran within the drum. For an unbaffled drum rotated at 5 rpm the axial dispersion coefficient is 9.15 cm² min^–1.     

Laminar shear stress elicit distinct endothelial cell e‐selectin expression pattern via TNFα and IL‐1β activation

The ability to discriminate cell adhesion molecule expression between healthy and inflamed endothelium is critical for therapeutic intervention in many diseases. This study explores the effect of laminar flow on TNFα‐induced E‐selectin surface expression levels in human umbilical vein endothelial cells (HUVECs) relative to IL‐1β‐induced expression via flow chamber assays. HUVECs grown in static culture were either directly (naïve) activated with cytokine in the presence of laminar shear or pre‐exposed to 12 h of laminar shear (shear‐conditioned) prior to simultaneous shear and cytokine activation. Naïve cells activated with cytokine in static served as control. Depending on the cell shear history, fluid shear is found to differently affect TNFα‐induced relative to IL‐1β‐induced HUVEC expression of E‐selectin. Specifically, E‐selectin surface expression by naïve HUVECs is enhanced in the 8–12 h activation time range with simultaneous exposure to shear and TNFα (shear‐TNFα) relative to TNFα static control whereas enhanced E‐selectin expression is observed in the 4–24 h range for shear‐IL‐1β treatment relative to IL‐1β static control. While exposure of HUVECs to shear preconditioning mutes shear‐TNFα‐induced E‐selectin expression, it enhances or down‐regulates shear‐IL‐1β‐induced expression dependent on the activation period. Under dual‐cytokine‐shear conditions, IL‐1β signaling dominates. Overall, a better understanding of E‐selectin expression pattern by human ECs relative to the combined interaction of cytokines, shear profile and history can help elucidate many disease pathologies. Biotechnol. Bioeng. 2013; 110: 999–1003. © 2012 Wiley Periodicals, Inc.     

PRC1‐labeled microtubule bundles and kinetochore pairs show one‐to‐one association in metaphase

In the mitotic spindle, kinetochore microtubules form k‐fibers, whereas overlap or interpolar microtubules form antiparallel arrays containing the cross‐linker protein regulator of cytokinesis 1 (PRC1). We have recently shown that an overlap bundle, termed bridging fiber, links outermost sister k‐fibers. However, the relationship between overlap bundles and k‐fibers throughout the spindle remained unknown. Here, we show that in a metaphase spindle more than 90% of overlap bundles act as a bridge between sister k‐fibers. We found that the number of PRC1‐GFP‐labeled bundles per spindle is nearly the same as the number of kinetochore pairs. Live‐cell imaging revealed that kinetochore movement in the equatorial plane of the spindle is highly correlated with the movement of the coupled PRC1‐GFP‐labeled fiber, whereas the correlation with other fibers decreases with increasing distance. Analysis of endogenous PRC1 localization confirmed the results obtained with PRC1‐GFP. PRC1 knockdown reduced the bridging fiber thickness and interkinetochore distance throughout the spindle, suggesting a function of PRC1 in bridging microtubule organization and force balance in the metaphase spindle.     

Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function

Pharmacological focal adhesion kinase (FAK) inhibition prevents tumor growth and metastasis, via actions on both tumor and stromal cells. In this paper, we show that vascular endothelial cadherin (VEC) tyrosine (Y) 658 is a target of FAK in tumor-associated endothelial cells (ECs). Conditional kinase-dead FAK knockin within ECs inhibited recombinant vascular endothelial growth factor (VEGF-A) and tumor-induced VEC-Y658 phosphorylation in vivo. Adherence of VEGF-expressing tumor cells to ECs triggered FAK-dependent VEC-Y658 phosphorylation. Both FAK inhibition and VEC-Y658F mutation within ECs prevented VEGF-initiated paracellular permeability and tumor cell transmigration across EC barriers. In mice, EC FAK inhibition prevented VEGF-dependent tumor cell extravasation and melanoma dermal to lung metastasis without affecting primary tumor growth. As pharmacological c-Src or FAK inhibition prevents VEGF-stimulated c-Src and FAK translocation to EC adherens junctions, but FAK inhibition does not alter c-Src activation, our experiments identify EC FAK as a key intermediate between c-Src and the regulation of EC barrier function controlling tumor metastasis.     

Proteomic profiling of endothelial cells in human lung cancer

Genomic and proteomic analysis of normal and diseased tissues have yielded an abundance of molecular information for diagnostic and potential therapeutic targets. Changing the target of analysis from poorly accessible cells within tissues to easily accessible vascular endothelium has theoretical advantages in tissue-specific targeting. In this study, we sought to map a large-scale proteome of microvascular endothelium in human non-small cell lung cancer (NSCLC) and normal lung tissues, and identify lung cancer-related endothelial cell (EC)-selective proteins. Endothelial cells were isolated within NSCLC tissues and adjacent-normal lung tissue of lung cancer patients by using CD31-immunomagnetic beads. The complex proteins from the ECs were separated by one-dimensional gel electrophoresis, and the proteins in each gel band were digested by trypsin. Peptides were separated by online reverse-phase liquid-chromatography and analyzed by electrospray ionization (ESI) ion trap tandem mass spectrometry. Approximately 600-1000 proteins were identified in each individual sample. Five patient cases of paired individual data, extracted from the protein identification data sets of both normal- and cancer-derived ECs, were analyzed by subtractive proteomics. An average of 300 proteins was specifically identified from each lung cancer-derived EC isolate, compared to normal lung-derived ECs. With the use of several comparative analyses, we identified among those 300 proteins, 16 common candidate proteins that were detected in at least 3 of 5 cases specific to lung cancer-derived ECs. Proteins selectively identified in cancer-derived ECs, including coatomer protein complex, subunit gamma (COPG), and peroxiredoxin 4 (PRDX4), were validated by Western blot analysis. In an additional experiment in which 16 cancer samples were analyzed by immunohistochemistry, PRDX4, thymopoietin (TMPO), and COPG were confirmed to be abundantly expressed in lung cancer-derived ECs and in cancerous lung cells. Further ongoing analysis of these 16 candidate proteins will determine their potential applicability to NSCLC-specific diagnosis and therapeutics.     

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137‐modified ECs (CD137‐Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti‐CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137‐Exo efficiently induced the progression of AS in ApoE^?/? mice. CD137‐Exo increased the proportion of Th17 cells both in vitro and vivo. The IL‐6 contained in CD137‐Exo which is regulated by Akt and NF‐КB pathway was verified to activate Th17 cell differentiation. IL‐17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM‐1), monocyte chemoattractant protein‐1 (MCP‐1) and E‐selectin in the supernatants of ECs after IL‐17 treatment was dramatically increased. CD137‐Exo promoted the progression of AS and Th17 cell differentiation via NF‐КB pathway mediated IL‐6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS.     

High-purity isolation of bullfrog hair bundles and subcellular and topological localization of constituent proteins.

The small number of hair cells in auditory and vestibular organs severely impedes the biochemical characterization of the proteins involved in mechano-electrical transduction. By developing an efficient and clean "twist-off" method of hair bundle isolation, and by devising a sensitive, nonradioactive method to detect minute quantities of protein, we have partially overcome this limitation and have extensively classified the proteins of the bundles. To isolate hair bundles, we glue the saccular macula of the bullfrog to a glass coverslip, expose the tissue to a molten agarose solution, and allow the agarose to solidify to a firm gel. By rotating the gel disk with respect to the fixed macula, we isolate the hair bundles by shearing them at their mechanically weak bases. The plasma membranes of at least 80% of the stereocilia reseal. To visualize the proteins of the hair bundle, we covalently label them with biotin, separate them by SDS-PAGE, and transfer them to a charged nylon membrane. We can detect less than 500 fg of protein by probing the membrane with streptavidin-alkaline phosphatase and detecting the chemiluminescent product from the hydrolysis of the substrate 3-(4-methoxyspiro-(1,2-dioxetane-3,2'-tricyclo-[3.3.1. 1(3.7)]decan)-4-yl) phenyl phosphate (AMPPD). These techniques reveal a distinct constellation of proteins in and associated with hair bundles. Several proteins, such as calmodulin, calbindin, actin, tubulin, and fimbrin, have previously been described. A second class of proteins in the preparation appears to be derived from extracellular sources. Finally, several heretofore undescribed bundle proteins are identified and characterized by their membrane topology, subcellular localization, and glycosidase and protease sensitivities.     

Downregulation of tissue factor (TF) by RNA interference induces apoptosis and impairs cell survival of primary endothelium and tumor cells

Tissue factor (TF) has been implicated in the thrombotic complications seen during vascular rejection of allografts and may contribute to intimal hyperplasia in chronic allograft vasculopathy. Downregulation of endothelial TF expression post-transplantation could therefore be of therapeutic value. Lentivirus-mediated RNA interference was used in primary endothelial cells (EC) to investigate its effects on TF protein expression and functional activity. Lentivirus-mediated expression of a TF-specific short-interfering (si) RNA with green fluorescent protein as a reporter gene (siRNATF-GFP) resulted in a 42 +/- 3.9% reduction in EC surface-expressed TF as compared with cells expressing a scrambled siRNATF sequence (P = 0.025). The TF content in EC lysates was reduced from 6.85 +/- 1.99 ng to 3.05 +/- 0.82 ng (P = 0.006). Factor X (FX) activation was not impaired on the apical EC surface. The subendothelial matrix of ECs with low TF expression showed significantly reduced TF activity compared with non-transduced cells or with cells harboring the empty vector. ECs expressing siRNATF-GFP exhibited reduced reporter gene (GFP) expression and cell density and an altered morphology. Transfection of control cells with high (J82 cells) or low (MiaPaCa-2 cells) TF expression with siRNATF oligonucleotides caused apoptosis of the J82 but not of the MiaPaCa-2 cells. Thus, lentivirus-mediated RNA interference reduces the TF expression of activated ECs but does not affect FX activation by TF/FVIIa expressed on the apical surface. The downregulation has nevertheless substantial negative effects on the viability of ECs and TF-expressing control cells. These findings imply that certain levels of TF are required for the maintained viability and growth of endothelium and TF-expressing tumor cells.     

Coculture of Endothelial Cells with Human Pluripotent Stem Cell‐Derived Cardiac Progenitors Reveals a Differentiation Stage‐Specific Enhancement of Cardiomyocyte Maturation

Cardiomyocytes (CMs) generated from human pluripotent stem cells (hPSCs) are immature in their structure and function, limiting their potential in disease modeling, drug screening, and cardiac cellular therapies. Prior studies have demonstrated that coculture of hPSC‐derived CMs with other cardiac cell types, including endothelial cells (ECs), can accelerate CM maturation. To address whether the CM differentiation stage at which ECs are introduced affects CM maturation, the authors coculture hPSC‐derived ECs with hPSC‐derived cardiac progenitor cells (CPCs) and CMs and analyze the molecular and functional attributes of maturation. ECs have a more significant effect on acceleration of maturation when cocultured with CPCs than with CMs. EC coculture with CPCs increases CM size, expression of sarcomere, and ion channel genes and proteins, the presence of intracellular membranous extensions, and chronotropic response compared to monoculture. Maturation is accelerated with an increasing EC:CPC ratio. This study demonstrates that EC incorporation at the CPC stage of CM differentiation expedites CM maturation, leading to cells that may be better suited for in vitro and in vivo applications of hPSC‐derived CMs.     

Recruitment of knee joint ligaments

On the basis of earlier reported data on the in vitro kinematics of passive knee-joint motions of four knee specimens, the length changes of ligament fiber bundles were determined by using the points of insertion on the tibia and femur. The kinematic data and the insertions of the ligaments were obtained by using Roentgenstereophotogrammetry. Different fiber bundles of the anterior and posterior cruciate ligaments and the medial and lateral collateral ligaments were identified. On the basis of an assumption for the maximal strain of each ligament fiber bundle during the experiments, the minimal recruitment length and the probability of recruitment were defined and determined. The motions covered the range from extension to 95 degrees flexion and the loading conditions included internal or external moments of 3 Nm and anterior or posterior forces of 30 N. The ligament length and recruitment patterns were found to be consistent for some ligament bundles and less consistent for other ligament bundles. The most posterior bundle of each ligament was recruited in extension and the lower flexion angles, whereas the anterior bundle was recruited for the higher flexion angles. External rotation generally recruited the collateral ligaments, while internal rotation recruited the cruciate ligaments. However, the anterior bundle of the posterior cruciate ligament was recruited with external rotation at the higher flexion angles. At the lower flexion angles, the anterior cruciate and the lateral collateral ligaments were recruited with an anterior force. The recruitment of the posterior cruciate ligament with a posterior force showed that neither its most anterior nor its most posterior bundle was recruited at the lower flexion angles. Hence, the posterior restraint must have been provided by the intermediate fiber bundles, which were not considered in the experiment. At the higher flexion angles, the anterior bundles of the anterior cruciate ligament and the posterior cruciate ligament were found to be recruited with anterior and posterior forces, respectively. The minimal recruitment length and the recruitment probability of ligament fiber bundles are useful parameters for the evaluation of ligament length changes in those experiments where no other method can be used to determine the zero strain lengths, ligament strains and tensions.     

Analysis of the contraction of an organelle using its birefringency: the R-fibre of the Ceratium (Dinoflagellate) flagellum

Some organelles responsible for contraction consist of bundles of 2-4 nm filaments called nanofilaments. Such organelles are present in the longitudinal flagellum of Ceratium (Dinoflagellate): the R-fibre is the motor system for contraction and parallels the axoneme, which is responsible for wave generation. We used a highly sensitive polarization microscope developed by one of the authors to measure the birefringence of these nanofilament bundles during contraction in vivo. Our results show that the R-fibre gives a highly birefringent signal, retarding the polarization to much the same extent irrespective of the direction of polarization. By rotating the axis of the microscope compensator we confirmed that the birefringence is positive, suggesting that the bundles run parallel to the longitudinal axis of the flagellum. Conversely, when the compensator was rotated contrary to the direction of retardation, the bundle appeared dark (except when the organelle was in a fully contracted state). Experiments performed on detergent-treated and ATP-reactivated flagella show that a portion of the flagella regained activity with the addition of ATP in the presence of low Ca(2+) concentrations. This demonstrates the ability to reactivate flagellar motility after permeabilization and that axonemal microtubules were not responsible for the strong flagellar birefringence. Combined with complementary data from DIC microscopy of demembranated flagella and electron microscopy, these findings have led to the development of a model of the R-fibre and a comparison with other types of birefringent nanofilament bundles, such as the myoneme of Acantharia.     

Growth responses of barley seedling to simulated weightlessness induced by two-axis rotation

Summary A device used for simulated weightless studies is described and is called the Nogravatron. The Nogravatron apparatus produces simulated weight-lessness by rotating seedlings simultaneously at the rate of 0.25 rpm and 1.0 rpm in two axes perpendicular to each other. Atlas barley seedlings grown on the apparatus grew at rates different from that of stationary controls. Coleoptile elongation in rotated barley was not inhibited by light during the first 55 hours of rotation treatment whereas stationary controls were photoinhibited. After 55 hours the growth of rotated coleoptiles was inhibited by light. The coleoptiles did not show movements and were oriented along the longitudinal axis of the seed. Roots also did not show geotropic movements but the growth direction was affected by the proximity of other roots. Coleoptiles rotated in dark were significantly longer than stationary controls on the third and fourth day but not so on the fifth day and later. Coleoptiles rotated in light were about 35 percent longer than the stationary coleoptiles by the third day and maintained this significant difference to the end of the experiment.Supported in part by NASA Grant NsG 538-63 and by Air Force Office of Scientific Research Office of Aerospace Research, United States Air Force, Contract No. AF 49 (638)-1387.     

Pulsatile flow and mass transport over an array of cylinders: gas transfer in a cardiac-driven artificial lung

The pulsatile flow and gas transport of a Newtonian passive fluid across an array of cylindrical microfibers are numerically investigated. It is related to an implantable, artificial lung where the blood flow is driven by the right heart. The fibers are modeled as either squared or staggered arrays. The pulsatile flow inputs considered in this study are a steady flow with a sinusoidal perturbation and a cardiac flow. The aims of this study are twofold: identifying favorable array geometry/spacing and system conditions that enhance gas transport; and providing pressure drop data that indicate the degree of flow resistance or the demand on the right heart in driving the flow through the fiber bundle. The results show that pulsatile flow improves the gas transfer to the fluid compared to steady flow. The degree of enhancement is found to be significant when the oscillation frequency is large, when the void fraction of the fiber bundle is decreased, and when the Reynolds number is increased; the use of a cardiac flow input can also improve gas transfer. In terms of array geometry, the staggered array gives both a better gas transfer per fiber (for relatively large void fraction) and a smaller pressure drop (for all cases). For most cases shown, an increase in gas transfer is accompanied by a higher pressure drop required to power the flow through the device.