Vascular response to the microcirculation in the fingertip by local vibration with varied amplitude.

Objectives: We investigated the effect of local vibration intensity on the vascular response to the microcirculation of the finger. Materials and methods: We performed hand-transmitted vibration experiments combined with laser Doppler flowmetry (LDF) to measure the blood perfusion signals of fingertips in the vibrated hand and the contralateral middle finger under the same frequency and different amplitude vibration, and to analyze the changes of microcirculatory blood perfusion levels in the fingers, and to investigate the effects of vibration stimulation on the endothelial, neural and myogenic regulatory frequency ranges of fingertips based on wavelet analysis. Furthermore, the transparent silicone films were fabricated and cultured with vascular endothelial cell (EC), which will undergo the local vibration with varied amplitude. And the expression of inflammatory factors was detected in the ECs. Results: Low-frequency vibration leads to a decreased blood flow in fingertip, and the degree of reduction in fingertip blood flow increases as the amplitude gradually increases, and the period required for blood flow to return to normal level after hand-transmitted vibration gradually increases. The decrease in blood flow is more pronounced in the vibrating hand than in the contralateral hand. In addition, nuclear factor-κB (NF-κB) expression increased significantly with the increase of vibration amplitude. Conclusion: High amplitude vibrations caused the inflammatory reaction of ECs which will lead to the altered endothelial regulatory activity. The endothelial regulatory activity is closely related to the blood perfusion in the microcirculation.

Experimental Study of the Propagation Process of Dissection Using an Aortic Silicone Phantom.

BACKGROUND: The mortality of acute aortic dissection (AD) can reach 65~70%. However, it is challenging to follow the progress of AD formation. The purpose of this work was to observe the process of dissection development using a novel tear-embedded silicone phantom. METHODS: Silicone phantoms were fabricated by embedding a torn area and primary tear feature on the inner layer. CT scanning and laser lightening were conducted to observe the variations in thickness and volume of the true lumen (TL) and false lumen (FL) during development. RESULTS: The model with a larger interlayer adhesion damage required a lower pressure to trigger the development of dissection. At the initiation stage of dissection, the volume of TL increased by 25.5%, accompanied by a 19.5% enlargement of tear size. The force analysis based on the change of tear size verified the deduction of the process of interlaminar separation from the earlier studies. CONCLUSIONS: The primary tear and the weakening adhesion of the vessel layers are key factors in AD development, suggesting that some forms of primary damage to the arterial wall, in particular, the lumen morphology of vessels with straight inner lumen, should be considered as early risk predictors of AD.

Lingering Dynamics of Type 2 Diabetes Mellitus Red Blood Cells in Retinal Arteriolar Bifurcations.

It has been proven that the deformability of red blood cells (RBC) is reduced owing to changes in mechanical properties, such as diabetes mellitus and hypertension. To probe the effects of RBC morphological and physical parameters on the flow field in bifurcated arterioles, three types of RBC models with various degrees of biconcave shapes were built based on the in vitro experimental data. The dynamic behaviors of the RBCs in shear flow were simulated to validate the feasibility of the finite element-Arbitrary Lagrangian-Eulerian method with a moving mesh. The influences of the shear rate and viscosity ratios on RBC motions were investigated. The motion of RBCs in arteriolar bifurcations was further simulated. Abnormal variations in the morphological and physical parameters of RBCs may lead to diminished tank-tread motion and enhanced tumbling motion in shear flow. Moreover, abnormal RBC variations can result in slower RBC motion at the bifurcation with a longer transmit time and greater flow resistance, which may further cause inadequate local oxygen supply. These findings would provide useful insights into the microvascular complications in diabetes mellitus.

In Vitro Study of Endothelial Cell Morphology and Gene Expression in Response to Wall Shear Stress Induced by Arterial Stenosis.

Objectives: We examined the correlation between changes in hemodynamic characteristics induced by arterial stenosis and vascular endothelial cell (EC) morphology and gene expression in straight silicone arteries. Materials and methods: Transparent silicone straight artery models with four degrees of stenosis (0, 30, 50, and 70%) were fabricated. Particle image velocimetry was performed to screen silicone vessel structures with good symmetry and to match the numerical simulations. After the inner surface of a symmetric model was populated with ECs, it was perfusion-cultured at a steady flow rate. A computational fluid dynamics (CFD) study was conducted under the same perfusion conditions as in the flow experiment. The high-WSS region was then identified by CFD simulation. EC morphology in the high-WSS regions was characterized by confocal microscopy. ECs were antibody-stained to analyze the expression of inflammatory factors, including matrix metalloproteinase (MMP)-9 and nuclear factor (NF)-κB, which were then correlated with the CFD simulations. Results: As the degree of vascular stenosis increases, more evident jet flow occurs, and the maximum WSS position moves away first and then back. ECs were irregularly shaped at vortex flow regions. The number of gaps between the cells in high-WSS regions increased. The MMP-9 and NF-κB expression did not differ between vessels with 30 and 0% stenosis. When arterial stenosis was 70%, the MMP-9 and NF-κB expression increased significantly, which correlated with the regions of substantially high WSS in the CFD simulations. Conclusion: Stenotic arteries induce hemodynamic stress variations, which contribute to differences in EC morphology and gene expression. A high degree of vascular stenosis can directly increase inflammatory factor expression.

A Versatile and Robust Platform for the Scalable Manufacture of Biomimetic Nanovaccines.

Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen-presenting source exemplifies, such as a promising strategy. For translation, a standardizable, consistent, and scalable approach for coating nanoadjuvant with the cell membrane is important. Here a turbulent mixing and self-assembly method called flash nanocomplexation (FNC) for producing cell membrane-coated nanovaccines in a scalable manner is demonstrated. The broad applicability of this FNC technique compared with bulk-sonication by using ten different core materials and multiple cell membrane types is shown. FNC-produced biomimetic nanoparticles have promising colloidal stability and narrow particle polydispersity, indicating an equal or more homogeneous coating compared to the bulk-sonication method. The potency of a nanovaccine comprised of B16-F10 cancer cell membrane decorating mesoporous silica nanoparticles loaded with the adjuvant CpG is then demonstrated. The FNC-fabricated nanovaccines when combined with anti-CTLA-4 show potency in lymph node targeting, DC antigen presentation, and T cell immune activation, leading to prophylactic and therapeutic efficacy in a melanoma mouse model. This study advances the design of a biomimetic nanovaccine enabled by a robust and versatile nanomanufacturing technique.

Synchronized research on endothelial dysfunction and microcirculation structure in dorsal skin of rats with type 2 diabetes mellitus.

The aim of this study was to explore changes in the microvascular tone as measured by laser Doppler flowmetry (LDF) and the microcirculation structure of the dorsal skin of rats with type 2 diabetes mellitus. The diabetic rat model was induced by a diet of high-sugar and high-lipid fodder combined with the injection of streptozotocin into the abdominal cavity. Depending on the interval between the development of diabetes and the experiments, the diabetic rats were subdivided into three groups. The evaluation of microvascular tone was based on the amplitude responses of the LDF signal fluctuations in the appropriate frequency range in the dorsal skin of the rats during a thermal test (at 42 °C). The nitric oxide (NO) level in plasma was also used as a marker of endothelial dysfunction. Changes in the microcirculation structure in the diabetic rats were estimated by measuring the microvascular density in the choke vessels of the dorsal skin of the rats. The experimental results with respect to red blood cell (RBC)-related parameters showed decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in three diabetic rats. The increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test and this was accompanied by abnormal NO levels in plasma of the diabetic groups as compared with healthy rats. A significant reduction in the microvascular density of the choke vessels of the dorsal skin was found only in the diabetic group at the most advanced stage of diabetes in this experiment. Thus, we suggest that endothelial dysfunction occurs in diabetic rats and changes in the microcirculation structure of the dorsal skin occur in a later stage of diabetes development. A. Photograph of measurement method by using a LDF probe and heating device in the dorsal skin of the rat. B. Dorsal skin LDF signals of a healthy rat during the thermal stimuli test. (a) Blood flow signal record for the test. Wavelet filtration of blood flow signal in (b) myogenic range, (c) neurogenic range, and (d) endothelial range.

Thermal Analysis of Blood Flow Alterations in Human Hand and Foot Based on Vascular-Porous Media Model.

Microvascular and Macrovascular diseases are serious complications of diabetic mellitus, which significantly affect the life quality of diabetic patients. Quantitative description of the relationship between temperature and blood flow is considerably important for non-invasive detection of blood vessel structural and functional lesions. In this study, thermal analysis has been employed to predict blood flow alterations in a foot and a cubic skin model successively by using a discrete vessel-porous media model and further compared the blood flows in 31 diabetic patients. The tissue is regarded as porous media whose liquid phase represents the blood flow in capillaries and solid phase refers to the tissue part. Discrete vascular segments composed of arteries, arterioles, veins, and venules were embedded in the foot model. In the foot thermal analysis, the temperature distributions with different inlet vascular stenosis were simulated. The local temperature area sensitive to the reduction of perfusion was obtained under different inlet blood flow conditions. The discrete vascular-porous media model was further applied in the assessment of the skin blood flow by coupling the measured skin temperatures of diabetic patients and an inverse method. In comparison with the estimated blood flows among the diabetic patients, delayed blood flow regulation was found in some of diabetic patients, implying that there may be some vascular disorders in these patients. The conclusion confirms the one in our previous experiment on diabetic rats. Most of the patients predicted to be with vascular disorders were diagnosed as vascular complication in clinical settings as well, suggesting the potential applications of the vascular-porous media model in health management of diabetic patients.

A Brush-Spin-Coating Method for Fabricating In Vitro Patient-Specific Vascular Models by Coupling 3D-Printing.

PURPOSE: In vitro patient-specific flexible vascular models are helpful for understanding the haemodynamic changes before and after endovascular treatment and for effective training of neuroendovascular interventionalists. However, it is difficult to fabricate models of overall unified or controllable thickness using existing manufacturing methods. In this study, we developed an improved and easily implemented method by combining 3D printing and brush-spin-coating processes to produce a transparent silicone model of uniform or varied thickness. METHODS: First, a water-soluble inner-skeleton model, based on clinical data, was printed on a 3D printer. The skeleton model was subsequently fixed in a single-axis-rotation machine to enable continuous coating of silicone, the thickness of which was manually controlled by adsorption and removal of excess silicone in a brush-spinning operation. After the silicone layer was solidified, the inner skeleton was further dissolved in a hot water bath, affording a transparent vascular model with real geometry. To verify the controllability of the coating thickness by using this method, a straight tube, an idealised aneurysm model, a patient-specific aortic arch model, and an abdominal aortic aneurysm model were manufactured. RESULTS: The different thicknesses of the manufactured tubes could be well controlled, with the relative standard deviations being 5.6 and 8.1% for the straight and aneurysm tubes, respectively. Despite of the diameter changing from 33 to 20 mm in the patient-specific aorta, the thickness of the fabricated aortic model remains almost the same along the longitudinal direction with a lower standard deviation of 3.1%. In the more complex patient-specific abdominal aneurysm model, varied thicknesses were realized to mimic the measured data from the CT images, where the middle of the aneurysm was with 2 mm and abdominal aorta as well as the iliac arteries had the normal thickness of 2.3 mm. CONCLUSION: Through the brush-spin-coating method, models of different sizes and complexity with prescribed thickness can be manufactured, which will be helpful for developing surgical treatment strategies or training neuroendovascular interventionalists.

Heat transfer analysis of blood perfusion in diabetic rats using a genetic algorithm.

Diabetes is frequently associated with structural and functional impairment of the microcirculation. Blood perfusion is an important indicator of both physiological and pathological conditions of the microcirculation. Given that temperature is closely related to blood perfusion and is more easily measured, blood perfusion can be estimated from variations in skin temperature using an inverse method. The aim of this paper was to develop a thermal analysis method for estimation of blood perfusion and apply it in the assessment of skin blood perfusion in diabetic rats. First, diabetes was induced in the rat models of the experimental group. Skin temperature from the rats left hind paws was measured during a 10-min local heating period followed by a 15-min cooling period. A simple one-dimensional heat transfer model, including an arteriolar vessel node, was used to describe the skin heat transfer process. The blood perfusion of the arteriole was estimated by correlating the calculated skin temperature with known experimental temperatures using a genetic algorithm. The results indicated that the average blood perfusion in the control group was higher during local heating and decreased faster during the cooling period, showing dynamic responses to the thermal stimuli. In contrast, the blood perfusion of diabetic rats was reduced compared with that of the control rats during the heating phase and the rate of decrease in perfusion during the cooling stage was similarly reduced, implying a slower response to thermal stimulation in these rats. It is interesting to note that diabetic rats fed a normal diet showed a similar blood perfusion pattern to that in the control rats, implying that diet may be important in the treatment of diabetes-associated microvascular dysfunction.

Enhancement of Meniscus Pump by Multiple Particles.

We numerically investigate the behavior of a droplet spreading on a smooth substrate with multiple obstacles. As experimental works have indicated, the macroscopic contact line or the three-phase boundary line of a droplet exhibits significant deformation resulting in a local acceleration by successive interactions with an array of tiny obstacles settled on the substrate (Mu et al., Langmuir 2019, 35). We focus on the menisci formation and the resultant pressure and velocity fields inside a liquid film in a two-spherical-particle system to realize an optimal design for the effective liquid-transport phenomenon. Special attention is paid to the meniscus formation around the second particle, which influences the liquid supply related to the pressure difference around the first particle as a function of the distance between the two particles. We find that the meniscus around the first particle plays an additional role as the reservoir of the liquid supplied toward the second particle, which is found to enhance the total pumping effect.

Pumping effect of heterogeneous meniscus formed around spherical particle.

HYPOTHESIS: A disturbance such as a microparticle on the pathway of a spreading droplet has shown the tremendous ability to accelerate locally the motion of the macroscopic contact line (Mu et al., 2017). Although this ability has been linked to the particle-liquid interaction, the physical mechanisms behind it are still poorly understood despite its academic interest and the scope of numerous industrial applications in need of fast wetting. EXPERIMENTS: In order to better understand the mechanisms behind the particle-liquid interaction, we numerically investigate the pressure and velocity fields in the liquid film. The results are compared to experiments assessing the temporal shape variation of the liquid-film meniscus from which pressure difference around the particle is evaluated. FINDINGS: The particle-induced acceleration of the film front depends both on the shape of the meniscus that forms around the particle foot and the liquid "reservoir" in the film that can be pumped thanks to the presence of the particle. The study validates the presence of three stages of pressure difference between the upstream and downstream regions of the meniscus around the particle, which leads to the local acceleration/deceleration of the macroscopic contact line. We indicate that asymmetric meniscus around the particle foot produces a net pressure force driving liquid and accelerating the liquid-film front.

Quick Liquid Propagation on a Linear Array of Micropillars.

The wetting process of a high energy surface can be accelerated locally through the capillary interaction of a liquid advancing front with a micro-object introduced to the surface (Mu et al., J. Fluid Mech, 2017, 830, R1). We demonstrate that a linear array of micropillars embedded in a fully wettable substrate can produce quick propagation of liquid along the array. It is observed that multiple interactions of a liquid front with pillars can induce the motion of liquid a hundred times faster than in the absence of pillars.

Computational analysis of nitric oxide biotransport in a microvessel influenced by red blood cells.

It is pivotal that endothelium-dependent Nitric Oxide (NO) consumed by hemoglobin (Hb) inside red blood cells (RBCs) membrane, regulates the vascular tone. The whole processes of NO transport in vessel containing flowing RBCs is still not clear, such as NO production in endothelium, diffusion in plasma and consumption inside RBCs. In this work, the motion of RBCs in a microvessel is investigated by using immersed boundary lattice Boltzmann method (IB-LBM) first and the deformability of RBCs is expressed by using spring network model which is based on the minimum energy principle. Furthermore, the interaction between RBCs is considered. Based on the wall shear stress (WSS), NO production rate originated from endothelium was obtained by using a hyperbolic model. NO distribution inside the microvessel with multiple RBCs was computed by using immersed boundary finite difference method (IB-FDM). The result shows that a large (small) WSS exists at locations with a relatively wide(narrow) gap between the wall and cell. In terms of mass transfer, an increase of RBC membrane permeability leads to a decrease of NO concentration in the vessel and the surrounding endothelium significantly. In addition, with the increasing of hematocrit (Hct) value, NO concentration distribution in the whole vessel decreases both in the lumen and vascular wall. Finally, the thickness of RBCs-depleted layer gradually decreases with the weakened deformability of RBCs membrane, and the change degree of cell free layer (CFL) thickness decreases as the bending stiffness is relatively higher. Thus, when bending stiffness is higher, the NO concentration in vascular wall is reduced resulting from the thinner CFL.

Numerical analysis of wall shear stress in ascending aorta before tearing in type A aortic dissection.

Although the incidence of many cardiovascular diseases has declined as medical treatments have improved, the prevalence of aortic dissection (AD) has increased. Compared to type B dissections, type A dissections are more severe, and most patients with type A dissections require surgical treatment. The objective of this study was to investigate the relationships between the wall shear stress (WSS) on the aortic endothelium and the frequent tearing positions using computational fluid dynamics. Five type A dissection cases and two normal aortas were included in the study. First, the structures of the aortas before the type A dissection were reconstructed on the basis of the original imaging data. Analyses of flow in the reconstructed premorbid structures reveals that the rupture positions in three of the five cases corresponded to the area of maximum elevated WSS. Moreover, the WSS at the junction of the aortic arch and descending aorta was found to be elevated, which is considered to be related to the locally disturbed helical flow. Meanwhile, the highest WSS in the patients with premorbid AD was found to be almost double that of the control group. Due to the noticeable morphological differences between the AD cases and the control group, the WSSs in the premorbid structures without vasodilation in the ascending part were estimated. The computational results revealed that the WSS was lower in the aorta without vasodilation, but the pressure drop in this situation was higher than that with vasodilation in the ascending aorta. Significant differences were seen between the AD cases and the control group in the angles of the side branches of the aortic arch and its bending degree. Dilation of the ascending aorta and alterations in the branching angles may be the key determinants of a high WSS that leads to type A dissection. Greater tortuosity of the aortic arch leads to stronger helical flow through the distal aortic arch, which may be related to tears in this region.

Numerical analysis of dynamic temperature in response to different levels of reactive hyperaemia in a three-dimensional image-based hand model.

Vascular reactivity (VR) is considered as an effective index to predict the risk of cardiovascular events. A cost-effective alternative technique used to evaluate VR called digital thermal monitoring (DTM) is based on the response of finger temperature to vessel occlusion and reperfusion. In this work, a simulation has been developed to investigate hand temperature in response to vessel occlusion and perfusion. The simulation consists of image-based mesh generation and finite element analysis of blood flow and heat transfer in tissues. In order to reconstruct a real geometric model of human hand, a computer programme including automatic image processing for sequential MR data and mesh generation based on the transfinite interpolation method is developed. In the finite element analysis part, blood flow perfused in solid tissues is considered as fluid phase through porous media. Heat transfer in tissues is described by Pennes bioheat equation and blood perfusion rate is obtained from Darcy velocities. Capillary pressure, blood perfusion and temperature distribution of hand are obtained. The results reveal that fingertip temperature is strongly dependent on larger arterial pressure. This simulation is of potential to quantify the indices used for evaluating the VR in DTM test if it is integrated with the haemodynamic model of blood circulation in upper limb.

Dynamic infrared imaging for analysis of fingertip temperature after cold water stimulation and neurothermal modeling study.

The human hand is considered to be the terminus of the nervous system. It contains numerous capillary vessels, and it plays an important role in the regulation of the autonomic nervous system. We have used infrared thermography and ultrasound Doppler flowmetry to investigate characteristics of the temperature variation of the hand and the blood flow after cold stimuli. We have also developed an image processing algorithm to measure temperature of various parts of the hand via sequential thermal images. Measured results show that local cold stimuli will induce oscillation of temperature, which may be due to neuroregulation during rewarming. Finally, in order to explain the mechanism of autonomic nervous system (ANS) regulation we have developed an ANS regulation model on the basis of the knowledge of the physiology and bioheat transfer. The results computed using our model are in good agreement with the experimental results.