Aortic disease is often associated with tissue degradation. However, the changes in the mechanical properties of the aorta occurring in accordance with tissue degradation remain unclear. This study explored the time course of the natural decay of aortic tissues in terms of mechanical and histological properties. Aortas excised from mice were incubated under ex vivo conditions, and their mechanical properties were assessed using a pressure–diameter test. Two linear lines were fitted to the pressure–diameter curve; the pressure at which the lines crossed was defined as the “collagen recruitment pressure”. During incubation, the aortas suddenly changed in stiffness, and the collagen recruitment pressure dropped abruptly. These rapid changes occurred significantly earlier under an intraluminal pressure of 0 than 100 mmHg. Histological examination revealed the loss of elastic laminas (ELs) and smooth muscle cells in the aorta, coinciding with the changes in mechanical properties. Thus, the rapid change was caused by sudden structural failure of the ELs, in which damage accumulated at the microscopic level over the incubation period. Additionally, the tissue degradation rate was dependent on the mechanical environment. These findings provide insight into the etiology of aortic diseases.

The reflux of pancreatic juice into the common bile duct and gallbladder is observed in the pancreaticobiliary maljunction (PBM) with various morphological characteristics of the biliary tract. However, the mechanism of pancreaticobiliary reflux (PBR) has not been clarified yet. Therefore, this study aimed to investigate the mechanism of PBR from the perspective of fluid mechanics. A mathematical model was developed for the bile and pancreatic juice flow based on the flow energy conservation law considering viscous pressure drop from the Hagen–Poiseuille law, fluid mass conservation law, and definition of gallbladder compliance. The flow simulation was computationally conducted using the statistically averaged morphological shape of the tracts and ducts. The simulated gallbladder volume rapidly increased after starting the refill, which was similar to the measured volume change of the human gallbladder. The calculated volume change rate and pressure waveform in the common channel was almost comparable to the measured value in humans. Our mathematical model may easily simulate the bile and pancreatic flow under various conditions. Therefore, it will be a powerful tool for understanding the mechanics of PBR.

During metastasis cancer cells pass through tiny gaps in blood vessel walls and between cells. Since the nucleus is the largest organelle in the cell and is much stiffer than the perinuclear cytoplasm, it may be a major physical constraint for metastasis. Here, we tested the hypothesis that cancer cells with higher metastatic potential have softer nuclei than those with lower metastatic potential. We performed a compression test on cell nuclei isolated from two metastatic B16 melanoma variants (B16-F1 and B16-F10) with different metastatic potentials. The results demonstrated that the nuclei isolated from B16-F1 cells, a lower metastatic cancer cell line, had a significantly higher Young’s modulus than B16-F10 cells, a higher metastatic cancer cell line. We also performed a compression test on the whole cell, encompassing the cell nucleus. Among similar whole-cell strains, B16-F10 cells showed a larger compressive strain in the intracellular nucleus than B16-F1 cells. In contrast, the force exerted on the intracellular nuclei of B16-F1 cells was similar to that of B16-F10 cells in the same whole-cell strain. These results suggest that B16-F10 cells may have adopted a strategy of enhancing the deformability of the cell nucleus to improve their metastatic potential.

We have developed a micro-porous covered stent (NCVC-CS1) for intracranial aneurysm (IA) treatment. Thrombus formation is locally promoted by flow diversion or isolation in the target IA after stenting, and the IA can be embolised. Despite using the same stent in clinical practice, the therapeutic effect may not be the same because the size and morphology of the IA and the parent vessel flow affect IA flow. Therefore, this study clarifies the influence of flow in a curved parent vessel on the flow diversion/isolation performance of the low-porosity stent using particle imaging velocimetry (PIV). In vitro experiments were conducted under steady flow conditions based on a flow similarity law using a two-dimensional parent vessel model with a saccular IA, a U-shaped parent vessel, and a simplified micro-porous film model. The results indicated that the area mean shear rate was well expressed by a power function using the Dean number. The cross-flow velocity component’s root mean square (RMS) perpendicular to the IA neck increased with a sharply curved vessel. In particular, when the curvature-radius ratio was larger than 1/2, the RMS of the cross-flow velocity remarkably increased despite stenting, suggesting that the stenting performance in a sharper-curved vessel is significantly affected.

Purpose: Our study investigated the risk of recanalization, from a hemodynamic perspective in six patients with visceral aneurysm embolization using coil packing, occasionally along with combined outflow vessel embolization. Methods: Blood flow simulations were performed using anatomically realistic vessel geometry created from the patient’s computed tomography images. A porous media model that represented flow in the embolized aneurysmal region was employed. Stagnant volume ratio (SVR) was evaluated to quantify the stagnation of flow within the embolized aneurysm. Results: SVR was elevated, with increased packing density (PD), in all patients. In the patient with recanalization, the rate of increase in SVR for PD <20% was smaller than that in the other five other patients, and the SVR for the actual PD was the lowest. In the five patients without recanalization, the SVR for the actual PD was greater than 80% at Reynolds number of 300. Conclusion: Individualized blood flow simulations focusing on SVR would be a useful tool to determine the clinical endpoint, the optimum individualized PD and to optimize postoperative follow-up of visceral aneurysms.

In this study, the concentration of the drug solution injected into the venous reservoir, which flowed into the patient, was measured in an in vitro model experiment and analyzed based on the law of conservation of mass within the parameters of flow rate using a blood pump. In the experiment, an aqueous KCl solution was injected into a venous reservoir using a syringe pump, and the concentration of potassium ions at the reservoir outlet was measured. The concentration of potassium ions changed according to a first-order lag, almost converging to that at the inlet. The time constant decreased with an increase in the flow rate of the blood pump. The concentration at the reservoir outlet was diluted with a small amount of the injected drug solution.

Mesenchymal stem cells (MSCs) have the potential to differentiate into endothelial cells (ECs) and become an attractive cell source for the application of therapeutic regenerative medicine. For developing highly efficient differentiation induction, we investigated the effect of a combination of biomechanical cyclic stretching and spheroid culture on MSC differentiation into endothelial cells. Spheroids were fabricated with adipose-derived stem cells (ADSCs), which were precultured with EC conditioned media and exposed to fluid shear stress for 3 days. After being cultured statically for 4 days in polydimethylsiloxane stretching chambers, the spheroids were exposed to 10% cyclic stretching at 1 Hz for 3 days. We confirmed that the spheroids maintained adhesion to the stretching chambers coated with 0.3 mg/ml type I collagen under the cyclic stretching condition. Meanwhile, the spheroids exhibited an elongated shape in response to the stretching. Real-time PCR analysis showed that the application of cyclic stretching to the ADSC spheroids induced EC-specific gene expression and hindered the other cell-type marks compared to the statically cultured spheroids. These results indicate that the combination of cyclic stretching and spheroid culture has the potential to efficiently induce EC differentiation of MSCs.

The diastolic function of the ventricle is evaluated using the ventricular diastolic pressure-volume (P-V) relationship, and the P-V relationship is generally quantified by the stiffness or the stiffness constant. The P-V relationship of humans and other mammals is often normalized with the ventricular lumen volume to exclude the size effect on ventricular stiffness; however, in amphibians and reptiles which have trabecular ventricles, the ventricular mass is used for normalization instead of the ventricular lumen volume, because it is difficult to accurately define the ventricular lumen. In the present study, we investigated the ventricular diastolic P-V relationships of anurans of different sizes, and demonstrated both mathematically and experimentally that the stiffness parameters obtained directly from the P-V relationship were inversely proportional to the ventricular mass. We also demonstrated that the volume of the natural ventricular lumen was proportional to the ventricular mass. These combined results indicate that the stiffness parameters obtained directly from the P-V relationship are essentially dependent on the ventricular size. Normalization of V with ventricular mass attenuated the size effect, and we confirmed that this method is useful for comparing the diastolic function between the trabecular ventricles of different sizes when focusing on material properties.

A stenosed blood vessel with a calcified part has complex shape and deformation properties. When using a catheter device in the blood vessel, a large deformation occurs, so the sensor needs to be flexible, and film sensors are used for contact force and pressure measurements during in vitro evaluations. Various flexible film sensors are available. However, capacitive sensors are widely used because of their simple structure and low power consumption. When using a balloon catheter in a calcified vessel, wide range of contact pressure may act on blood vessels, such as poor contact (less than the order of 1 kPa) and stress concentration areas (more than the order of 100 kPa). In this study, the performance of a capacitive film sensor is investigated over a wide pressure range 1–1000 kPa by focusing on the thickness and elastic modulus of its dielectric layer. The sensitivity of capacitance change is high for sensors with thin and soft dielectric layers. However, the sensor is considered to be more affected by creep deformation. The sensor can detect the contact pressure between the balloon catheter and the model vessel during balloon dilation. During the use of catheter devices through in vitro experiments using flexible film sensors, quantitative measurement of the load on blood vessels is useful for acquiring knowledge for application in clinical device selection and mechanical evaluation testing during new device development.

Circulating tumor cells (CTCs) are cancer cells that leak into the blood. CTCs can be captured using a set of microposts in a microchannel chip (CTC chip) that induces an antigen–antibody reaction. First, CTC capture experiments are performed on a conventional CTC chip at a flow rate Q = 1 mL/h. Subsequently, numerical simulation is performed using identical conditions to those employed in the experimental setup. A comparison between the numerical and experimental results shows that more CTCs are captured at a wall shear stress (WSS) ranging from 0.02 to 0.04 Pa. The existence of many walls with WSSs within the abovementioned range is effective for CTC capture. To investigate the effect of geometry, numerical simulations are performed under various post geometries. A channel with diamond-shaped posts (Square B model) shows that the WSSs of most walls ranged between 0.02 and 0.04 Pa at Q = 2 mL/h. A prototype of the new CTC chip with a Square B model geometry is fabricated, and its performance is evaluated. The results show that the CTC capture performance of the new CTC chip is significantly lower than that of conventional CTC chips. This indicates that post geometries significantly affect CTC capture performance.

Aortic dissection (AD) is a disease in which the tunica media is separated into two layers and blood flows in the newly created lumen. To elucidate the etiology of AD, we investigated the effect of the decrease in elastin, which occurs in actual AD, on the delamination strength of the aorta. Healthy porcine aortas were purchased, and half specimens were immersed in an elastase solution, for elastin digestion. The delamination test was performed on the specimens in both the circumferential θ and longitudinal z directions. The area fractions of elastin and collagen were measured via a histological analysis, such as Elastica–Masson and Azan stains. In healthy specimens, the delamination strength in the z-direction tended (albeit insignificantly) to be higher than that in the θ-direction. Conversely, in elastase-treated specimens, the delamination strengths in both directions were almost the same and were significantly lower than those recorded in the healthy specimens. The area fraction of elastin, but not of collagen, was significantly lower in elastase-treated specimens compared with control specimens. These results indicate that a decrease in elastin causes a reduction in the delamination strength, especially in the z-direction, which may result in dissection propagation in that direction in AD.

Abnormal hemodynamic conditions caused by a blood jet flow impinging on the aortic wall have been considered to be involved in the pathogenesis of aortic disease. Aortic diseases are generally accompanied by dysfunction and damage of the endothelial cells (ECs) lining the inner surface of blood vessels; however, the details of the effect of impinging jet flow on ECs remain unclear. In the present study, we investigated the effect of impinging jet flow conditions on the integrity of an EC monolayer. Human aortic ECs were exposed to an impinging jet flow with a maximum wall shear stress (WSS) of 18.6 Pa for 2 h in a newly developed cylindrical T-shaped flow chamber. Consequently, the ECs were detached only in the region where the WSS and normal flow velocity immediately above the wall were high. Decreased expression of the intercellular junction molecule, PECAM-1, was also observed in this region. Multiple regression analysis revealed that EC density and PECAM-1 expression were significantly correlated with not only the WSS and WSS gradient but also the normal flow velocity. Our findings suggest that the distinctive mechanical environment under an impinging jet flow may disrupt endothelial integrity.

High cardiac pump function in mammals and birds requires the elaborate control of calcium (Ca²⁺) concentrations in cardiomyocytes (CMs). Previously, we reported that avian quail CMs have a higher capacity for Ca²⁺ efflux than mammalian rats, but the decrease in Ca²⁺ concentration estimated using the fluorescent Ca²⁺ indicator Fura-2 was slower than that expected from the observation of cell relaxation behavior. In this study, we examined changes in Ca²⁺ concentration in quail and rat CMs using Fura-4F, which allows for more rapid tracking of changes in Ca²⁺ concentrations than Fura-2. The results demonstrated that, compared to Fura-2, Fura-4F showed a narrower dynamic range but a more rapid response to changes in Ca²⁺ concentration. Furthermore, Fura-4F showed that the Ca²⁺ concentration in quail CMs decreased significantly faster than that in rat CMs after electrical stimulation. These results are qualitatively consistent with our previous study using Fura-2 and therefore reinforce the conclusion that the Ca²⁺ removal capacity of quail CMs is higher than that of rat CMs.

The lipid bilayer is the essential component of the cell membrane to provide some structural support for a cell and control transport of materials entering and exiting the cell. Since it has a centrosymmetric structure, the second harmonic generation (SHG) signal can hardly be observed from the membrane. Adding a dye to the lipid molecules in outside layer makes the lipid bilayer non-centrosymmetric and enables it to generate observable SHG signals. Physical disturbances of the membrane would lead to reallocation and transmembrane migration of molecules including dyes, thereby making the lipid layer structure homogeneous and centrosymmetric and consequently diminishing the SHG signal. If so, a change in the membrane structure could be imaged based on the SHG signal intensity. The present study therefore aims to seek for a feasibility of imaging the membrane damage via SHG signal measurement. Moreover, the present study investigates how the SHG signal change varies depending on the frequency of electric stimulations that are used as a damage source. Liposomes were used as a cell membrane model. The SHG signal intensity of liposomes loaded with the SHG-specific dye, Ap3, during electric stimulations was observed using a multiphoton microscope. The results demonstrated that the SHG signal intensity of the membrane decreased with the repetitive application of the electric pulse. While the SHG signal decay was faster as the time interval between consecutive electric pulses was shorter, no remarkable decay was found for longer time intervals. The trend was explained by membrane healing or pore resealing during a time interval between consecutive electric pulses which prevented transmembrane migration of Ap3. The results suggested that the membrane structure change could be imaged based on the SHG signal measurement.

To understand the swelling and hemolysis behavior of human red blood cells (RBCs) due to the osmotic pressure difference, we have observed the temporal changes in shape, volume and hemoglobin (Hb) content of the RBC. In particular, the present study focused on a single RBC and aimed to construct an experimental method to simultaneously measure the above-mentioned changes. Adding a hypotonic solution of 0.1 wt% NaCl aq. into the isotonic RBC suspension, we experimentally observed an RBC swelling from the biconcave disk to the spheroidal and spherical shape. From the two-dimensional images obtained in the experiments, the time evolution of the surface area and the volume of the RBC was estimated on the assumption of the axisymmetric geometry. In addition, by using a light source with the Hb absorbance wavelength during the experiments, we succeeded in measuring the time variation of Hb content in the RBC simultaneously with the shape and volume changes. From a series of the results, it was found that the volume of RBCs reached a maximum when their shape became almost spherical, and the leaching of Hb began after that.

Particle imaging velocimetry (PIV) is an effective methodology for investigating flow in the neo-sinus after transcatheter aortic valve replacement. However, understanding fluid dynamics in the lower part of the neo-sinus has been challenging due to limited optical access. In this study, we developed a novel PIV technique to extensively visualize the neo-sinus and to assess the potential risk of transcatheter heart valve (THV) leaflet thrombosis with the intra-annular valve. This technique involved shooting in the sinus and neo-sinus via the ventral wall of the aortic silicone model to visualize a larger region of the neo-sinus, including the lower portions (overlooking-view shooting). In the neo-sinus, stagnated flow was observed throughout the entire region in middle and late diastole. By contrast, in the native sinus, low-velocity vortical flow that inflows into the coronary artery was developed exclusively in the upper region. The present results suggest that the lower portion of the native sinus, as well as the neo-sinus, may be at high risk for leaflet thrombosis. The novel PIV technique holds promise for revealing influences of fluid dynamics on THV leaflet thrombosis with various stent flame designs.