For the treatment of cerebral aneurysms, flow diverter (FD) stent placement has been attracted. To evaluate a positioning error of stent on aneurysm flow, we analyze an influence of strut positions with relation to the inflow zone. Lattice Boltzmann flow simulation was applied to compute flow velocity in 3-D ideal aneurysm with a curved parent artery. Rectangular solid as a strut model was placed along to the neck plane. The results suggest that the flow velocity in the aneurysm is effectively reduced when the flow in the aneurysm and parent vessel flow are separated by a strut.

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Stent grafting is one of the treatments for thoracic aortic aneurysm that is less invasive than open surgery. However, it sometimes involves in serious problems: Endoleak and Migration. These problems seem to have a relation to the oversize of stent or wrong position of stent on the arterial wall, and so the evaluation of the problems should be performed quantitatively using in-vitro model with observation of sealing. The purpose of this research is the development of in vitro model made of PVA-H (Poly Vinyl Alcohol Hydrogel) for evaluation of endoleak and migration on stent graft. We used Dip-Coating method to make the model. Dip-Coating is the method which forms a liquid film on the surface of the mold (Nylon12) by dipping the mold in PVA-H. As the result, the method using Nylon12 as a material of the mold enables to make the model with a similar surface roughness to the conventional method. In addition, the model has a high transparency and will be used for PIV.

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We have developed a device placement simulator for endovascular treatment. In this study, we evaluated the coil embolization of an aneurysm using this simulation system. The model of the catheter and coil are constructed with viscoelastic springs and segments as the dynamic deformation of a flexible structure. The vessel is an elastic circular cylinder, whose shape is defined by the centerline and the radii. We consider the contacts between the coils, the catheter, the vessel and the aneurysm. We the investigated influences of the catheter's position on the coil's behavior. The catheter's position has a great influence on the coil's behavior. Depending on the position of the catheter, the coil is not inserted along the curved surface of the aneurysm. When the coil is not inserted along the curved surface of the aneurysm, the position of the coil is not stable.

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We have developed a computer-based system to simulate a guidewire and a catheter in blood vessels for surgical planning, intra-operative assistance, and to facilitate the design of new guidewires and catheters. We have also developed an experimental apparatus which can be used not only for the validation of the numerical analyses but also as a simulation system. However, we have not evaluated the catheter motion in the experimental apparatus. Therefore in this study, first we added a mechanism to move the catheter to the experimental apparatus. Second, we evaluated the deformation behaviors of the guidewire and the catheter by the measurement of the 3D position and the contact force between the medical devices and the vessel. Finally, we compared the calculation results with the experimental results. The same tendency was seen in the trajectories and the contact force of both the experimental and calculated guidewire and catheter tips.

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In this study, we fabricated a prototype catheter type tactile sensor composed of two polyvinylidene fluoride (PVDF) films and evaluated the data acquisition and processing by the sensor to detect the diseased part in a blood vessel. The PVDF films, which have stress (strain) rate dependent output, are located in a silicon rubber cylinder whose outer diameter is 5 [mm]. We inserted the prototype sensor into a blood vessel model whose inner shape was partially changed assuming that these changes occur by a disease. The vessel model consists of a tube whose inner diameter is 8 [mm]. The sensor can detect the position of the projections in the tube. Moreover, peak-to-peak value of the sensor output voltage increases according to the insertion speed. In addition, we can evaluate the surface roughness inside the tube by fourier transform of the sensor output. In the future, we hope to evaluate the sensor with a more practical prototype.

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For early diagnosis of atherosclerosis, functional assessments of endothelial cells (ECs) and smooth muscle cells (SMCs) are important. EC function has been evaluated with flow mediated dilation (FMD) test. Evaluation of SMC function has not been established. To evaluate SMC contractility, we developed a pressure mediated contraction (PMC) method in which myogenic contraction of the human brachial artery is induced by applying 50 mmHg of negative pressure to an airtight chamber attached to the arm for 120 s. One of the problems of this method was found to be displacement of brachial artery following negative pressure application. To overcome this problem, we developed a method to evaluate SMC function by measuring myogenic response of the artery by applying chopped positive (20-30 mmHg) or negative pressure (-50 mmHg) synchronized with electrocardiogram. By measuring arterial diameter during unloading phase, the displacement of artery caused by the pressure loading could be reduced markedly from 2.98±1.17 mm (mean ± SD, n = 8) for conventional PMC to 0.20±0.09 mm (n = 8). We also observed that the rate of arterial relaxation under chopped positive pressure was 5.3 ± 1.2 % (n = 6), while that of arterial contraction under chopped negative pressure was 10.2±3.1 % (n = 6). This may indicate that artery has more room for contraction than for relaxation, which is beneficial against sudden decrease in blood pressure.

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There is a need for new methods to measure the level of arterial stiffness easily at home. A previous report investigating the effect of measurement position on brachial-ankle pulse wave velocity (baPWV) showed that baPWV were higher in the sitting position than in the supine position. This was probably because the increased ankle PWV was associated with increased hydrostatic pressure in the arteries of lower extremities. Therefore, we investigated the effect of measurement position on the cardio-ankle vascular index (CAVI), which is hardly affected by blood pressure. CAVI was measured in 50 healthy males (20-74 years) in five positions: supine, sitting, sitting with the knees flexed at 0°, reclining 50°, and standing. Compared to other positions, CAVI in the supine position was the lowest (P < 0.01); t_b (the time difference between the second heart sound and the notch of the pulse wave in the upper arm) in the supine position was the highest (P < 0.01); and t_<ba> (the time difference between the minimum upper arm and ankle pulse wave pattern values) in the supine position was the highest (P < 0.01). Thus, our results indicated that changes in measurement position reduced pulse arrival time (increasing pulse wave velocity). We also observed a strong correlation between CAVI in the supine position and that in other positions. The present study showed that the measurement position affected CAVI as much as it affected baPWV. Accordingly, correcting for the measurement position would be required when the position differs from supine.

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To clarify the mechanism of cerebral blood flow (CBF) regulation in the functioning brains, we compared the activity-induced change in a vessel diameter between the cortical surface arteries and penetrating arterioles, where those vessels have a different role in controlling a spatial distribution of blood flow supply. The measurements were conducted with two-photon microscopy in the anesthetized rat cerebral cortex, while electrical stimulation to nucleus basalis of Meynert (NBM) or forepaw (FP) of the animals was applied with and without pharmacological load. We observed that stimulation to the NBM induced vasodilatation of the penetrating arterioles, but not the surface arteries, whereas the FP stimulation induced a dilation of the both arteries. The results were consistent with our previous reports studied in the anesthetized mouse cortex. Furthermore, a pharmacological inhibition of the acetylcholine receptor activity suppressed the responses of the both arteries to the stimuli. These observations support the notion that the vasodilation mechanisms driven by activity of the NBM partly participate in the CBF response to the sensory stimulation.

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Rupture of atheromatous plaque in carotid arteries causes cerebrovascular events which can lead to death. The mechanical behavior of the ruptured plaque is not yet fully understood. Finite element (FE) analysis gives insight to the mechanical behavior of the ruptured plaque. In this study we focused on the post-rupture deformation of a plaque in an internal carotid artery (ICA). We created tubular solid and fluid FE models of the ruptured ICA. We compared the simulation results with ultrasonographic images taken before endarterectomy. Pressure in the lipid core (LC) cavity was equal to the intraluminal pressure at the site of rupture, and its volume was nearly doubled. However, the volume of LC was overestimated compared to what observed in vivo. These are in accordance with literature studies which reported blood entering a ruptured plaque with an increase in plaque volume. Our results provide a better understanding of the mechanism and behaviour of the plaque post-rupture, which may improve its medical evaluations.

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Transcatheter aortic valve replacement (TAVI) is a less invasive therapy and the number of operations is increasing. In some operations of TAVI, valve annulus rupture and failure were happened. Strain measurement method in the blood vessel has not been established and there is no way to evaluate the strain distribution experimentally. It is difficult to measure large deformation of the blood vessel using conventional digital volume correlation with computed tomography. This study presents a new strain measurement method of an elastic blood vessel model using the displacement distribution measured by tomographic particle image velocimetry. Tracer particles were distributed in the blood vessel model and displacement distribution was measured by tracking the particles. The displacement measuring accuracy affected by the amount of displacement and spatial resolutions was assessed. The strain yielded in the blood vessel model, when it was 10% expanded, was measured in the optimal condition determined by the accuracy measurement. In this study, the optimal displacement spatial resolutions and displacement condition were 64 X 64 X 64 voxel^3 and 90-150 μm respectively. This experimental investigation revealed that the higher strain was yielded in the inner wall of the blood vessel model and the strain becomes lower toward the outer wall.

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To clarify the effect of blood vessel elasticity in the cerebral aneurysm, the measurement of velocity vector at the blood flow waveform in the elastic and rigid aneurysm models was measured by particle image velocimetry (PIV). These models were constructed of silicone resin and simulated the geometry of a saccular aneurysm at middle cerebral artery (MCA). PIV measurements was carried out at the maximum Reynolds number of 700 and for the Womersley number of 1.41 in middle cerebral artery (MCA: M1). A roller pump controlled the flow waveform and the flow rate. The big difference of inflow from the neck was found: the rigid model had flow along the wall on the other hand the elastic model had one away from the wall. This difference was caused by elasticity of aneurysm model. This indicates that the effect of blood vessel elasticity is important.

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Information on hemodynamics is essential for elucidation of mechanisms and development of novel diagnostic methods for circulatory diseases. Two-dimensional ultrasonic-measurement-integrated (2D-UMI) blood flow analysis system provides detailed information on intravascular hemodynamics by feeding back an ultrasonic measurement to a numerical blood flow simulation. The purpose of this study was to clarify analysis accuracy of velocity vectors in 2D-UMI blood flow analysis. 2D-UMI analysis was performed for ultrasonic measurement data of a steady flow of blood-mimicking fluid in a model of a human carotid artery with a stenosis, and the analysis result was compared with corresponding three-dimensional computational fluid dynamics (3D-CFD) analysis result. As a result, the velocity vector profile deflected to the lower wall side obtained in 3D-CFD analysis result was properly reproduced in the 2D-UMI analysis.

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In the fields of forensic medicine, the development of a simulation model of bleeding to assist in clinical observation is desired. Zero-dimensional simulation models that have a low computational load are effective for performance of lengthy analysis such as the decrease of blood pressure caused by bleeding. The purpose of this study was to expand the zero-dimensional cardiovascular system model by Hanzawa et al. to an internal and external human body blood flow simulation model by considering bleeding. Bleeding was simulated by setting an outflow at an arbitrary point in the simulation model. The validity of the proposed model was examined by analyzing the effect of bleeding on the behavior of the cardiovascular system. Due to bleeding, pressure decline and volume decrease were observed in each part of the cardiovascular system. With respect to the pressure decline, a rapid pressure decline and a slow pressure decline were observed. The rapid pressure decline was observed in the aorta and left ventricle. This is a result of the increase in the flow rate due to bleeding. On the other hand, the slow pressure decline was observed in the whole cardiovascular system. This is caused by the decrease in the total volume of the cardiovascular system.

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The present study was aimed to develop a mapping method for blood flow velocity of the cortical arteries and veins in the anesthetized mice. The cortical region where the skin and skull was removed was continuously imaged with confocal laser scanning fluorescence microscopy at a rate of 20-76 frame per sec, while a small amount of the fluorescent dye (20 μL) was injected through the tail vein. A transit of the dye in the cerebral microcirculation was tracked, and a traveling time and distance of the dye through the vasculature was measured with custom written software to create a velocity map. The result showed a good linear correlation was shown between the flow velocity and a diameter of the vessel in the arteries, but not in the veins. The results demonstrate that the proposed method for mapping of the flow velocity will be a valuable tool to explore the cellular interactions among brain cells, vascular cells, and blood flow velocity in the functioning brains.

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Recently, the population of diabetic patients has been increasing in the world. The diabetic patients need to measure blood glucose level constantly by themselves to cure. However, it burdens the patients because most blood glucose level measurement devices require drawing blood. In order to solve this problem, we have developed a noninvasive blood glucose level measurement based on photoacoustic spectroscopy (PAS). This method is required to measure a sound wave generated by absorbing modulated light. However, there are several problems such as sensitivity and portability. In order to improve these, we focused on a shape of an acoustic cell to sense the sound wave. In this study, I-shaped cell was proposed. We evaluated an effectiveness of the I-shaped cell by comparing with a conventional resonant cell using finite element method (FEM). As a result, the sensitivity of I-shaped cell was 17.9 [dB] larger than that of the conventional resonant cell. In addition, the I-shaped cell's volume was about one-fiftieth of the conventional resonant cell's volume.

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Obesity and metabolic syndrome which are currently social problems, are thought to be caused by the accumulation of lipid droplets in the body. It is important to develop the screening system for functional foods to treat the obesity or metabolic syndrome. Since fat tissue has a high impedance values, it is considered that the amount of lipid droplets affect the impedance value. Therefore, culturing adipocytes and monitoring their electric impedance simultaneously would enable to evaluate the amount of lipid droplets. In this study, mouse fibroblasts 3T3-L1 were cultured on comb-shaped indium-tin oxide electrodes and the electric impedance measurements were performed to evaluate adipogenesis and lipid accumulation. Briefly, the fibroblasts were cultured under two conditions (with and without adipogenesis) and the real and imaginary parts of impedance were measured. As the results, the imaginary part of impedance of fibroblasts under adipogenesis condition showed different response compared to that under without adipogenesis condition.

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In the field of regenerative medicine, it is expected to separate disease-causing cells from healthy cells by electrical method with label-free and high efficiency. The purpose of this study is to find the velocity differences between disease-causing cells and healthy cells under AC electric field in an electrodes multilayered microchannel. We prepared intracellular charge differed three cell types: wild type cells (WT), wild type cells with green fluorescent protein (GFPT) and wild type cells with green fluorescent protein histone (GFP-HT). The cell dynamic movement of each type was detected by Particle Tracking Velocimetry method. Velocity differences were found and discussed among WT, GFPT and GFP-HT around the AC voltage applied electrode. The present results provide a great significance for separation of disease-causing cells from healthy cells by histone numbers in the microchannel.

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We have developed a cast microfluidic chip that contains a thin (〜0.5 μm wide) microchannel that is smoothly connected to thick microfluidics. The thin line features having high aspect ratio for a low-cost photolithography in which an emulsion photomask was used (1:1〜1:3) were fabricated by exposing SU-8 photoresist to diffused 185 nm UV light emitted by a low-cost ozone lamp from the backside of the substrate to ensure sufficient crosslinking of small regions of the SU-8 photoresist. An T-shaped microfluidic configuration was used, in which the thin channel maintained constant diffusion fronts beyond purely static diffusion. T-head-formed microfluid constitution was used, in which we performed the evaluation that the thin waterway could maintain the constant concentration gradient across the totally static spread. By using this device, we can generate the concentration gradient, and maintain the concentration gradient for 6days. This result was caused by hydrostatic pressure at reservoir. We may be able to control the concentration gradient condition by controlling hydrostatic pressure.

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Glioma is a type of malignant brain tumor. Despite the current progress of radiation and chemotherapy regimens, tumor prognosis is still poor. Since gliomas rapidly invade normal brain tissues, most of them are diagnosed at an advanced stage. Thus, a better understanding of glioma tumorigenesis and characteristics is very important for brain tumor therapy. Previous in vitro studies, which were usually performed by using conventional tumor cell lines in the 2D culture environment, failed to show the similarity to human glioma. Here we used glioma-initiating cells (GIC) which were established by gene transfection. In this study, we proposed a new in vitro assay model created in a 3D microfluidic device. This model allowed us to investigate the invasion process of GIC cocultured with human umbilical vein endothelial cells (HUVEC). We found that GIC invasiveness in coculture was higher than that in monoculture. We also found that GIC formed cell clusters in monoculture. These results suggest that HUVEC promoted the GIC invasiveness through weakening their intercellular adhesion.

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In this study, we have measured deformability of malaria parasite-infected human red blood cells (RBCs) using dielectrophoresis (DEP) to elucidate the relation between the cell deformability and the infection stage depending on the different strains of malaria parasite. Severe malaria is still a major infectious disease caused by a protozoan parasite Plasmodium falciparum in tropical and subtropical regions in the world. Malaria parasite invades RBC and proliferate within RBC. It is documented in previous research that the membrane of P. falciparum-infected RBCs becomes indurated. However, the mechanism of this phenomenon remains to be elucidated. Here, we propose on-chip method for a tensile testing of RBC that is able to quantify mechanical proportion and can be used to evaluate the parasite's gene function in combination with the genetic engineering techniques for this parasite. We found that the dielectrophoretic deformation of the host RBCs showed different tendency depending on the parasite-strains. Moreover, we were able to estimate Young's modulus of the infected RBCs from the result of the tensile test. These results indicate that the developed method for the detection of RBCs infected by malaria parasite, but also in future association studies between the mechanical property of the parasite-infected RBCs and malaria pathogenesis.

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We developed a novel device which separates blood plasma from a minute amount of whole blood using tilted microchannels. Blood cell sedimentation is enhanced in a tilted channel, and its velocity is much larger than in a vertically-placed channel. This phenomenon is called the Boycott effect. The blood separation device had three microchannels which are made of PDMS and measure 100 μm in depth, and their ends were connected at one point. The two channels were tilted at a 45 degrees angle and used for blood separation. The other channel was placed vertically and used for blood sample injection. When a blood sample was placed at the entrance of the injection channel, the blood automatically entered the channels by capillary force. Then, blood cell sedimentation at the connection of the channels was observed using a CCD camera. The experimental results showed that the sedimentation velocity increased with an increase of length of the blood separation channel. We succeeded in obtaining a sedimentation length of 100 μm in 1.5 min using the 20 mm long separation channel.

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We developed a microdevice for detection of Deoxyribonuclease (DNase), which is a candidate biomarker for acute myocardial infarction. DNA metallization process using intercalator molecules labeled with reducing groups permits double-stranded DNA to be specifically metallized while not permitting metallization of single-stranded DNA. Using this process, we metallized DNA complexes consisting of single strands and double strands, and fabricated partially-metallized DNA nanowires. In this paper, multiple partially-metallized DNA nanowires were immobilized between two electrodes in a microchannel, and DNase detection was achieved by measuring the increase in impedance between the electrodes after DNA cleavage by DNase. The use of partially-metallized DNA nanowires having much smaller impedance compared to non-metallized DNA generates a drastic increase of impedance after their cleavage and therefore permits much higher sensitivity. The experimental results showed a definite correlation between DNase concentration and impedance increase rate in range of 10^<-6> to 10^<-1> unit/μl of DNase. The present study will make DNase detection more simple, rapid, sensitive than conventional fluorometric and electrochemical detections.

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For molecular analysis of the rare cells, such as Circulating Tumor Cells (CTCs), the single rare cell isolation and pick-up from sample is required. Here, we propose the development of a microfluidic chip for isolating single CTCs from blood samples. Drag force and capillary force are used to trap CTCs on a microfluidic chip with open channels. CTCs are carried to the meniscus of air-liquid interface due to the drag force generated by a syringe pump. Single CTCs are then trapped into pockets of the microfluidic chip due to the capillary force acting at the meniscus of air-liquid interface. After isolation, trapped single CTCs can be recovered from the microfluidic chip using micropipette.

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This paper presents a method of detecting viral RNA by using Quartz Crystal Microbalance (QCM). QCM is mass sensor for detecting biomolecules. We fabricated microfluidic chip with QCM and immobilized Peptide Nucleic Acid (PNA) on the surface of the electrode of QCM. PNA is one of the artificial nucleic acid and it can capture viral RNA specifically. Therefore, we used the gold nanoparticles conjugated anti-nucleoprotein antibody to increase sensing mass and improve sensing limit of QCM. As a result, we succeeded in detecting viral RNA (5 x 10^3 pfu).

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In the present study, experimental and numerical studies of dielectrophoretic (DEP) flow channel, a type of cell-separation devices that exploits the differences in the dielectric properties of cells, was conducted to design and propose a high-performance cell-separation DEP device. The cell samples used were live and dead cultured budding yeast cells suspended in water. The cell-separation analysis was carried out for the flow channel equipped with a planar electrode on the top face and an array of micro-fabricated electrodes on the bottom face; yielding a three dimensional non-uniform electric field across the full height of the flow channel. To determine the optimal separation condition for live and dead cell-mixtures, the value of the field frequency was varied in several ways. With the appropriately chosen operating condition, the live cells were effectively attracted toward the edges of electrodes on the bottom while the most of the dead cells continued to travel in the flow. The performance improvement of DEP cell-separation device can be expected by using the concept of the proposed device.

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A cell manipulation is important technology to develop novel medical therapy and medical applications. AC electrokinetics is useful for the cell manipulation. The applied electric field in the cell dispersion generates forces on cells with dielectrophoresis (DEP) and flows caused by the AC electrokinetics. The system of sharp tip electrode with AC electrokinetics is one of the optimal combinations to manipulate cells for biological and medical applications. In this study, hepatocytes motion and the fluid flow were investigated using the sharp tip electrode under several applied voltage conditions, applied frequency conditions, the particle size and liquid conductivity. The characteristics of the cell manipulation and the generating mechanism of the electric induced flow with AC electroosmosis were investigated.

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This study demonstrates two-dimensional (2D) cell patterning using label-free magnetic cell assembly method. In this patterning method, we added a paramagnetic salt, gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) to increase the magnetic susceptibility of the medium. As a result, the cells act as a diamagnetic particle and can be manipulated by magnetic force without magnetic labeling. First, we examined the magnet array using a finite element method based software and determined the suitable arrangement for line and space patterning that consisted of neodymium magnets 1 mm in thickness and Teflon sheets 0.1 mm in thickness. Next, mouse fibroblast cell NIH 3T3 cells were patterned using the magnet array. One hour later, almost all cells were confined in the area 300 μm in width at intervals of 1100 μm. The result indicates that the label-free magnetic cell assembly method can be applicable for 2D cell patterning and suitable for cell patterning in closed space such as a microchannel.

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We propose a sheet shape controlling method of tens/hundreds-nm-thick polymer film (called "nanosheet") by using a triple-layered structure and consider composition of the triple-layered structure. The triple-layered structure includes a nanosheet, a stretching layer with internal stress and a supporting layer. The supporting layer and the stretching layer were dissolved in water. The triple-layered structure was folded into a cylindrical shape due to the internal stress and unfolded into a flat shape after dissolution of a stretching layer. In this paper, we considered the solubility and swelling property of the supporting layer and the stretching layer, and considered compositions of the triple-layered structure which is a parameter of unfolding. After soaking in water, Type-A composition (stretching layer - supporting layer - nanosheet) was unfolded into a flat shape, and immediately after folded into a cylindrical shape because of swelling strain mismatch of supporting layer and stretching layer. However, Type-B composition (stretching layer - nanosheet - supporting layer) was able to keep a flat shape after unfolding because swelling strain of the stretching layer and the supporting layer were the same. Therefore, the type-B composition can reduce influence of swelling.

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The purpose of this research was to measure thumbnail strain when grasping an cylindrical object and to determine whether asymmetric strain distribution occurs in the radioulnar direction. In addition, we examined the effects of object size and thumb-pressing force. Biaxial strain gauges were attached at three locations on the thumbnail surface (central, radial, and ulnar parts). Each axis of the biaxial strain gauges was aligned to the axial and transverse directions, respectively. The diameter of the cylindrical object were 50mm, 60mm, 80mm, 100mm, and 120mm. The thumb-pressing force were 1N, 3N, and 5N. When the diameter of the cylindrical object was small, the distribution of strain in the axial and transverse directions was asymmetric; however, when the diameter of the cylindrical object became large, the asymmetric nature of the strain distribution in transverse direction disappeared. The thumb-pressing force affected the ulnar strain, but not the radial strain. When grasping a small object, the ulnar surface of the thumb pad is an important contact surface. This was the factor in asymmetric strain distribution occurring in the radioulnar direction. When grasping a large object, the contact surface moves to the center of the fingerpad; however, it was assumed that the asymmetric strain distribution occurred because of the asymmetric nature of the internal structure of the thumb.

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In order to reveal the relationship between the deformed shape of the brassiere-wearing breast and the internal tissue distributions of the breast, the finite element (FE) simulations were applied to the two women's individual breast shapes. Mammary tissues were assumed as Neo-Hookean hyperelastic model in order to reproduce the MRI experimental results. The lift-up simulations of two kind of brassieres, 3/4-cup type and full-cup one, were tried with changing the material properties of the mammary glandular region under gravity loading. The FE results had good agreements with the MRI measurements. These results indicate the importance not only of the mammary glandular ratio for more cosmetic wearing designs of brassieres.

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Skin has three main functions: protection, regulation and sensation. The extensibility and elasticity of soft tissues such as skins are probably attributable to the quality and quantity of elastin fibers. However, the biomechanical contribution of elastin to the skin properties remains unknown. Our overall goal was to clarify the mechanical function of elastin in soft tissues and to determine whether the external medication of elastin ingredients is effective for the maintenance and improvement of the skin extensibility. Specifically, we focused on the deformation recovery behavior after tensile loads were applied to skin tissues. Elastin ingredients were obtained from aortic bulbs of young yellowtail. In the present study, biomechanical tests were conducted for hairless mouse skins irradiated with ultraviolet light. The mice of 18 weeks old were used for the experiment. We irradiated the ultraviolet to hairless mouse back skins (UV group). Irradiation of ultraviolet was performed for 18 weeks. The ultraviolet-irradiated skins applied elastin and placebo lotion were used to obtain the data for the E-lotion and P-lotion groups, respectively. Data for the non-treated, normal skins were also obtained (Control group). The elastic recovery strain and recovery strain rate in the E-lotion group were higher than those in the UV and P-lotion groups. There were no significant differences in the both parameters between the Control and E-lotion groups. From these results, we can say that elastin components were closely related to the dermal functions as well as the healing processes and diseases of skins. The finding of the present study would be useful as basic knowledge for the development of novel medicine to prevent the skin aging and diseases.

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Micro slurry-jet erosion has been proposed as a precision machining technique for the bearing surfaces against a soft or hydrated material. The micro slurry-jet erosion method is a wet blasting technique which uses alumina particles as the abrasive medium along with compressed air and water to create an ideal surface. The technique will be one of the effective tool to create LOTUS-LEAVES or MOTH-EYES structures, the inspiration for the incredible properties of the new coating comes from nature. The water repellent and self-cleaning abilities resemble those of LOTUS-LEAVES, which use rain for self-cleaning, the surface should be angled at about 150 degrees, causing the water drops to bounce off and take dust along with them. The boost of efficiency comes from an anti-reflective technology that resembles MOTH-EYES in functionality and structure. Thanks to advances in the nano-scaled machining technique, the authors will be able to engineer precisely the nanoscale structures in the future.

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Researchers have reported that there are some correlations between the morphological aspects of wear debris generated from an ultra-high molecular weight polyethylene (UHMWPE) in an artificial joint and the biological response induced by the debris. The wear particles stimulate macrophages, and production of inflammatory cytokine may induce osteolysis, that leads to joint loosening. It was reported that the production of inflammatory cytokine was influenced by the particle size, where the size less than 1.0 mm seemed to be important. A nano-scale textured surface on a Co-28Cr-6Mo alloy, as a counter face material of UHMWPE, is proposed in this study in order to control the volume of wear and the morphological aspect of UHMWPE. The textured surface could reduce the total amount of UHMWPE wear and the size distribution of wear debris, where the particle size was getting larger. The wear particles produced by the textured surface reduced the production of inflammatory cytokine IL-6 in culture supernatant. These results suggested that a prolongation of service life in artificial joint would be possible by the modification of surface profile at nano-scale.

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Magnetic fluid is the material that the magnetic fine particles is dispersed uniformly by a dispersant in solvent. In this study, we designed and manufactured the magnetic fluid which has a biocompatibility and a superior magnetic characteristic by using the PEGylated polyacrylic acid (PAA) as a new dispersant instead of the chondroitin sulfate C which we used before. Furthermore, we evaluate influences on characteristics such as the mean colloidal diameter, the magnetic characteristic, mean diameter of the magnetic fine particles and the composition of magnetic fluid by the PEGylation. First, Fourier Transform Infrared Spectrophotometer was used to confirm the bond of PEGylated PAA. As a result, it was confirmed the PAA was PEGylated. Next, the mean colloidal diameters were investigated by using Dynamic Light Scatting. This experience yields that mean colloidal diameter tend to increase by PEGylation. Also, to investigate the magnetic characteristic, the magnetization curves were acquired by using Vibrating Sample Magnetometer. So that, it was recognized that magnetic characteristic decreased by increasing ratios of compounded PEG. In addition, the composition of magnetic fine particles was analyzed by using X-Ray Diffractometer. And the magnetic body of the γ-Fe_2O_3 was recognized as a core like the magnetic fluid using the chondroitin sulfate C. Furthermore, magnetic fine particles were photographed by Transmission Electron Microscope and the mean core particle diameters were measured from the image. As a result, composition of the PEGylation didn't influence the core particle diameters.

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A drug delivery system (DDS) device that consists of microspheres and polymeric film was fabricated and tested. Collagen microspheres (COLs) were embedded in photopolymerized polyethylene glycol dimethacrylate (PEGDM) film. The result showed COLs in the film were uniformly distributed and parts of COLs were exposed on the surface of the device. In vitro release study confirmed that devices could release FITC-dextran (FD40) continuously for over 10 days. It is found that there is a linear relationship between self-deployment time and the number of turns of the sheet. The flexible sheet type device that is injectable by a syringe needle holds great promise to locally deliver drug to specific organs such as eye or bladder.

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This paper presents the creation of heterologous cell pattern by cell culture surface processing technique based on photolithography. The alginate gel was used as cell adhesion inhibition material. The alginate gel was formed on a glass plate by spin-coating. The alginate gel pattern was created by wet etching process or lift-off process along the pattern of photoresist. The cell micropattern was created along the alginate gel micropattern. The alginate gel micropattern that inhibits adhesion of cells was removed by ethylenediaminetetraacetic acid (EDTA). After removing the alginate gel pattern, new cells were disseminated to the same dish, and new cells adhered to the alginate gel removed section. Heterologous cell pattern was created by patterning of the alginate gel based on photolithography.

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This study aims at forming a fluorescent complex between HAp coatings with ligands of amino acid by using CIP process in order to suppress cytotoxicity of conventional fluorescent HAp complex and also enhance antibacterial properties by visible light irradiation. Three amino acids, phenylalanine, tryptophan and tyrosine were used in the CIP process. By applying pressures from 200 MPa to 800 MPa, fluorescence of HAp with the three amino acids was successfully observed by UV irradiations. In the case of highly compressed samples, fluorescence in some regions was shifted to longer wavelength. Cytotoxicity assessments were conducted by using MC3T3-E1 osteoblast cells. Observing optical density of mediums after cultivations revealed that there were no significant differences among five groups in cases of same culture periods. The results demonstrated that biocompatibility of HAp/amino acid complex was similar to HAp itself.

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Hydrogel-based, molecular permeable electronic devices are considered to be promising for electrical stimulation and recording of living tissues, either in vivo or in vitro. This study reports the fabrication of the hydrogel-based devices that remain highly electrically conductive under substantial stretch and bending. Using a simple technique involving a combination of chemical polymerization and electropolymerization of poly (3,4-ethylenedioxythiophene) (PEDOT), a tight bonding of a conductive composite of PEDOT and polyurethane (PU) to an elastic double-network hydrogel is achieved to make fully organic PEDOT/PU-hydrogel hybrids. Their response to repeated mechanical stretching, hydration-drying cycles, and autoclaving is assessed, demonstrating excellent stability, without any mechanical or electrical damage. The adhesion, proliferation, and differentiation of neural and muscle cells cultured on these hybrids are demonstrated, advancing the field of tissue engineering with integrated electronics.

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The arrival of a variety of new implants in the last two decades, together with the progress in surgical technique and postoperative care, has improved dramatically the performance of spine surgery. The problem that remains as yet is the poor bone quality in elderly patients. This reports attempts to describe current status and future prospect of spine reconstruction surgery and bone regeneration, especially in patients with osteoporosis.

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In spinal instrumentation for the treatment of vertebral fractures, it is common to loosen for screws which are inserted into vertebrae and strongly immobilized by a rigid rod. Therefore, we have been proposed an improved rod with a damper structure to increase freedom of movement of the rod and allow more flexible fixation of the spine. Because one of the factors of the occurrence of the loosening is decrease of fixity due to morphological change of trabecular bone by remodeling around screw, it is important to elucidate the relationship between the improved structure of rod and morphological change of bone around the screw. In this study, first, in order to identify loading condition of vertebral body for bone remodeling, we elucidated the relationship between morphological change in trabecular bone of vertebral body and tightening force by annulus fibrous using our remodeling simulation framework. Second, we performed remodeling simulation around the inserted screw in vertebral model to clarify relationship between trabecular morphology and apparent stiffness of the damper part of the proposed rod. As results, bone formation in the horizontal axis occurred more active as magnitude of the tightening force was stronger, suggesting that the tightening force strongly affected trabecular bone morphology by remodeling. In addition, number of trabecular bone around inserted screw kept high in remodeling process in the flexible fixation because mechanical stimulus was transferred to trabecular bone below the inserted screw, suggesting that the loosening risk of screw was low in the flexible fixation.

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Osteon, an anatomical unit of cortical bone, is a hollow cylindrical structure that is composed of multiple lamellae concentrically arranged around a haversian canal. The osteon is a porous material consisting of a bone matrix and interstitial fluid in a lacuno-canalicular porosity. The flow of interstitial fluid induced by deformation of the bone matrix is believed to play an important role in the mechanosensing by osteocytes. In order to identify the effects of variations in material properties resulting from the lamellar structure, we investigated the interstitial fluid flow in a single lamellar osteon subjected to cyclic loading based on poroelasticity, particularly focusing on variations in the permeability. The poroelastic analysis suggested that osteocytes buried in the neighborhood of the haversian canal are exposed to large flow stimuli when the permeability of the inner lamella is relatively larger than that of the outer lamella.

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Bone remodels its structure to functionally adapt to its mechanical environment. Bone cells produce signaling molecules activated by mechanical stimuli. It is considered that remodeling signals regulate bone remodeling. RANK, RANKL and OPG are well known as remodeling signals. RANKL promotes osteoclastogenesis by binding to RANK, while OPG acts as a decoy receptor by binding to RANKL. In this study, we proposed mathematical models of trabecular bone remodeling combining mechanosensing and remodeling signals, and conducted computational simulation. Focusing on the active bone remodeling area, we discussed the effects of remodeling signals on the functional adaptation capacity of trabeculae. We found that, under the condition where RANKL and OPG expressions balance each other, the active remodeling area is larger when both of the rates are higher.

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Porous HA scaffolds were fabricated by using the polyurethane sponge template method and varying the compressive ratio at 95%, 75% and 50%. Two phase composite scaffolds were then fabricated by introducing collagen (COL) sponge or COL sponge with HA particles into the HA scaffolds. The porous microstructure of fabricated biomaterials were characterized by FE-SEM and compression tests were performed to evaluate mechanical properties. It was revealed that the incorporation of COL or COL/HA materials into the pure HA scaffolds enhanced the mechanical properties significantly. Higher compressive rate corresponds to higher porosity, and therefore lower mechanical properties. By introducing COL or COL/HA secondary phase, the compressive properties were effectively improved. Relationships between the mechanical properties and the porosity were found to be approximated by quadratic functions.

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In the field of bone regenerative medicine, the need for artificial bone substitutes has been rapidly increasing, and various porous bioactive ceramics have been developed for use as bone substitutes. While materials such as β-tricalcium phosphate (β-TCP) have good oseteoconductivity, poly (L-lactide acid) (PLLA) has been shown to have good mechanical and physical properties. Therefore, the primary aim of this study was to fabricate a porous β-TCP scaffold with a PLLA network structure (β-TCP/PLLA) for use in bone tissue engineering. The fabricated β-TCP/PLLA scaffolds were characterized by their surface micro structures and compressive moduli. The results demonstrated that the structure of the PLLA membrane, such as pore size and thickness of membrane, could be changed by varying the concentration of PLLA.

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Calcined bone is attractive as scaffold material for tissue-engineered bones in biocompatibility and low manufacturing cost. However, its bioabsorbability is still unknown. The objective of this study is to investigate the effects of calcination temperature on the bioabsorbability of calcined bone. Bovine compact bones were calcined at 600 ℃ or 900 ℃ for 22 hours and immersed in the simulated body fluid (Ringer lactate solution) at 37 ℃. The bioabsorbability of calcined bone were evaluated by measuring calcium concentration in the simulated body fluid during incubation time up to 3 days. As a result, either calcined bone at 600 ℃ or 900 ℃ decreased calcium concentrations in the fluid. This tendency was more remarkable in the samples at 600 ℃. The result suggests that calcined bone is osteoconductive rather than bioabsorbable.

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New bone substitute material is demanded that has biocompatibility. Other, it is wished that the material is according to go time to decrease material. It was selected to use polybutylene succinate (PBS) -Hydroxyapatite (HAp) composite material. PBS has been a biodegradable resin and excellent ductility. HAp has been a bone formation inducing ability, which would been advance the reproduction of defected bones. However, there also have been our laboratory reports that the strength property of PBS-HAp composite material is lower than that of pure PBS material. Therefore, it is needed that has been kept two advantage while improving strength property. So, it is selected to use glass fiber (GF) for fiber reinforcement. The purpose is study investigate mechanical evaluation that New material design is prepared that has PBS-GF-HAp composite material. We performed the three-point bending test for the specimen to estimate the maximum bending strength and load stroke. As a result, it was recognized that PBS-GF-HAp composite material is obtained high bending strength and toughness by fiber reinforcement. Furthermore, composite material with continuous fiber is obtained higher bending strength than composite material with single fiber because continuous fiber has more bridging effect. Furthermore, PBS-GF composite material doesn't have fiber reinforcement because GF isn't obtained surface treatment by HAp.

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Bone graft materials with interconnected porous structure have paid much attention because the porous structure allows cells to penetrate into the bone grafts and may enhance its bone replacement. In this study, interconnected porous artificial bone grafts were fabricated by employing setting mechanism of brushite forming cement. Calcium carbonate or calcium phosphate granules with a few hundred micro meters in size were reacted with acidic calcium phosphate solution to obtain the bridging between the granules due to the precipitation of brushite crystals on the granular surface. In the case of granules containing carbonate ions such as calcium carbonate, external pressure to the piling of the granules in the mold was needed to close the granules each other during the reaction since a generation of CO_2 gas due to the reaction prevented the interlocking of precipitated brushite crystals at the interface between granules. Histological analysis obtained from rabbit's tibia with implanted porous specimens indicated that surrounding tissues can be penetrated into the interconnected porous structure and also new bone can be observed inside of the pores. Therefore, we concluded that the interconnected porous artificial bone grafts fabricated using granular binding method due to the precipitation of brushite is expected to be useful as an artificial bone substitute because of faster bone replacement due to the interconnected porous structure and the chemical composition.

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The main purpose of this study is the clarification of the effect of substrate elastic modulus on the metabolic behavior of osteoclasts on PCL substrates, and investigation of osteoclastic behavior of HAp/PCL substrates, aiming to extend the possibility to design the substrate elastic modulus. Here, PCL substrates with different elastic modulus were prepared by changing cooling method. The evaluated elastic modulus was 0.295 [GPa], 0.406 [GPa] and 0.657 [GPa] for rapid cooled, slow cooled and furnace cooled PCL substrates, respectively. HAp/PCL substrate with elastic modulus of 0.461 [GPa] was also prepared by rapid cooling. As results, the ratio of activated osteoclasts secreting cathepsin K increased with increasing elastic modulus of PCL substrates. In addition, it was suggested that osteoclasts can produce acid even on HAp/PCL substrates. It is expected that the effect of the composition with HAp on the osteoclastic metabolic behavior will be investigate parametrically, in future.

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Osteocytes are believed to act as mechanosensory cells in mechanically adaptive bone remodeling. The cell body of osteocytes has various morphology depending on the types of bone, surrounding mechanical environment and degree of maturation. The difference in osteocyte morphology can significantly affect the mechanosensitivity of the cells. In this study, we aim at identifying the relationship between the maturation and morphology of osteocytes within tissue by the morphometry of osteocytes based on technique of fluorescence imaging. Using a mouse femur, we labeled the newly formed bone by calcein to visualize the maturation stage of osteocytes. Furthermore, we fluorescently stained actin cytoskeleton in osteocytes and measured aspect ratio of individual cell body. As a result, calcein-labeled bone clearly showed the process of bone formation, therefore enabled us to estimate the degree of osteocyte maturation. The aspect ratio of the osteocytes cell body did not depend on the degree of maturation. This result suggested that the morphology of osteocytes can be influenced by the mechanical environment when they are buried in osteoid during the differentiation, rather than the degree of maturation.

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In this study, surface modification method using O_2 plasma-treated polydimethylsiloxane (PDMS) was developed to minimize the influences of fibroblast for bone formation. 3-well chambers consist of polycarbonate wall and glass slide coated with PDMS were prepared. Ultra-thin glass plates coated with PDMS were prepared to measure adhesive force between cell and PDMS surface. Contact angle of PDMS surface was controlled by O_2 plasma treatment (0°, 50° and 100°). Fibroblast and osteoblast-like cell were seeded respectively on the ultra-thin glass plate and 3-well chambers. Adhesive force was measured by detaching a cell from PDMS surface with micropipette and focal adhesion of vinculin was counted with fluorescent observation after 6 hours of cultivation The difference of adhesive force between osteoblast-like cell and fibroblast was highest on the PDMS surface with contact angle of 50°, and the difference of the number of focal adhesions was also highest on the surface. Co-culture of osteoblast-like cells and fibroblasts was carried out on the 3-well chambers. The ratio of osteoblast-like cell to fibroblast was 1:1. In the case of PDMS with contact angle of 50°, the number of adherent osteoblast-like cells was highest according to fluorescent observation after 6 hours of cultivation, and ALP activity was also highest after 9 days of cultivation. These results showed that PDMS surface with contact angle of 50° can maintain ALP activity of osteoblast-like cells with the influence of fibroblasts minimized for co-culture because the difference of cell adhesion between osteoblast-like cell and fibroblast was high on the contact angle.

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