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Printed electronics (PEs) have attracted attention for the fabrication of microscale electronic circuits. PEs use conductive inks which include metal nanoparticles. The conductive ink can be printed on flexible substrates for wearable devices using ink-jet printers and roll-to-roll methods. With the scaling down of electric devices, the current density and Joule heating in the device lines increase, and electromigration (EM) damage becomes significant. EM is a transportation phenomenon of metallic atoms caused by the electron wind under high-density current. Reducing the EM damage is extremely important to enhance the device reliability. With the progress in miniaturization of the metal nanoparticle ink lines, EM problem needs to be solved for ensuring the reliability of these lines. We know that the formation of aggregates and cathode damages occur due to a current loading. The diffusion path of atoms due to the EM has not been identified under the high-density current loading. In this study, a high-density electric current loading was applied to an Ag nanoparticle line. The line specimens were prepared using a lift-off method. After the current loading tests, observations were conducted using a laser microscope and scanning electron microscope. A local decrease in the line thickness and scale-shaped slit-like voids were observed due to the high-density current loading. Moreover, the microstructure of the line was modified by enlarging the Ag grain. From the results, we identified that a dominant diffusion occurred at the Ag grain boundary due to the EM.

Introduction: We devised a strategy for the fabrication of an ‘anatomy-mimicking’ cylinder-type engineered trachea combined with cartilage engineering. The engineered BIOTUBEs are used to support the architecture of the body tissue, for long-segment trachea (>5 cm) with carinal reconstruction. The aim of the present study was to fabricate an anatomy-mimicking cylinder-type regenerative airway, and investigate its applicability in a rabbit model. Methods: Collagen sponge rings (diameter: 6 mm) were arranged on a silicon tube (diameter: 6 mm) at 2-mm intervals. Chondrocytes from the auricular cartilage were seeded onto collagen sponges immediately prior to implantation in an autologous manner. These constructs were embedded in dorsal subcutaneous pouches of rabbits. One month after implantation, the constructs were retrieved for histological examination. In addition, cervical tracheal sleeve resection was performed, and these engineered constructs were implanted into defective airways through end-to-end anastomosis. Results: One month after implantation, the engineered constructs exhibited similar rigidity and flexibility to those observed with the native trachea. Through histological examination, the constructs showed an anatomy-mimicking tracheal architecture. In addition, the engineered constructs could be anastomosed to the native trachea without air leakage. Conclusion: The present study provides the possibility of generating anatomy-mimicking cylinder-type airways, termed BIO-AIR-TUBEs, that engineer cartilage in an in-vivo culture system. This approach involves the use of BIOTUBEs formed via in-body tissue architecture technology. Therefore, the BIO-AIR-TUBE may be useful as the basic architecture of artificial airways. Keywords: Anatomy-mimicking airway, Cylinder-type airway reconstruction, BIOTUBE, Engineered cartilage, BIO-AIR-TUBE

Cuprous oxide (Cu2O) is widely used in thin-film transistors as a p-type semiconductor material, and Cu2O nanowire studies have been actively conducted to enhance device performance and facilitate further scaling down. As scaling down progresses, the device line failure arising from electromigration becomes a constant challenge; however, the characteristics of Cu2O under high-density current have not yet been investigated. Hence, this study performed current loading tests on Cu2O specimens. Dumbbell shaped specimens were fabricated through Cu sputtering, photolithography, and thermal oxidation processes. The main component of the specimen was nanocrystalline Cu2O according to the x-ray diffraction measurement. The relatively high-potential drop specimen often failed at the middle region of the straight section during 1.0 MA/cm2 current loading. The middle-region failure was thought to be the result of the line degradation caused by Joule heating. In contrast, the relatively low-potential drop specimen often failed at the anode-side region because the cross-section area increased at the cathode and middle regions and decreased at the anode regions during current loading. In the usual electromigration phenomenon, atomic transport occurs from the cathode to the anode side; therefore, a lack of atoms can occur on the cathode side. Anode-side failures occurred likely because of the change of nanocrystalline Cu2O to coarse grained material at the middle region from Joule heating during current loading and the difference in atom transportability between the middle region and both end regions of the straight section of the specimen.

Flexible printed circuits (FPCs) are widely used in electronic equipment such as mobile devices and wearable sensors. The conductive electric lines in these circuits are printed using nanoparticle metal ink and ink-jet direct write methods. Physical characteristics such as flexibility and mechanical durability of metal nanoparticle ink lines have been evaluated by bending or tensile tests. In contrast, the electrical characteristics of these lines have not been sufficiently evaluated, and the failure mechanism under high-density current has not been clarified. When electric devices are scaled down, current density and Joule heating increase in conductive lines and electromigration (EM) damage becomes a severe problem. Therefore, reducing the EM damage is extremely important to enhance the device reliability. In this study, a failure analysis of Ag nanoparticle ink lines were assessed using current loading tests and microscopic observations to discuss the damage mechanism and evaluate electrical reliability under high-density current. Atomic transport due to EM was observed at 60 kA/cm2 current loading, and relatively large aggregates and grain growth were observed at 120 kA/cm2 current loading. The time to open circuit was longer at 120 kA/cm2 than at 60 kA/cm2. The formation of large aggregates and unstable changes in the potential drop were observed at the two values of current density. It is considered that aggregate formation and grain growth affected the atomic transport by EM.

Flexible printed circuits (FPCs) are widely used in electronic devices such as movable part line or wearable sensor. Photolithography is one of the most popular processes for fabricating electric interconnect lines. However, inkjet printing has attracted attention because the method can draw an arbitrary-shape electric lines without any mask. Therefore, nanoparticle metal ink is widely used for printing of conductive electric lines with lowering cost and small-lot production. The physical characteristics such as flexibility or durability of metal nanoparticle ink lines have been evaluated by bending or tensile tests. By contrast, the evaluation method has not been sufficiently established for the electrical characteristics of these lines, and the failure mechanism under high-current density has not been clarified. According to scaling down of electric devices, current density and Joule heating in device lines increase and electromigration (EM) damage becomes a serious problem. EM is a transportation phenomenon of metallic atoms caused by electron wind under high-current density. Reducing EM damage is extremely important to enhance device reliability. In this study, current loading tests of metal nanoparticle ink line were performed to discuss damage mechanism and evaluate electrical reliability under high-current density condition. As the results of current loading tests, the thickness of cathode part of straight-test line was decreased. It is considered that atomic transport from the cathode to the anode occurred by EM phenomenon. The line surface became rough and aggregates of particles generated at middle or anode parts of straight-test line by high-current loading. Both of atomic transport and aggregate generation were closely related the changes of potential drop, their dominances were varied depending the current density value.

The mechanical properties of fish are closely related to texture and are generally evaluated by macroscopic tests. During freezing storage, however, mechanical damage, such as the growth of ice crystals, occurs at the microscopic level. In this study, scanning haptic microscopy (SHM) measurements were performed on refrigerated and freeze–thaw tuna fillets to observe the microscopic elastic modulus distribution in food samples. In elastic images of the refrigerated samples, areas of hard myotome membrane and soft muscle were clearly discernible. For the muscle area, the elastic modulus of the freeze–thaw sample was significantly higher than that of the refrigerated sample, which was consistent with macroscopic indentation results. In contrast, there were no significant differences in the elastic modulus due to freezing in the myotome area. Thus, we propose that SHM imaging is useful for the evaluation of microscopic mechanical damage.

Reservoirs, extensions at the cathode-end, are constructed to extend the lifetime of integrated circuit (IC) lines in terms of electromigration (EM) damage. The threshold current density jth is the maximum current density that can be supported without causing EM damage due to the matching of the EM driving force and the back flow force, which is related to the atomic density gradient. In a previous study, we reported that reservoirs can affect jth. In this present study, the jth of straight Al polycrystalline lines covered with passivation was evaluated using a numerical simulation technique focusing not only on the formation of voids but also hillocks. The optimum reservoir/sink length based on ease of formation of voids and hillocks was discussed. The reservoir suppressed void formation but promoted hillock formation. Conversely, the sink suppressed hillock formation but promoted void formation. Therefore, when void and hillock formation occurred with equal case, it was considered that either no extension, or reservoir and sink of identical length were preferable for optimal threshold current density jth. Additionally, when considering the diffusivity of atoms depending on grain boundary direction, the absence of the extension represented the optimum condition because longer reservoirs/sinks produced smaller jth. When the ease of void and hillock formation changed, the critical atomic density of void and hillock formation shifted in response, causing the optimal extension length to change. It was found that the optimum extension length changed almost linearly based on the ease of void and hillock formation.

Biotubes, i.e., in vivo tissue-engineered connective tubular tissues, are known to be effective as vascular replacement grafts with a diameter greater than several millimeters. However, the performance of biotubes with smaller diameters is less clear. In this study, MicroBiotubes with diameters 1 mm were prepared, and their patency was evaluated noninvasively by optical coherence tomography (OCT) and magnetic resonance angiography (MRA). MicroBiotube molds, containing seven stainless wires (diameter 0.5 mm) covered with silicone tubes (outer diameter 0.6 mm) per mold, were embedded into the dorsal subcutaneous pouches of rats. After 2 months, the molds were harvested with the surrounding capsular tissues to obtain seven MicroBiotubes (internal diameter 0.59 ± 0.015 mm, burst pressure 4190 ± 1117 mmHg). Ten-mm-long MicroBiotubes were allogenically implanted into the femoral arteries of rats by end-to-end anastomosis. Cross-sectional OCT imaging demonstrated the patency of the MicroBiotubes immediately after implantation. In a 1-month follow-up MRA, high patency (83.3 %, n = 6) was observed without stenosis, aneurysmal dilation, or elongation. Native-like vascular structure was reconstructed with completely endothelialized luminal surfaces, mesh-like elastin fiber networks, regular circumferential orientation of collagen fibers, and α-SMA-positive cells. Although the long-term patency of MicroBiotubes still needs to be confirmed, they may be useful as an alternative ultra-small-caliber vascular substitute.

Single-point measurement methods have been proposed to study both microscopic to macroscopic adhesive properties; however, thus far, a simple and quantitative distribution observation method has not been established. A scanning haptic microscope (SHM) was developed to observe microscopic distribution of the elastic modulus of biological tissue surfaces. The SHM comprises a vibrating glass probe and measures the elastic modulus from the variation in vibration frequency during indentation by the probe. By focusing on the variation in frequency during the pulling of the probe, the adhesive properties between sample surface and probe tip could be evaluated. In this study, we examined the possibility of measuring adhesion properties, as a basis study of adhesive property mapping by SHM. The samples used were silicone gels with different adhesive properties by varying the mixing ratio of silicones with high or low adhesion. The sample was indented using a glass probe as in usual SHM measurements. The time difference during the variation in frequency between indentation and pulling (i.e., adhesion time) of each silicon sample was clearly distinguished. The adhesion time measured by the SHM was closely related to tack indices in rolling ball and probe tack tests; classical tests were conducted to quantitatively evaluate the tack. SHM is expected to be a powerful mapping tool of adhesive property with microscopic spatial resolution for centimeter-level measurement areas.

The treatment of large or wide-necked cerebral aneurysms is extremely difficult, and carries a high risk of rupture, even when surgical or endovascular methods are available. We are developing novel honeycomb microporous covered stents for treating such aneurysms. In this study, 3 experimental animal models were designed and evaluated quantitatively before preclinical study. The stents were prepared using specially designed balloon-expandable stents (diameter 3.5-5.0 mm, length 16-28 mm) by dip-coating to completely cover their struts with polyurethane film (thickness 20 µm) and microprocessing to form the honeycomb pattern after expansion. (1) In an internal carotid artery canine model (n = 4), all stents mounted on the delivery catheter passed smoothly through the tortuous vessel with minimal arterial damage. (2) In an the large, wide-necked, outer-sidewall aneurysm canine model, almost all parts of the aneurysms had embolized immediately after stenting (n = 4), and histological examination at 2 months revealed neointimal formation with complete endothelialization at all stented segments and entirely organized aneurysms. (3) In a perforating artery rabbit model, all lumbar arteries remained patent (n = 3), with minimal change in the vascular flow pattern for over 1 year, even after placement of a second, overlapping stent (n = 3). At 2 months after stenting, the luminal surface was covered with complete thin neointimal formation. Excellent embolization performance of the honeycomb microporous covered stents without disturbing branching flow was confirmed at the aneurysms in this proof-of-concept study.

Small-diameter biotube vascular grafts developed by in-body tissue architecture had high patency at implantation into rabbit carotid arteries or rat abdominal aortas. However, the thin walls (34 ± 14 μm) of the original biotubes made their implantation difficult into areas with low blood flow volumes or low blood pressure due to insufficient mechanical strength to maintain luminal shape. In this study, caged molds with several windows were designed to prepare more robust biotubes. The molds were assembled with silicone tubes (external diameter 2 mm) and cylindrical covers (outer diameter 7 mm) with 12 linear windows (1 × 9 mm). After the molds were embedded into beagle dorsal subcutaneous pouches for 4 weeks, type C (cage) biotubes were obtained by completely extracting the surrounding connective tissues from the molds and removing the molds. The biotube walls (778 ± 31 μm) were formed at the aperture (width 1 mm) between the silicone rods and the covers by connective cell migration through the windows of the covers. Excellent mechanical properties (external pressure resistance, approximately 4 times higher than beagle native femoral arteries; burst strength, approximately 2 times higher than original biotubes) were obtained. In the acute phase of implantation of the biotubes into beagle femoral arteries, perfect patency was obtained with little stenosis and no aneurysmal dilation. The type C biotubes may be useful for implantation into peripheral arteries or veins in addition to aortas.

In autologous valved conduits (biovalves) using in-body tissue architecture, the limited area available for leaflet formation is a concern. In this study, we designed a novel biovalve mold with slits to enhance in vivo cell migration, regardless of size. As a control, the original mold without slits was used. When both types of molds were embedded into subcutaneous pouches in beagle dogs for 8 weeks, the outer surfaces of all molds were completely covered with connective tissue to form conduit tissue. In the molds without slits, the leaflet size was limited to half of the design. In contrast, in the mold with slits, the complete leaflet area was formed. Upon trimming excess peripheral tissues, removing the mold, and cutting the connective tissue formed at the slits, completely autologous connective tissue biovalves with the designed leaflet area were obtained as type S (diameter, 6-28 mm) biovalves. The slit structure customized to the mold was effective for allowing cells to enter, thereby facilitating cell migration and contributing to the successful preparation of reliable biovalves of various physiological sizes suitable for all clinical uses.

We developed an autologous, trileaflet tissue valve ("biovalve") using in-body tissue architecture technology to overcome the disadvantages of current bioprosthetic valves. We designed a novel biovalve with a balloon-expandable stent: the stent biovalve (SBV). This study evaluated the technical feasibility of sutureless aortic valve replacement using the SBV in an orthotopic position, as well as the functionality of the SBV under systemic circulation, in an acute experimental goat model. Three adult goats (54.5-56.1 kg) underwent sutureless AVR under cardiopulmonary bypass (CPB). The technical feasibility and functionality of the SBVs were assessed using angiography, pressure catheterization, and two-dimensional echocardiography. The sutureless AVR was successful in all goats, and all animals could be weaned off CPB. The mean aortic cross-clamp time was 45 min. Angiogram, after weaning the animals off CPB, showed less than mild paravalvular leakage and central leakage was not detected in any of the goats. The mean peak-to-peak pressure gradient was 6.3 ± 5.0 mmHg. Epicardial two-dimensional echocardiograms showed smooth leaflet movement, including adequate closed positions with good coaptation; the open position demonstrated a large orifice area (average aortic valve area 2.4 ± 0.1 cm2). Sutureless AVR, using SBVs, was feasible in a goat model. The early valvular functionalities of the SBV were sufficient; future long-term experiments are needed to evaluate its durability and histological regeneration potential.

Reservoir structures are often constructed in the interconnection to prevent the electromigration damages. In this study, a numerical simulation technique for analyzing the atomic density distributions in the line under high current density was used to evaluate the effects of reservoir length and location on the threshold current density considering void and hillock generations. The threshold current density is determined when the local atomic density in the line reaches the upper critical value for hillock creation or the lower critical value for void generation. Atomic density distributions in the line were simulated when cathode and anode reservoir lengths were changed. The threshold current density considering void formation became higher with longer cathode reservoir and shorter anode reservoir. However, opposite results obtained in the case of hillock formation. It was found that there was an optimum value of reservoir length, corresponding to both critical values of hillock and void initiation.

The use of stent grafts for endovascular aortic repair has become an important treatment option for aortic aneurysms requiring surgery. This treatment has achieved excellent outcomes; however, problems like type 1 endoleaks and stent graft migration remain. Bio stent grafts (BSGs), which are self-expanding stents covered with connective tissue, were previously developed using "in-body tissue architecture" technology. We assessed their early adaptation to the aorta after transcatheter implantation in a beagle model. BSGs were prepared by subcutaneous embedding of acryl rods mounted with self-expanding nitinol stents in three beagles for 4 weeks (n = 3/dog). The BSGs were implanted as allografts into infrarenal abdominal aortas via the femoral artery of three other beagles. After 1 month of implantation, aortography revealed no stenosis or aneurysmal changes. The luminal surface of the BSGs was completely covered with neointimal tissue, including endothelialization, without any thrombus formation. The cover tissue could fuse the luminal surface of the native aorta with tight conjunctions even at both ends of the stents, resulting in complete impregnation of the strut into the reconstructed vascular wall, which is expected to prevent endoleaks and migration in clinical applications.

In this study, we aimed to describe the development of tissue-engineered self-expandable aortic stent grafts (Bio stent graft) using in-body tissue architecture technology in beagles and to determine its mechanical and histological properties. The preparation mold was assembled by insertion of an acryl rod (outer diameter, 8.6 mm; length, 40 mm) into a self-expanding nitinol stent (internal diameter, 9.0 mm; length, 35 mm). The molds (n = 6) were embedded into the subcutaneous pouches of three beagles for 4 weeks. After harvesting and removing each rod, the excessive fragile tissue connected around the molds was trimmed, and thus tubular autologous connective tissues with the stent were obtained for use as Bio stent grafts (outer diameter, approximately 9.3 mm in all molds). The stent strut was completely surrounded by the dense collagenous membrane (thickness, ∼150 µm). The Bio stent graft luminal surface was extremely flat and smooth. The graft wall of the Bio stent graft possessed an elastic modulus that was almost two times higher than that of the native beagle abdominal aorta. This Bio stent graft is expected to exhibit excellent biocompatibility after being implanted in the aorta, which may reduce the risk of type 1 endoleaks or migration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 381–386, 2015.

We designed a novel method for constructing an autologous heart valve with a stent, called a stent-biovalve. In constructing completely autologous heart valves, named biovalves, which used in-body tissue architecture technology, tissues for leaflets were formed via ingrowths into narrow apertures in the preparation molds, frequently leading to delayed or incomplete biovalve preparation. In this technique, self-expandable nitinol stents after everting were mounted on an acrylic column-shaped part and partially covered with an acrylic cylinder-shaped part with three slits. This assembled mold was placed into subcutaneous abdominal pouches in beagles or goats for 4 weeks. Upon removing the acrylic parts after harvesting and trimming of capsulated tissues, a tubular hollow structure with three pocket-flaps of membranous tissue rigidly fixed to the stent's outer surface was obtained. Then, the stent was turned inside out to the original form, thus moving the pocket-flaps from outside to the inside. Stent-biovalves with a sufficient coaptation area were thus obtained with little tissue damage in all cases. The valve opened smoothly, and high aperture ratio was noted. This novel technique was thus highly effective in constructing a robust, completely autologous stent-biovalve with adequate valve function.

Cu2O shows p-type semiconductor characteristics, have been investigated intensively for applications to opto-electronic devices and thin-film transistors (TFTs). Cu2O film is built by sputtering or pulsed laser deposition technique. Thermal oxidation of Cu can also create Cu2O layer, the resistivity (depending on the degree of oxidation) of the layer is controlled by temperature of heat treatment. Recently, studies on high integration such as fabrication of Cu2O nanowires were performed, but high current density due to scaling down of electronic devices induces electromigration (EM) damages. EM is a phenomenon that atom’s transport in the line by electron wind. In general, EM is one of key reasons for the failure of metal lines in electronic devices. Recently, EM failure of p-type semiconductor made of poly-crystalline silicon nanowires was studied. In this study, we conducted acceleration tests of micro-sized line of copper oxide which had p-type semiconductor characteristics to reveal electric characteristics under high current density. Straight-shaped copper oxide line samples were created on silicon substrates. Briefly, oxidation (SiO2) layer was grown on silicon substrate by thermal treatment (1173K, overnight). Cu layer with ca. 650 nm thickness was deposited on the SiO2 layer by sputtering. Cu line was fabricated through photolithography and wet-etching process. Width and length of straight test section of the line were ca. 20 um and 460 um, respectively. The Cu line was oxidized by thermal treatment (473K, 5 min). The resistivity of the copper oxide film prepared under the same conditions was 10-5 order [Ωm]. In energy dispersive X-ray spectroscopy (EDX), the O/Cu ratio of the thermal treated Cu layer was higher than that of before thermal treated. Also, the resistance of obtained copper oxide line decreased according to increasing of ambient temperature (303 to 373 K). It was considerable that the obtained copper oxide line was semiconductor materials with main component of Cu2O. Acceleration electric failure test was performed to the obtained electric lines. The sample was heated to 373K by using ceramic plate heater. Constant current (1.0 MA/cm2) applied to the obtained line by using constant current power supply and galvanometer. As shown in Fig (a), sample 1 with relatively high electric resistance was broken near the center of the test section at relatively short time (several tens minute). It seems that Joule heating was the key factor of failure, and the sample line broke at the center part with high temperature. By contrast, sample 2 with relatively low electric resistance broke near the anode side in test section at relative long time (several hundreds minute), as shown in Fig (b). In the laser microscope observations, the cross-sectional area of sample 2 was increased at the cathode side and decreased at the anode side. There is a possibility that the atomic transport due to EM was affected the failure at sample 2. In general, EM failure of metal line was observed at cathode side, since atomic transport occurred from cathode to anode with electron transport. It was reported that the semiconductor line made of poly-crystalline silicon nanowires was broken at the anode side. The failure at anode side was guessed that regrowth of grain was occurred due to Joule heating, they called this phenomenon thermally-assisted electromigration. It was suggested that similar EM failure occurred in sample 2. Acceleration electric failure tests of dumbbell-shaped copper oxide lines were performed, and failure at the anode side was observed. There is a possibility that the failure is related to thermally-assisted electromigration. It is expected that more detailed mechanism of this phenomenon can be demonstrated by the failure tests using various oxidized samples. Figure 1

Background: We developed covered stents with a microhoneycomb mesh for the treatment of large or giant wide-necked cerebral aneurysms. These aneurysms are extremely difficult to treat and carry high risks, even with the use of clinically available surgical methods or the endovascular technique using coils with the assistance of bare stents. This preclinical study confirmed the excellent performance of our stents in three animal experimental models. Methods and Results: The covered stents were prepared by using balloon-expandable stents (CoCr; diameter, 3.5-5.0 mm; length, 16-28 mm) and by dip coating to cover their struts completely with a polyurethane membrane (thickness, 20 μm), followed by laser microprocessing (pore size, approximately 100 μm; opening ratio, approximately 30%). Model 1: In prepared tortuous canine arteries (n = 12) that simulated the shape of the human internal carotid artery, all stent-mounted delivery catheters could smoothly navigate with little arterial damage. Model 2: In a prepared canine model (n = 10) of large (over 7 mm), wide-necked (over 4 mm) outer-sidewall aneurysms, at 3 months after stenting, completely endothelialized neointima was formed at the aneurysm openings and the aneurysm sacs were entirely organized. Model 3: In rabbit branching abdominal aortas, the vascular flow pattern at all the branching arteries remained unchanged for over 1 year, even after performing overlap stenting (n = 5) in addition to single stenting (n = 5). On all the stented luminal surfaces, complete thin neointimal formation with complete endothelialization was observed. Conclusion: Our newly developed novel covered stents exhibited excellent preclinical performance in three animal experimental models in terms of stent delivery, aneurysm embolization, and flow maintenance in branching arteries. We highly expect that the stents will be useful as endovascular embolization devices for large and wide-necked aneurysms in humans.

Biotubes, i.e., in vivo tissue-engineered connective tubular tissues, are known to be effective as vascular replacement grafts with a diameter greater than several millimeters. However, the performance of biotubes with smaller diameters is less clear. In this study, MicroBiotubes with diameters