Ōsaka, Japan
Ōsaka, Japan

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Funayama M.,Japan National Cardiovascular Center Research Institute | Funayama M.,Nihon University | Takewa Y.,Japan National Cardiovascular Center Research Institute | Oie T.,Japan National Cardiovascular Center Research Institute | And 4 more authors.
Journal of Artificial Organs | Year: 2015

Biovalves, autologous tri-leaflet valved conduits, are formed in the subcutaneous spaces of animals. The valves are formed using molds encapsulated with autologous connective tissues. However, tissue migration into the small apertures in the molds for leaflet formation is generally slower than that for conduit formation around the molds. In this study, the formation of the leaflet tissues was directly and non-invasively observed using a wireless capsule endoscope. The molds were assembled from 6 parts, one of which was impregnated with the endoscope, and embedded into subcutaneous pouches in goats (n = 30). Tissue ingrowth into the apertures gradually occurred from the edges of the leaflet parts. Tissue formation was accompanied by capillary formation. At 63.1 ± 17.1 days after embedding, the apertures were completely replaced with autologous connective tissue, forming the leaflet tissues. Leaflet formation was enhanced by including fat tissue (46.7 ± 4.2 days) or blood (41.1 ± 6.9 days) in the apertures before embedding. The creation of slit openings, in conjunction with addition of blood to the apertures, further enhanced leaflet formation (37.0 ± 2.8 days). Since leaflet formation could be observed endoscopically, the appropriate embedding period for complete biovalve formation could be determined. © 2014, The Japanese Society for Artificial Organs.


Moriwaki T.,Japan National Cardiovascular Center Research Institute | Moriwaki T.,Hokkaido University | Oie T.,Japan National Cardiovascular Center Research Institute | Oie T.,Shinkan Kogyo Co. | And 7 more authors.
Journal of Artificial Organs | Year: 2011

Variations in microscopic elastic structures along the entire length of canine aorta were evaluated by use of a scanning haptic microscope (SHM). The total aorta from the aortic arch to the abdominal aorta was divided into 6 approximately equal segments. After embedding the aorta in agar, it was cut into horizontal circumferential segments to obtain disk-like agar portions containing ring-like samples of aorta with flat surfaces (thickness, approximately 1 mm). The elastic modulus and topography of the samples under no-load conditions were simultaneously measured along the entire thickness of the wall by SHM by using a probe with a diameter of 5 μm and a spatial resolution of 2 μm at a rate of 0.3 s/point. The elastic modulus of the wall was the highest on the side of the luminal surface and decreased gradually toward the adventitial side. This tendency was similar to that of the change in the elastin fiber content. During the evaluation of the mid-portion of each tunica media segment, the highest elastic modulus (40.8 ± 3.5 kPa) was identified at the thoracic section of the aorta that had the highest density of elastic fibers. Under no-load conditions, portions of the aorta with high elastin density have a high elastic modulus. © 2011 The Japanese Society for Artificial Organs.


Takewa Y.,Japan National Cardiovascular Center Research Institute | Yamanami M.,Japan National Cardiovascular Center Research Institute | Yamanami M.,Kyoto Prefectural University of Medicine | Kishimoto Y.,Japan National Cardiovascular Center Research Institute | And 13 more authors.
Journal of Artificial Organs | Year: 2013

Using simple, safe, and economical in-body tissue engineering, autologous valved conduits (biovalves) with the sinus of Valsalva and without any artificial support materials were developed in animal recipients' bodies. In this study, the feasibility of the biovalve as an aortic valve was evaluated in a goat model. Biovalves were prepared by 2-month embedding of the molds, assembled using two types of specially designed plastic rods, in the dorsal subcutaneous spaces of goats. One rod had three projections, resembling the protrusions of the sinus of Valsalva. Completely autologous connective tissue biovalves (type VI) with three leaflets in the inner side of the conduit with the sinus of Valsalva were obtained after removing the molds from both terminals of the harvested implants with complete encapsulation. The biovalve leaflets had appropriate strength and elastic characteristics similar to those of native aortic valves; thus, a robust conduit was formed. Tight valvular coaptation and a sufficient open orifice area were observed in vitro. Biovalves (n = 3) were implanted in the specially designed apico-aortic bypass for 2 months as a pilot study. Postoperative echocardiography showed smooth movement of the leaflets with little regurgitation under systemic circulation (2.6 ± 1.1 l/min). α-SMA-positive cells appeared significantly with rich angiogenesis in the conduit and expanded toward the leaflet tip. At the sinus portions, marked elastic fibers were formed. The luminal surface was covered with thin pseudointima without thrombus formation. Completely autologous biovalves with robust and elastic characteristics satisfied the higher requirements of the systemic circulation in goats for 2 months with the potential for valvular tissue regeneration. © 2012 The Japanese Society for Artificial Organs.


Oie T.,Japan National Cardiovascular Center Research Institute | Oie T.,Hokkaido University | Oie T.,Shinkan Kogyo Co. | Suzuki H.,Japan National Cardiovascular Center Research Institute | And 8 more authors.
Journal of Artificial Organs | Year: 2010

The objective of this study was to make anelasticity distribution image of natural arteries in a liquid environment at high resolution at the micrometer level and at a wide area at the sub-square millimeter level by improving the scanning haptic microscope (SHM), developed previously for characterization of the stiffness of natural tissues. The circumferential sections (thickness, 1.0 mm) of small-caliber porcine arteries (approximately 3-mm diameter) were used as a sample. Measurement was performed by soaking a probe (diameter, 5 μm; spatial resolution, less than 2 μm) in saline solution at an appropriate depth. The vascular tissues were segregated by multi-layering a high elasticity region with mainly elastin (50.8 ± 13.8 kPa) and a low one with mainly collagen and smooth muscle cells (17.0 ± 9.0 kPa), as observed previously in high humidity conditions. The elasticity was measured repeatedly with little change for over 4 h in a liquid environment, which enabled observation with maintenance of high precision of a large area of at least 1,200 × 100 μm, whereas the elasticity was increased with time by the dehydration of samples with shrinkage in the air, in which an averaged elasticity in the overall area was approximately doubled within 2 h. This simple, inexpensive system allows observation of the distribution of the surface elasticity at the extracellular matrix level of vascular tissues in a liquid environment close to the natural one. © 2010 The Japanese Society for Artificial Organs.


Oie T.,Osaka National Research Institute | Oie T.,Shinkan Kogyo Co. | Yamanami M.,Osaka National Research Institute | Yamanami M.,Kyoto Prefectural University of Medicine | And 4 more authors.
Journal of Artificial Organs | Year: 2010

The autologous biotube, developed by using in-body tissue architecture technology, is one of the most promising small-diameter vascular grafts in regenerative medicine. The walls of the biotubes obtained by a traditional silicone mold-based method were very thin, and this is still the primary obstacle while handling anastomosis, even though these biotubes have adequate pressure resistance ability. This pilot study showed the effect of optical stimulation of subcutaneous tissue formation in the body during the preparation of the biotubes. A blue light-emitting diode (LED) was embedded into a silicone rod as a mold. The biotube was prepared by placing the luminescent molds into the dorsal subcutaneous pouches of a pair of beagles (each weighing ∼10 kg) for 2 weeks under photoirradiation. The wall thickness of the obtained biotubes was 506.9 ± 185.7 μm, which was remarkably more than that of the previous biotubes prepared by 2 months of embedding similarly in beagles' subcutaneous pouches (thickness, 77.2 ± 14.8 μm). Many capillaries with smooth muscle cells were infiltrated into the wall and concentrated in the internal layer. Interestingly, the formation of elastic fibers had already started along with collagen fibers, mostly with a regular circumferential orientation. The short-term in-body optical stimulation resulted in the rapid formation of a biotube. These phenomena will allow easy surgical handling and may induce vascular maturation in histology during the acute phase after implantation. © 2010 The Japanese Society for Artificial Organs.

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