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ABSTRACT: We developed autologous vascular grafts, called "biotubes," by simple and safe in-body tissue architecture technology, which is a practical concept of regenerative medicine, without using special sterile conditions or complicated in vitro cell treatment processes. In this study, biotubes of extremely small caliber were first auto-implanted to rat abdominal aortas. Biotubes were prepared by placing silicone rods (outer diameter 1.5 mm, length 30 mm) used as a mold into dorsal subcutaneous pouches in rats for 4 weeks. After argatroban coating, the obtained biotubes were auto-implanted to abdominal aortas (n = 6) by end-to-end anastomosis using a custom-designed sutureless vascular connecting system under microscopic guidance. Graft status was evaluated by contrast-free time-of-flight magnetic resonance angiography (TOF-MRA). All grafts were harvested at 12 weeks after implantation. The patency rate was 66.7 % (4/6). MRA showed little stenosis and no aneurysmal dilation in all biotubes. The original biotube had wall thickness of about 56.2 ± 26.5 μm at the middle portion and mainly random and sparse collagen fibers and fibroblasts. After implantation, the wall thickness was 235.8 ± 24.8 μm. In addition, native-like vascular structure was regenerated, which included (1) a completely endothelialized luminal surface, (2) a mesh-like elastin fiber network, and (3) regular circumferential orientation of collagen fibers and α-SMA positive cells. Biotubes could be used as small-caliber vascular prostheses that greatly facilitate the healing process and exhibit excellent biocompatibility in vascular regenerative medicine.
Journal of Artificial Organs 11/2012; · 1.59 Impact Factor
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Yasuhide Nakayama,
Saori Yamaoka,
Masashi Yamanami,
Megumi Fujiwara,
Masami Uechi,
Keiichi Takamizawa,
Hatsue Ishibashi-Ueda,
Marie Nakamichi,
Kingo Uchida, Taiji Watanabe,
Keiichi Kanda,
Hitoshi Yaku
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ABSTRACT: Argatroban is a powerful synthetic anticoagulant, but due to its water-insoluble nature, it is unsuitable for use as a coating material to reduce the thrombogenic potential of natural or tissue-engineered blood-contacting cardiovascular tissues. On the other hand, anionic compounds could adsorb firmly onto connective tissues. Therefore, in this study, an anionic form of argatroban was prepared by neutralization from its alkaline solution, dialysis, and freeze-drying. The subsequently obtained argatroban derivative could be easily dissolved in water. Analysis of the surface chemical composition showed that the water-soluble argatroban (WSA) could be adsorbed on the entire surface of tissue-engineered connective tissue sheets composed mainly of collagen. Adsorption was achieved on immersion of the tissue-engineered connective tissue sheet in a saline/WSA solution for only 30 s without any change in the mechanical properties of the tissue-engineered sheets. Complete surface adsorption (ca., 1 mg/cm(2) ) was obtained at WSA concentrations of over 5 mg/mL. WSA adsorption was maintained for at least 7 days with rinsing. Blood coagulation was significantly prevented on the WSA-adsorbed surfaces in acute in vitro experiments. The coating was applied to in vivo tissue-engineered vascular grafts (biotubes) or tri-leaflet tissues (biovalves) under development, ensuring a high likelihood of nonthrombogenicity of their blood-contacting surfaces with high patency, at least in the subchronic phase. It appears that WSA satisfies the initial requirements for a biocompatible aqueous coating material for use in natural or tissue-engineered tissues.
Journal of Biomedical Materials Research Part B Applied Biomaterials 09/2011; 99(2):420-30. · 2.15 Impact Factor
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ABSTRACT: A mold for the preparation of an in-body tissue architecture-induced autologous vascular graft, termed "biotube," was prepared by covering a main silicone rod (outer diameter, 3 mm; length, 30 mm) with two pieces of polyurethane sponge tubes (internal diameter, 3 mm; length, 3 mm) at both ends. The molds were embedded into the dorsal subcutaneous pouch of rabbits (weighing ca. 2 kg) for 2 months. After harvesting the rods with the formed surrounding tissues, the rods were removed to create biotubes impregnated with anastomotic reinforcement cuffs at both ends. The biotubes had homogeneous, thin connective tissue wall (thickness, 76 ± 37 μm) that was primarily composed of collagen and fibroblasts. One biotube was loaded with argatroban and autoimplanted in the carotid artery for 26 months. Neither antiplatelet nor anticoagulant agents were administered, except for an intraoperative heparin injection. Follow-up angiography showed no aneurysm formation, rupturing, or stenosis during implantation. At the end of implantation, the wall thickness of biotube (212 ± 24 μm at the anastomosis portion and 150 ± 14 μm at the midportion) was similar to that of native artery (189 ± 23 μm). The luminal surface was completely covered with endothelial cells on the formed lamina elastica interna-like layer. The regenerated vascular walls comprised multilayered smooth muscle cells and dense collagen fibers with regular circumferential orientation. A remarkable multilayered elastin fiber network was observed near the anastomosis portion. Biotubes could thus be used as small-caliber vascular prostheses that greatly facilitate the healing process and exhibit excellent biocompatibility.
Journal of Biomedical Materials Research Part B Applied Biomaterials 07/2011; 98(1):120-6. · 2.15 Impact Factor
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Masashi Yamanami,
Yuki Yahata,
Masami Uechi,
Megumi Fujiwara,
Hatsue Ishibashi-Ueda,
Keiichi Kanda, Taiji Watanabe,
Tsutomu Tajikawa,
Kenkichi Ohba,
Hitoshi Yaku,
Yasuhide Nakayama
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ABSTRACT: We developed autologous prosthetic implants by simple and safe in-body tissue architecture technology. We present the first report on the development of autologous valved conduit with the sinus of Valsalva (BIOVALVE) by using this unique technology and its subsequent implantation in the pulmonary valves in a beagle model.
A mold of BIOVALVE organization was assembled using 2 types of specially designed silicone rods with a small aperture in a trileaflet shape between them. The concave rods had 3 projections that resembled the protrusions of the sinus of Valsalva. The molds were placed in the dorsal subcutaneous spaces of beagle dogs for 4 weeks. The molds were covered with autologous connective tissues. BIOVALVEs with 3 leaflets in the inner side of the conduit with the sinus of Valsalva were obtained after removing the molds. These valves had adequate burst strength, similar to that of native valves. Tight valvular coaptation and sufficient open orifice area were observed in vitro. These BIOVALVEs were implanted to the main pulmonary arteries as allogenic conduit valves (n=3). Postoperative echocardiography demonstrated smooth movement of the leaflets with trivial regurgitation. Histological examination of specimens obtained at 84 days showed that the surface of the leaflet was covered by endothelial cells and neointima, including an elastin fiber network, and was formed at the anastomosis sides on the luminal surface of the conduit.
We developed the first completely autologous BIOVALVE and successfully implanted these BIOVALVEs in a beagle model in a pilot study.
Circulation 09/2010; 122(11 Suppl):S100-6. · 14.74 Impact Factor
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ABSTRACT: A novel autologous valved conduit with the sinus of Valsalva-defined as a type IV biovalve-was created in rabbits by "in-body tissue-architecture" technology with a specially designed mold for the valve leaflets and the sinus of Valsalva and a microporous tubular scaffold for the conduit. The mold included 2 rods composed of silicone substrates. One was concave shaped, with 3 projections resembling the sinus of Valsalva; the other was convex shaped. The connection between the rods was designed to resemble the closed form of a trileaflet valve. The 2 rods were connected with a small aperture of 500-800 microm, which bound membranous connective tissue obtained from the dorsal subcutaneous layer of a rabbit. The rods were placed in a polyurethane scaffold that had many windows in its center. Both ends of the scaffold were tied with thread for fixation, and this assembly was embedded for 1 month in a subcutaneous pouch in the same Japanese white rabbit from which the connective tissue was obtained. After 1 month, all the surfaces of the implant were found to be completely covered with newly developed connective tissue. The substrates were removed from both sides of the harvested cylindrical implant, and homogenous well-balanced trileaflet-shaped membranous tissue was found inside the developed conduit with 3 protrusions resembling the sinus of Valsalva. The trileaflet valve closed and opened rapidly in synchrony with the backward and forward flow of a pulsatile flow circuit in vitro.
Journal of Artificial Organs 03/2010; 13(2):106-12. · 1.59 Impact Factor
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ABSTRACT: Functional autologous tubular tissues, termed "biotubes," have been developed as small-caliber vascular grafts. Biotubes can be easily and safely constructed in vivo by using a novel concept in regenerative medicine-in body tissue architecture technology, which requires neither clean specialized laboratories nor complex cell management. Biotubes with "anastomotic reinforcement cuffs" were prepared by embedding a silicone rod (diameter, 3 mm; length, 30 mm) as a mold in the dorsal subcutaneous pouches of rabbits. The rod was covered at both ends with 2 pieces of polyurethane sponge tubes (length, 3 mm), and it was removed when the grafts were harvested. These biotubes had homogeneous thin connective tissue walls (thickness: 76 +/- 37 microm) that were primarily composed of collagen and fibroblasts. The resulting cuff-impregnated biotubes were auto-implanted in the carotid arteries for predetermined periods of up to 12 weeks and then morphologically examined. On implantation of the biotubes after argatroban loading, the total patency was 9/11 without any instance of aneurysm formation or rupture. At 12 weeks after implantation, no significant neointimal thickening was observed (170 +/- 30 microm). In addition, minimal thrombus formation was observed on the luminal surfaces, which were completely covered with endothelial cells regularly oriented longitudinally. The regenerated vascular walls comprised multilayered smooth muscle cells and dense collagen fibers with regular circumferential orientation with few elastin fibers and were similar to native arteries. Biotubes with argatroban loading could thus be used as small-caliber vascular prostheses that greatly facilitate healing process and exhibit excellent biocompatibility.
Journal of Biomedical Materials Research Part B Applied Biomaterials 11/2009; 92(1):236-42. · 2.15 Impact Factor
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ABSTRACT: In the development of small-caliber vascular grafts (diameter; less than 3 mm), animal implantation studies have been mostly performed by using rat abdominal aortas, and their certain patency must evaluate with sacrificing every observation periods, which is both labor-intensive and time-consuming when performing a large number of experiments. This study is the first to demonstrate the application of 3-Tesla contrast-free time-of-flight magnetic resonance angiography (TOF-MRA) in the continuous assessment of the status of a tissue-engineered vascular graft in rat. As a model graft, a single connective tubular tissue (diameter; 1.5 mm), prepared by embedding the silicone rod (diameter; 1.5 mm) into a subcutaneous pouch of a rat for 2 weeks an in vivo tissue-engineering, was used. The graft was implanted in the abdominal aorta (diameter; 1.3 mm) of the rat by end-to-end anastomosis. Repeated TOF-MRA imaging of the graft obtained over a 3-month follow-up period after implantation made it possible to evaluate the patency of the graft, both simply and noninvasively. It also permitted visualization of the connected abdominal aorta and renal and common iliac arteries having smaller caliber (diameter; less than 1 mm). In addition, the degree of the stenosis or aneurysm could also be detected. 3-Tesla MRA allowed the simplified and noninvasive assessment of the status on the vascular graft, including the formation of a stenosis or aneurysm, in the same rat at different times, which will be contributing to enhance the development of tissue-engineered vascular grafts even with small caliber.
Journal of Biomedical Materials Research Part B Applied Biomaterials 10/2009; 92(1):156-60. · 2.15 Impact Factor
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ABSTRACT: The aim of this study was to prepare completely autologous heart-valve-shaped constructs without using any artificial scaffold materials by in-body tissue architecture technology, which is a practical concept of regenerative medicine based on the biological defense mechanism against foreign bodies. Silicone rods were used as molds to achieve the tubular shape of the arteries, which were implanted in the subcutaneous spaces of rabbits. After 2 weeks of primary in-body tissue incubation, the silicone rods were completely encapsulated within a thin membranous connective tissue mainly consisting of collagen and having a thickness of approximately 100 microm. To achieve the trileaflet shape of the valve, the cylindrical tissues obtained were rolled up with polyurethane belts cut in the shape of three semi-ovals. The assembled tissues were reimplanted for 2 weeks for secondary incubation. The resulting tissues were over-encapsulated with the newly developed membranous connective tissue having a thickness of approximately 200-400 microm. The newly formed membranes were completely fused to the previously developed inner membrane. After the removal of the two artificial materials, tubular constructs with trileaflet-shaped internal surface were obtained. By controlling the formation of the encapsulating tissue in the two-step in-body tissue incubation process, we were able to develop completely autologous trileaflet valve-shaped constructs.
Journal of Biomedical Materials Research Part B Applied Biomaterials 08/2009; 91(2):813-8. · 2.15 Impact Factor
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ABSTRACT: Port-site herniation is a rare but potentially dangerous complication after laparoscopic surgery. Closure of port sites, especially those measuring 10 mm or more, has been recommended to avoid such an event.
We herein report the only case of a port site hernia among a series 52 consecutive cases of laparoscopy-assisted distal gastrectomy (LADG) carried out by our unit between July 2002 and March 2007. In this case the small bowel herniated and incarcerated through the port site on day 4 after LADG despite closure of the fascia. Initial manifestations experienced by the patient, possibly due to obstruction, and including mild abdominal pain and nausea, occurred on the third day postoperatively. The definitive diagnosis was made on day 4 based on symptoms related to leakage from the duodenal stump, which was considered to have developed after severe obstruction of the bowel. Re-operation for reduction of the incarcerated bowel and tube duodenostomy with peritoneal drainage were required to manage this complication.
We present this case report and review of literature to discuss further regarding methods of fascial closure after laparoscopic surgery.
Journal of Medical Case Reports 02/2008; 2:48.
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Tsuyoshi Itoh,
Nobuaki Fuji,
Hiroki Taniguchi,
Satoru Yasukawa,
Hiroaki Yasuda,
Naoki Wakabayashi, Taiji Watanabe,
Toshiyuki Kosuga,
Kingo Kashimoto,
Akio Yanagisawa,
Kazuyo Naito
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ABSTRACT: We report a case of double cancer of the cystic duct and gallbladder associated with low junction of the cystic duct. A 73-year-old woman was admitted to the hospital complaining of upper abdominal pain. Endoscopic retrograde cholangiography showed a stenotic lesion in the lower common bile duct and no visualization of the cystic duct or gallbladder. Enhanced computed tomography revealed a heterogeneously enhanced tumorous lesion around the lower bile duct in the pancreatic head. A diagnosis of cancer arising from the cystic duct that entered the lower part of the common hepatic duct was made by intraductal ultrasonography, which showed an intraluminal protruding lesion in the cystic duct. Isolated gallbladder cancer was also diagnosed, by abdominal computed tomography. She underwent pancreaticoduodenectomy with dissection of regional lymph nodes. Histological examination revealed moderately differentiated adenocarcinoma of the cystic duct and well-differentiated adenocarcinoma of the gallbladder. Double cancer of the cystic duct and gallbladder is extremely rare, and this case also suggests a relationship between a low junction of the cystic duct and neoplasm in the biliary tract.
Journal of Hepato-Biliary-Pancreatic Surgery 02/2008; 15(3):338-43. · 1.60 Impact Factor
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ABSTRACT: We are developing functional autologous tubular tissues, called biotubes, as ideal small-caliber vascular grafts that have growth potential without immunological rejection. In this study, to improve surgical handling, a novel biotube reinforced at the anastomosis regions was designed. Silicone rods, 2 mm in diameter and used as a mold, were covered with two pieces of short polyurethane sponge tubing as anastomotic reinforcement cuffs at both ends. After the assembly was placed into dorsal subcutaneous pouches in rabbits for 1 month, seamless biotubes incorporating the cuffs were obtained. The interstices and surfaces of the cuffs were impregnated and covered with connective tissues similar to those of the biotubes, mainly consisting of collagen and fibroblasts. Since the tubular shape of both ends was rigidly maintained, end-to-end anastomosis by conventional microsurgery techniques between biotubes and native carotid arteries was very easy. In preliminary autoimplantation studies, angiographic observation of up to 2 months duration showed no formation of aneurysms or rupturing.
Journal of Artificial Organs 02/2007; 10(1):10-5. · 1.59 Impact Factor
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ABSTRACT: We report a case of ductal aneurysm after transcatheter coil embolization in an infant. The aneurysm was asymptomatic and was not detected until it ruptured during surgical intervention. We suspect that the aneurysm was induced by methicillin-resistant Staphylococcus aureus infection, as the resected aneurysmal wall was severely infiltrated by inflammatory cells and the patient had recurrent methicillin-resistant Staphylococcus aureus infection. We recommend remaining on guard against formation of a ductal aneurysm after coil embolization, especially in patients with associated recurrent bacteremia.
The Annals of thoracic surgery 02/2006; 81(1):339-41. · 3.74 Impact Factor
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ABSTRACT: A novel sutureless vascular connecting system, an assembly with a delivery rod, an introducing sheath, and a connecting device, was developed for easy implantation of small-caliber vascular grafts less than 2 mm in internal diameter. A microporous stainless tube (length 2 mm, external diameter 1.6 mm, wall thickness 65 microm, pore diameter 400 microm, pore-to-pore distance 500 microm) was designed to serve as a connecting device. The feasibility of the system was tested using two types of preliminary animal experiments. One animal model consisted of graft implantation into the rat abdominal aorta (1.5 mm in diameter). The connecting device was inserted into the proximal and distal ends of the aorta through the introducing sheath by pushing the delivery rod with the connecting device placed over it. Subsequently, the aortic segments were inserted into both ends of model grafts made of segmented polyurethane (1.8 mm in internal diameter) and were fixed with banding silk threads from the exterior. The procedure was completed within 20 min without requiring specialized microsurgery techniques. Blood leakage and obstruction did not occur. The second model consisted of an end-to-end anastomosis between rabbit common carotid arteries (2 mm in diameter), which was performed within several minutes of blood flow interruption. Scanning electron microscopy demonstrated that the luminal surface of the device was fully covered with endothelial cells (ECs) after 1 week as a result of transluminal ingrowth of native ECs through the micropores in the device. This endothelialization may prevent early thrombus-induced occlusion. This simple and "easy-to-learn" technique will promote the development of small-caliber arterial grafts, and furthermore, it may have potential for clinical application.
Journal of Artificial Organs 02/2005; 8(2):119-24. · 1.59 Impact Factor
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ABSTRACT: A new partial translocation technique to repair left ventricular rupture after mitral valve replacement and reimplant a mitral prosthesis is described. We repaired a tear from the interior by using mattress stitches buttressed with strips of Dacron felt, constructed a new annulus with a crescent-shaped piece of bovine pericardium on the left atrial wall above the repaired mitral annulus, and implanted a new prosthesis by using the newly constructed mitral annulus. We consider avoidance of mechanical stress by the prosthesis on the repaired site crucial to a successful outcome, and this new method is useful.
The Annals of thoracic surgery 11/2004; 78(5):1851-3. · 3.74 Impact Factor
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Yasuyuki Shimada,
Hitoshi Yaku,
Keisuke Shuntoh,
Katsuhiko Oka,
Takahisa Okano,
Tsutomu Matsushita,
Atsushi Fukumoto,
Kyoko Hayashida,
Yoshiaki Yamada, Taiji Watanabe,
Nobuo Kitamura
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ABSTRACT: Angiotensin-converting enzyme (ACE) inhibitors have cardioprotective effects in animals, but whether that occurs in humans is still controversial. The effect of myocardial ACE activity on coronary vascular resistance during coronary artery bypass surgery and on serum brain natriuretic peptide (BNP) concentration after surgery was studied in myocardial tissue sampled from the right atrium of patients during cardiac surgery (n=20). Tissue enzyme activity (nmol/min per mg protein) was measured using a photometric technique, and the flow rate and pressure upon antegrade infusion of a crystalloid cardioplegic solution was measured for calculating the coronary vascular resistance (mmHg. ml(-1). min(-1)). Serum BNP concentration (pg/ml) was measured on days 0 and 5 after the surgery. Linear regression between tissue ACE activity and coronary vascular resistance (y = 0.46x + 0.56, r=0.85) as well as serum BNP concentration on days 0 (y = 129x + 30, r=0.59) and 5 (y = 347x + 180, r=0.73) after the surgery was significant (x: ACE activity; y: coronary vascular resistance/serum BNP concentration). The results indicate that inhibition of myocardial ACE activity might improve coronary circulation during surgery and hence, cardiac function after surgery.
Circulation Journal 06/2003; 67(5):379-83. · 3.77 Impact Factor
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Kyoko Hayashida,
Keiichi Kanda,
Tomonori Oie,
Yosihiro Okamoto,
Osamu Sakai, Taiji Watanabe,
Hatsue Ishibashi-Ueda,
Masaaki Onoyama,
Tsutomu Tajikawa,
Kenkichi Ohba,
Hitoshi Yaku,
Yasuhide Nakayama
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ABSTRACT: "In body tissue architecture" technology is a practical concept of regenerative medicine that uses the living recipient body's reaction to a foreign object as a reactor for autologous tissue organization. A novel autologous valved conduit was produced by creating a specially designed conduit-mold composite and elastomeric scaffold for this unique in vivo tissue engineering.
Convex and concave plastic molds assembled with a small aperture of 500-800 microm were inserted into a microporous elastomeric conduit scaffold. The assembly was placed in a subcutaneous pocket of Japanese white rabbits for 1 month. The molds were pulled out from the edge of the harvested implant to obtain the valved conduit.
Homogenous and well-balanced trileaflet of membranous tissue was developed in the optimized aperture of molds. The valve leaflet closed and opened rapidly in synchronization with the backward and forward flow of the pulsatile flow circuit in vitro.
A tissue-engineered conduit incorporated with a functional autologous trileaflet valve was developed in an in vivo reactor by optimizing the microstructures of conduit scaffolds and newly designing the composite molds. The method holds promise for a safe, biocompatible, and economical heart valve prosthesis.
The Journal of cardiovascular nursing 23(1):61-4. · 1.43 Impact Factor
