Biomedical subjects

Yoshito Ikada

Publications and source records attributed to Yoshito Ikada.

28 records · Page 2Linked to original sources

PubMed2003

Creating bioabsorbable Schwann cell coated conduits through tissue engineering.

Enormous effort has been devoted to the generation of a synthetic guidance conduit for nerve repair instead of utilizing autograft. Several studies show neural guidance conduit is more effective when coated with Schwann cells. In this study, we synthesized bioabsorbable conduit consist of L-lactide and epsilon-caprolactone which was useful clinically and examined adhesion of Schwann cells to bioabsorbable conduits. In vivo studies were done in which these polymer conduits coated with Schwann cells were implanted across a 12 mm gap in the rat sciatic nerve. Silicone conduits were implanted across the same gap as control. At 12 weeks, axonal regeneration was observed in the midconduit region of these polymer conduits and was not in control. This study assesses the feasibility of a tissue engineering approach to constructing bioabsorbable conduits coated with Schwann cells.

Absorbable Implants↗

PubMed2002

Liver targeting of human interferon-beta with pullulan based on metal coordination.

Although interferon (IFN)-beta is widely used for the elimination of hepatitis C virus in patients with chronic liver disease, its clinical efficacy is unsatisfactory. Targeting IFN-beta to the liver might enhance its efficacy without increasing its side effects. The objective of the present study was to target IFN-beta to the liver to enhance its biological activity and reduce its side effects. A chelating residue, diethylenetriaminepentaacetic acid (DTPA), was introduced to pullulan, a water-soluble polysaccharide with a high affinity to the liver (DTPA-pullulan) and natural human IFN-beta was coordinately conjugated with the DTPA-pullulan by mixing in an aqueous solution containing zinc ions (Zn(2+)). Intravenous injection of the IFN-beta-DTPA-pullulan conjugate with Zn(2+) coordination into mice enhanced induction of an antiviral enzyme, 2',5'-oligoadenylate synthetase (2-5AS), specifically in the liver to a significantly greater extent than free natural IFN-beta. The enhanced 2-5AS level in the liver depended on the molar mixing ratio of IFN-beta, DTPA residue of the DTPA-pullulan, and Zn(2+). Moreover, the duration of the liver 2-5AS induction by the IFN-beta-DTPA-pullulan conjugate was longer than that by free natural IFN-beta. Thus, human IFN-beta-DTPA-pullulan conjugate appears to be applicable for clinical use, which is promising for treatment of patients with chronic hepatitis C.

Animals↗

PubMed2002

Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells for chronic inflammatory colitis.

We developed two kinds of delivery systems targeting mucosal immune regulating cells with poly (D,L-lactic acid) microspheres containing dexamethasone and dichloromethylene diphosphonate, and gelatine microspheres containing interleukin-10. To estimate the efficacy of these drug delivery systems, we studied the effects on experimental colitis induced by dextran sodium sulfate, 2,4,6-trinitrobenzene sulfonic acid, and interleukin-10-deficient mice. Intestinal administration of these microspheres significantly improved colitis with decreased histological score, myeloperoxidase activity, and nitric oxide production compared with mice treated with free agents. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in treated animals. Serum Dx, IL-10 levels, and systemic macrophages were unchanged after treatment. Our findings suggest that local macrophages in the intestine play a critical role in the initiation of chronic colitis in the animal model of inflammatory bowel disease (IBD). Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells may become a therapeutic approach to human IBD.

Animals↗

PubMed2002

Evaluation of the antiadhesion potential of UV cross-linked gelatin films in a rat abdominal model.

Among five kinds of rat adhesion models tested, the following model was selected. The epigastric vein 2.5 cm from the midline of the abdomen was cut by sharp scissors, and the lateral side of the cut epigastric vein was ligated using a 3-0 silk suture. This model could be easily prepared and gave a rate of adhesion formation of 90%, which was useful for screening antiadhesive materials. For the kinetic study of tissue adhesion in this model, an injured site was covered with a non-degradable poly(vinyl alcohol) (PVA) film. The incidence rate of adhesion was 18%, when the PVA film covered the injured site for 2 days. This suggests that an antiadhesive barrier should cover the injured site for at least 2 days. The antiadhesion efficacy of cross-linked gelatin films were evaluated using this adhesion model. The UV cross-linked gelatin film which was designed to exist for 2 days but to disappear at day 3 in the rat abdominal cavity showed the highest antiadhesion efficacy.

Abdominal Cavity↗

PubMed2002

Clinical application of a new bioabsorbable artificial dura mater.

OBJECT: In their pursuit of a better substitute for dura mater in neurosurgical procedures, the authors review their experience with GM972. METHODS: A newly developed synthetic dural substitute composed of bioabsorbable polymers (GM972) was placed in 53 patients during neurosurgical procedures. The handling properties of the material, surgical wound features. and findings of hematological, computerized tomography, and/or magnetic resonance imaging examinations were evaluated. The average follow-up period was 35.5 months. The handling properties and biocompatibility of this new dural substitute were highly satisfactory, and no significant complication was observed. In patients who underwent a second surgery performed more than 18 months after the initial operation, this new dural substitute was found to have been replaced by autologous collagenous tissue. Because of its bioabsorbability, chronic foreign body reactions to this synthetic dural substitute were negligible. CONCLUSIONS: In this report the authors support the effectiveness and safety of this bioabsorbable artificial dural substitute that provides a reduced risk of transmission of latent infection.

Absorbable Implants↗

PubMedDate not supplied

Tissue-engineered patch for the reconstruction of inferior vena cava during living-donor liver transplantation.

In living-donor liver transplantation, only a portion of the donor's liver is grafted into the recipient; therefore, if the hepatic vein and inferior vena cava (IVC) in the recipient fail to be transformed or dilated properly, it could cause inadequate blood flow from the liver graft to the IVC. We have developed an easy-to-use tissue engineered patch that can be used for the reconstruction of the hepatic vein and IVC. Five hybrid pigs (weighing 15-30 kg) served as the recipients of the patch. A bioabsorbable polymer sheet was used to produce the patch, with no cells seeded. The pigs were laparotomized, followed by the removal of a 3 x 2-cm portion of the infrahepatic IVC, which was then patched with the polymer sheet. Three months after the operation, the graft site was removed and subjected to gross and histologic examinations. All five pigs survived until they were killed 3 months after the operation. On gross examination, the polymer sheet grafted onto the IVC was completely absorbed, and the graft site was morphologically similar to the native IVC. In all five pigs, the patched IVC was free of stenosis or deformation. Immunohistochemical examination revealed that the patch site was lined with endothelial cells and that smooth muscle was present under the epithelium. Like the native IVC, the patch site tested positive for factor VIII. These findings suggest that this polymer sheet may be useful for the reconstruction of the IVC and hepatic vein during living-donor liver transplantation in humans.

Absorbable Implants↗

PubMedDate not supplied

Tissue engineering of an auricular cartilage model utilizing cultured chondrocyte-poly(L-lactide-epsilon-caprolactone) scaffolds.

To determine the potential development in vivo of tissue-engineered auricular cartilage, chondrocytes from articular cartilage of bovine forelimb joints were seeded on poly(L-lactic acid-epsilon-caprolactone) copolymer scaffolds molded into the shape of a human ear. Copolymer scaffolds alone in the same shape were studied for comparison. Chondrocyte-seeded copolymer constructs and scaffolds alone were each implanted in dorsal skin flaps of athymic mice for up to 40 weeks. Retrieved specimens were examined by histological and molecular techniques. After 10 weeks of implantation, cell-seeded constructs developed cartilage as assessed by toluidine blue and safranin-O red staining; a vascular, perichondrium-like capsule enveloped these constructs; and tissue formation resembled the auricular shape molded originally. Cartilage matrix formation increased, the capsule persisted, and initial auricular configuration was maintained through implantation for 40 weeks. The presence of cartilage production was correlated with RT-PCR analysis, which showed expression of bovine-specific type II collagen and aggrecan mRNA in cell-seeded specimens at 20 and 40 weeks. Copolymer scaffolds monitored only for 40 weeks failed to develop cartilage or a defined capsule and expressed no mRNA. Extensive vascularization led to scaffold erosion, decrease in original size, and loss of contour and shape. These results demonstrate that poly(L-lactic acid-epsilon-caprolactone) copolymer seeded with articular chondrocytes supports development and maintenance of cartilage in a human ear shape over periods to 40 weeks in this implantation model.

Animals↗

PubMedDate not supplied

Bioartificial liver with whole blood perfusion.

In our series of studies, we have made an effort to develop a bioartificial liver (BAL) system through which whole blood can be perfused as in hemodialysis therapy. In this study, BAL cartridges containing porcine hepatocytes were prepared and perfused in an extracapillary space with human whole blood in vitro. Lidocaine loading tests were performed to evaluate the detoxification ability of the BAL. The clearance value of lidocaine decreased during the initial 6 hours to about 50% of the initial value. After that, it was almost stable until 48 hours. After 48 hours perfusion, thin sections of the hollow fibers containing hepatocytes were prepared and stained with hematoxylin-eosin and immunohistochemically stained for membrane attack complex (MAC). The porcine hepatocytes formed aggregates in the hollow fibers, nuclei in the cells were observed clearly, and MAC was not seen on the porcine hepatocyte aggregation. A hollow fiber that can reject 90% of molecules with molecular weight of 50 kDa effectively protects porcine hepatocytes from humoral immunity. The in vivo assessment of the BAL cartridge was performed using a canine model for 24 hours. No significant hemolysis or thrombus that affected the BAL system and the canine were observed. These results suggest that our BAL system is a promising liver assist device through which patients' whole blood can be perfused.

Animals↗

PubMedDate not supplied

Transcatheter arterial embolization using poly-L-lactic acid microspheres.

PURPOSE: To assess the use of poly-L-lactic acid (PLLA) microspheres as an embolic material in transcatheter arterial embolization (TAE). MATERIALS AND METHODS: Between December 1993 and August 1995, eight patients [dural arteriovenous fistula (AVF) (n = 1), acute hemoptysis (n = 7)] underwent nine TAE procedures using PLLA microspheres. The patients were four men and four women, aged 38-82 years (mean, 62.4 years). All procedures were performed through a 3-F microcatheter inserted coaxially into a 5-F angiographic catheter via the right femoral artery. RESULTS: TAE using PLLA was technically successful in all patients. Flow stasis of the targeted arteries was obtained immediately after TAE. Clinical symptoms improved immediately after the procedure, and there was no recurrence during the follow-up period. Procedure-associated complications were not observed, except for slight fever up to 38 degrees C for three days that was managed conservatively. CONCLUSION: PLLA appeared to be a suitable embolic material for use in TAE when permanent occlusion is required. As PLLA particles can be prepared in any size, they are suitable for distal occlusion of arteries, thus avoiding proximal occlusion where the recruitment of collaterals is problematic.

Aged↗

PubMedDate not supplied

A historical review of artificial cornea research in Japan.

Little is known or understood about the history of artificial cornea (keratoprosthesis) in Japan, mainly because of the unavailability and linguistic inaccessibility of the relevant publications. Rather strangely also, the Japanese scholars themselves have manifested only slight interest in reviewing the topic, even in their own language. As a result, the research on artificial cornea in Japan showed in fact the same pattern of historical development as that seen in the Western world. After audacious beginnings in the 19th century, an interlude of about half a century followed, when the interest of ophthalmologists was deflected to penetrating keratoplasty as a means to fight corneal blindness. The introduction in medical use of man-made polymeric materials in the 1950s triggered a revival of research on artificial cornea in Japan, and the next two decades were rich in ideas, achievements, and a plethora of reports, all published in Japanese. In the 1980s, the developmental work on keratoprosthesis became incorporated into the field of biomaterials, and the creation of materials able to mimic the corneal tissue was established as a leading concept, resulting in original designs with some sophistication. At the same time. the English language started to be used extensively for dissemination of results. These trends have continued to date. Based on rigorous documentation, we traced the history of research on artificial cornea in Japan from its origin to our time.

Animals↗