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Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 127 records · Page 7Linked to original sources
PubMed1997

Reconstruction of mandibular continuity defects in dogs using poly (L-lactide) mesh and autogenic particulate cancellous bone and marrow: preliminary report.

PURPOSE: This study evaluated the reconstruction of continuity defects in the canine mandible using a poly [L-lactide] (PLLA) mesh tray and particulate cancellous bone and marrow (PCBM). MATERIALS AND METHODS: Eight adult dogs were divided into two groups of four dogs each. In group A, each dog had a tray fixed with stainless steel wires on each side of the mandibular stumps with the concave surface of the tray attached to the inferior border of the mandible (U-fixation). In group B, the concave surface was attached to the superior border (inverted U-fixation). Each tray was filled with PCBM from the ilium. After the operation, the dogs were radiographed, and specimens were examined histologically at 3-, 6-, and 12-month intervals. RESULTS: All of group A showed good clinical healing and the continuity of the mandibular bone was regained within 3 months postoperatively. However, fibrous tissue had invaded through the area above the tray, resulting in a poorly shaped alveolar ridges. In group B, the dogs showed good bony regeneration with well-shaped alveolar ridges. However, two animals in this group had partial exposure of the PLLA mesh tray into the oral cavity. CONCLUSION: It is suggested that a combination of the PLLA mesh and PCBM grafts might be a useful technique for functional reconstruction of the jaw bone, specifically using method A (U-fixation) as a technique to reconstruct continuity defects of the mandible, and method B (inverted, U-fixation) as a promising method for alveolar reconstruction to make wearing dentures possible.

Animals↗
PubMed1997

Immobilization of human thrombomodulin onto PTFE.

Human thrombomodulin (hTM) is an endothelial cell-surface glycoprotein and has effective anticoagulant properties. This protein was immobilized onto polytetrafluorethylene (PTFE) surfaces to create biomaterials with enhanced haemocompatibility. The PTFE surface was functionalized by CO2 plasma activation and subsequent vapour-phase graft polymerization of acrylic acid. Surface characterization after plasma treatment, grafting and hTM immobilization was achieved by attenuated total reflection-Fourier transform-infrared spectroscopy, X-ray photoelectron spectroscopy, zeta potential and wetting measurements. The activity of immobilized hTM was estimated using the protein C activation test.

Journal Article↗
PubMed1997

Biodegradable polymeric device for sustained intravitreal release of ganciclovir in rabbits.

PURPOSE: A scleral plug made of biodegradable polymer implanted at the pars plana was evaluated to determine its ability to control the intravitreal release of ganciclovir. METHODS: Scleral plugs containing 25% ganciclovir were prepared with poly(lactic-glycolic acid) (molecular weight, 121 kDa). The release of ganciclovir was evaluated in vitro by spectrophotometry. In vivo intravitreal ganciclovir concentrations were measured by high performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy, electroretinography, and light and electron microscopy. RESULTS: The in vitro study showed that the plug released ganciclovir throughout a 10-week period. The in vivo study demonstrated that the plugs maintained the drug concentration in the vitreous in a therapeutic range adequate to treat cytomegalovirus (CMV) retinitis for 12 weeks. No significant retinal toxicity was observed. CONCLUSIONS: This study demonstrated that this drug delivery system can potentially be useful to treat CMV retinitis.

Animals↗
PubMed1997

Biodegradable scleral implant for intravitreal controlled release of fluconazole.

PURPOSE: To evaluate the feasibility of using a biodegradable polymeric scleral implant containing fluconazole (FLCZ), a bis-triazole antifungal agent, as a potential intravitreal-controlled drug delivery system. METHODS: The scleral implants, loaded with 10, 20, 30, and 50% FLCZ, were prepared with biodegradable polymers of poly (DL-lactide-co-glycolide). Those with all loading doses were used for the in vitro release studies; those with 30% FLCZ were used for the intravitreal release studies in pigmented rabbits. The in vitro and in vivo release rates of FLCZ from the implants were measured periodically with spectrophotometry and high performance liquid chromatography, respectively. The effects of the implants on ocular tissues were evaluated ophthalmoscopically, histologically, and electrophysiologically. RESULTS: The scleral implants loaded with 10, 20, and 30% doses gradually released FLCZ over 4 weeks in vitro; those with 50% FLCZ released most of the drug in one week. FLCZ concentration in the rabbit vitreous remained within the 99% inhibitory concentration for Candida albicans for 3 weeks after implantation. The scleral implant gradually biodegraded, and it disappeared by 4 months after implantation. The electrophysiologic and histopathologic findings demonstrated no substantial toxic reactions in the ocular tissues. CONCLUSION: The current study suggests that a biodegradable, polymeric scleral implant containing FLCZ may be a promising intravitreal drug delivery system to treat fungal endophthalmitis.

Animals↗
PubMed1997

Selective delivery of 5-fluorouracil (5-FU) to i.p. tissues using 5-FU microspheres in rats.

A new formulation has been developed for the delivery of 5-fluorouracil (5-FU) in treating peritoneal carcinomatosis. The new formulation (5-FU-MS) involves the incorporation of 5-FU into microspheres composed of a poly(glycolide-co-lactide) matrix. The incorporated 5-FU is released slowly over a 3 week period. We investigated the drug distribution and pharmacokinetics of 5-FU in rats receiving an i.p. injection of 5-FU-MS or aqueous 5-FU solution. The concentration of 5-FU was higher in the i.p. tissues (omentum and mesentery) and lower in the extraperitoneal tissues (blood plasma, lung and heart) in rats given 5-FU-MS than in rats given the aqueous 5-FU solution. Pharmacokinetic analysis showed that the area under the curve (AUC) was significantly greater in the omentum and the mesentery than in other tissues of rats given 5-FU-MS. There was no significant difference in the AUC in the tissues of rats given the aqueous 5-FU solution.

Animals↗
PubMed1997

Photodynamic effect of polyethylene glycol-modified fullerene on tumor.

Fullerence (C60) efficiently generates singlet oxygen when irradiated with light, and thus should have a photodynamic effect on tumors, if it is accumulated in the tumor tissue. To explore tumor targeting of C60, we chemically modified the water-insoluble C60 with polyethylene glycol (PEG), not only to make it soluble in water, but also to enlarge its molecular size. When injected intravenously into mice carrying a tumor mass in the back subcutis, the C60-PEG conjugate exhibited higher accumulation and more prolonged retention in the tumor tissue than in normal tissue. The conjugate was excreted without being accumulated in any specific organ. Following intravenous injection of C60-PEG conjugate or Photofrin to tumor-bearing mice, coupled with exposure of the tumor site to visible light, the volume increase of the tumor mass was suppressed and the C60 conjugate exhibited a stronger suppressive effect than Photofrin. Histological examination revealed that conjugate injection plus light irradiation strongly induced tumor necrosis without any damage to the overlying normal skin. The antitumor effect of the conjugate increased with increasing irradiation power and C60 dose, and cures were achieved by treatment with a dose of 424 micrograms/kg at an irradiation power of 107 J/cm2. These findings indicate that PEG-modified C60 is a candidate agent for photodynamic tumor therapy.

Animals↗
PubMed1997

Encapsulation of mammalian cells into synthetic polymer membranes using least toxic solvents.

Immunoisolation, that is, enclosure of cells within a semipermeable membrane to protect them from immunological rejection, may enable the transplantation of cells without use of immunosuppressive drugs. Therefore, in addition to naturally-occurring ionic polymers, several synthetic nonionic polymers which can form dense and strong membranes in water have been studied as materials for immunoisolation. However, such nonionic polymers are required to be soluble in organic solvents which are mostly cytotoxic. In this report we describe enclosure of insulin-releasing cells into water-insoluble poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) membranes using X-ray contrast medium as a solvent without use of any special apparatus. The contrast medium employed in our study is iopamidol aqueous solution. Insulin release was observed for 1 months when insulin-releasing cells were encapsulated into these membranes. The permeability of five solutes through the membranes prepared from the iopamidol aqueous solution was also studied to determine their potential immunoisolative efficacy.

Animals↗
PubMed1997

Potential efficacy of basic fibroblast growth factor incorporated in biodegradable hydrogels for skull bone regeneration.

Biodegradable gelatin hydrogels incorporating basic fibroblast growth factor (bFGF) were evaluated for their efficacy in bone regeneration using a rabbit model. Hydrogels with water contents of 85% and 98% were prepared using chemical crosslinking of gelatin with an isoelectric point of 4.9 in aqueous solution and, after freeze drying, were impregnated with an aqueous solution of bFGF to obtain bFGF-incorporated gelatin hydrogels. When they were implanted into bone defects measuring 6 mm in diameter in rabbit skulls (six animals/group), complete closure of the defect was observed at 12 weeks after implantation, regardless of the water content of the hydrogels. In contrast, bFGF did not enhance bone regeneration when applied to the skull defect in solution with phosphate-buffered saline (PBS). Also, gelatin hydrogels lacking bFGF were not effective in inducing bone formation, with fibrous tissue growing into the defect instead, similar to the skull defect seen in control rabbits treated with PBS. This indicates that the presence of hydrogels did not interfere with bone regeneration at the skull defect, probably because of their disappearance during biodegradation. It is concluded that the gelatin hydrogel is a promising matrix for effective induction of biological activity of bFGF for bone regeneration in skull and sinus defects.

Animals↗
PubMed1997

Development of a dural substitute from synthetic bioabsorbable polymers.

A new bioabsorbable composite sheet was developed to provide a substitute for the dura mater and was evaluated histologically and biomechanically using rats and rabbits. This composite, composed of two L-lactic acid-epsilon-caprolactone (50% L-lactic acid, 50% epsilon-caprolactone) copolymer films and a poly(glycolic acid) nonwoven fabric, displayed good mechanical properties and was completely absorbed 24 weeks after implantation in the back of rats. Histological evaluation of the composite sheet was undertaken by implanting it in 31 rabbits with dural defects and examining the sites of implantation 2 weeks to 26 months later. No infection, cerebrospinal fluid leakage, evidence of convulsive disorders, significant adhesion to underlying cortex, or calcification was noticed in any cases. In addition, the regenerated duralike tissue had a high pressure-resistant strength 2 weeks after implantation. The authors conclude that this new bioabsorbable composite sheet can be successfully used as a dural substitute.

Absorption↗
PubMed1997

Characterization and transplantation of agarose microencapsulated canine islets of Langerhans.

The bioartificial pancreas was designed to incorporate islet tissues and a selectively permiable membrane that isolates islets from the immune system of the recipient. The efficacy of agarose, a nontoxic polysaccharide, has been evaluated as a material of microcapsules to prevent allo- and xenograft rejection in rodents. The aim of this study is to demonstrate the possibility of the agarose microcapsule containing allo-islets as a bioartificial pancreas in canine model. In vitro viability of islets was determined by glucose challenge during perifusion experiments (n = 4). Insulin secretion from both encapsulated (enc.) and non-encapsulated (non-enc.) canine islets rose from initial basal levels of 0.09 (encap.), 0.07 (non-encap.) to the peak of 0.2 (encap.), 0.1 (non-encap.) in microU/islet/min after 5 minutes, then decreased to the basal level when the glucose challenge was discontinued. Auto-transplantation was performed in two dogs to evaluated in vivo viability and biocompatibility of encapsulated islets implanted into the splenic sinus by venouse reflux. Two weeks after auto-transplantation, the plasma insulin levels in the splenic vein and artery of two dogs were assayed. In the first dog, serum insulin level was 1 microU/ml both in the vein and the artery and increased, after glucagon (1.0 mg) injection, to levels of 9 microU/ml in the vein, but still kept 1 microU/ml in artery, as well as in the second one. Histological and electron-microscopical examination of the spleen revealed that encapsulated islets remained morphologically intact and the surface of agarose capsules showed no significant adherence of fibroblasts and inflammatory cells. Functional efficacy of the microencapsulated islets was determined using five totally-pancreatectomized diabetic dogs as recipients without immunosuppression. Defined quantity of microencapsulated islets from outbred mongrel donors were grafted through the catheter into omental tissue of the pancreatectomized recipients. All dogs had various degrees of reduced insulin requirements. In three of five recipients, the average fasting glucose values were controlled under 120 mg/dl for 28, 42, 49 days without exogenous insulin, which received totally 4.3 x 10(3), 7.3 x 10(3) and 1.0 x 10(4) (IE/kg) of microencapsulated islets, respectively. In conclusion, the present study indicates that the agarose-based microencapsulated islets can function in large diabetic animals, resulting in the independence of exogenous insulin therapy for prolonged periods without the need for immunosuppression.

Animals↗
PubMed1996

In vitro platelet adhesion to nonionic and ionic hydrogels with different water contents.

To investigate in vitro platelet adhesion to hydrogels, using electron-beam irradiation, polymer reaction, and radical polymerization, hydrogels were synthesized to have a wide range of water content. The nonionic synthesized hydrogels include polyacrylamide (PAAm), poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), poly(N-vinyl pyrrolidone), and poly(methoxy-PEG methacrylate) while the ionic hydrogels were crosslinked poly(AAm-acrylic acid) and poly(AAm-dimethylaminoethyl methacrylate) copolymers. Adhesion of washed rabbit platelets to these hydrogels were studied in phosphate-buffered saline for 30 min. In the case of PVA and PAAm hydrogels, platelet adhesion also was conducted in the presence of proteins. The protein sorption into PVA hydrogel was studied by fluorescent spectroscopy. It was found that all the nonionic hydrogels exhibited a lower level of platelet adhesion than did conventional hydrophobic polymers, such as medical-grade poly(vinyl chloride), polyurethane, and silicone, and they exhibited the minimum platelet adhesion at a water content of around 90%. PAAm and PEG hydrogels had the weakest interaction with platelets when the water content was lower than 90%. PVA hydrogel showed the highest platelet adhesion in the low-water-content region, but the platelet adhesion was greatly reduced in the presence of proteins. Significant protein sorption was noted when the water content of PVA hydrogel was as high as 80%. Introduction of a positive charge into the PAAm hydrogel promoted platelet adhesion whereas the negative charge introduced into the hydrogel slightly reduced the number of adhered platelets.

Adsorption↗
PubMed1996

Enhancement of bone formation by drawn poly(L-lactide).

Poly(L-lactide) (PLLA) was molded into films and rods, and drawn in the longitudinal direction to endow them with piezoelectricity. The piezoelectric constants of PLLA films increased with the draw ratio and, after passing a maximum at a draw ratio around 5, decreased. PLLA samples with a draw ratio 5 underwent fibrilization. The PLLA rods were intramedullarily implanted in the cut tibiae of cats for internal fixation up to 8 weeks. Fracture healing was clearly promoted with increased callus formation as the draw ratio of the PLLA rod increased, whereas the undrawn PLLA as well as a polyethylene control rod had no effect on callus formation, or rather, retarded it. This finding strongly suggests that the promotion of fracture healing by fixation with drawn PLLA can be ascribed to the piezoelectric current generated by the strains accompanying leg movement.

Animals↗
PubMed1996

A new biological glue from gelatin and poly (L-glutamic acid).

This study describes the potentiality of hydrogels composed of gelatin and poly(L-glutamic acid) (PLGA) as a biological glue for soft tissues and compares its effectiveness with that of a conventional fibrin glue. Water-soluble carbodiimides (WSC) were used to crosslink the aqueous mixture of gelatin and PLGA. The mixed aqueous solution of gelatin and PLGA set to a hydrogel by use of WSC as rapidly as BOLHEAL fibrin glue. An addition of PLGA to gelatin aqueous solution reduced not only its gelation time but also the WSC concentration necessary for hydrogel formation. The cured hydrogel exhibited firm adhesion to the mouse skin and other soft tissues with a higher bonding strength than BOLHEAL fibrin glue. Cohesive failure in the hydrogel was observed when the gel-tissue bond was broken, in contrast to BOLHEAL fibrin glue. The bonding strength of the gelatin-PLGA hydrogel became higher with the increasing PLGA concentration. The inflammatory reaction around the gelatin-PLGA hydrogel subcutaneously implanted in mice was mild, and the hydrogel was gradually absorbed with time in vivo. A toxicity test demonstrated that the concentration of WSC necessary as a biological glue was low enough not to induce its toxicity.

Adhesives↗
PubMed1996

Production of interleukin 1 from macrophages incubated with poly (DL-lactic acid) granules containing ovalbumin.

The production profile of interleukin 1 (IL-1) from mouse peritoneal macrophages (M phi) was determined following their incubation with poly(DL-lactic acid) (PDLLA) granules containing ovalbumin (OVA). Upon incubation, M phi produced IL-1 at a significantly high rate compared with those incubated with OVA in the free form or OVA-free granules. A simple mixture of empty granules and free OVA exhibited the same level of IL-1 production as induced by free OVA alone. IL-1 production by the granules with a fixed OVA loading increased with an increase in their amount added to M phi. When incubated with a fixed amount of granules containing OVA of different loadings, M phi produced more IL-1 with an increase in the total OVA amount, but the IL-1 production decreased at OVA loadings higher than 10%. The presence of free OVA enhanced IL-1 production with the increased addition of empty granules, but the level induced by OVA loaded in granules was higher than that by mixtures of free OVA and empty granules, when compared at a similar OVA dose, irrespective of the absolute amount of PDLLA added. These findings indicate that the sustained release of OVA from the granules is critical to enhance the OVA-induced IL-1 production, in contrast to the OVA release accompanying a large initial burst, which reduced IL-1 production. It was concluded that the direct contact of PDLLA granules with M phi and the subsequent sustained release of OVA around M phi effectively activated M phi, resulting in enhanced IL-1 production.

Animals↗
PubMed1996

Effect of basic fibroblast growth factor on cartilage regeneration in chondrocyte-seeded collagen sponge scaffold.

A chondrocyte-collagen composite was prepared in an attempt to regenerate cartilage by its subcutaneous implantation in nude mouse. When the composite was impregnated with basic fibroblast growth factor (bFGF) prior to implantation, regeneration of the cartilage tissue was remarkably accelerated. Histological staining of the implanted composites with Safranin O-fast green revealed that the cells incorporated in the composites exhibited their phenotype and formed a new matured cartilage. A thin layer of fibrous capsule was observed surrounding the implanted composite and the inflammatory response of the host to the implant was mild. Specific proteoglycans were accumulated in the composite even 1 week after implantation. At 2 weeks after implantation, the chondrocytes regenerated the cartilage tissue, although still immature, but at 4 weeks almost all of the chondrocytes transferred to the mature stage. Conversely, such mature cartilage tissue was not noticed up to 4 weeks after implantation if the collagen scaffold was not impregnated with bFGF. Moreover, the mature area was limited to only a small fraction of the implanted composite, unless bFGF was incorporated in it.

Animals↗
PubMed1996

Significance of interstitial bone ingrowth under load-bearing conditions: a comparison between solid and porous implant materials.

Interstitial bone ingrowth is extremely important for optimum fixation of implanted materials under load-bearing conditions. In this study, three types of biomaterial test piece were manufactured in solid and open-pore structures, and implanted into dog femoral condyles. Bone formation and remodelling were observed histologically and roentgenologically for 24 weeks thereafter. The study demonstrated that, 24 weeks after implantation, thick fibrous tissue surrounded by corticalized bone formed around both solid smooth-surfaced alumina and titanium implants. On the other hand, however, with an implant made of an artificial osteochondral composite material, thickening of ingrown trabeculae could be observed as early as 4 weeks. Bone ingrowth into the titanium fibre mesh was ambundant and increased with time after implantation. This interstitial bone ingrowth resulted in the complete integration of this implant and the viable host bone. Our findings suggest that interstitial bone ingrowth has great significance, even though new bone formation and remodelling follows Wolff's law after the completion of the bonding between the bone and implanted material under load-bearing conditions. The artificial osteochondral composite material could lead to complete integration of the implant and viable bone, suggesting that it is a promising material for joint replacements. Moreover, the tibial joint surface which bore against the polyvinyl alcohol hydrogel surface of this implant remained intact, which suggests that this composite is a very promising biomaterial for use in joint prostheses.

Animals↗
PubMed1996

Rapidly curable biological glue composed of gelatin and poly(L-glutamic acid).

The tissue adhesion property of a hydrogel cross-linked with water-soluble carbodiimide (WSC) was investigated and compared with that of the conventional fibrin glue. The biodegradable hydrogel was composed of gelatin and poly(L-glutamic acid) (PLGA). This study focused on the mouse skin bonding by the WSC-formed hydrogel prepared from a low-molecular-weight (Mw) gelatin whose aqueous solution did not spontaneously set to a gel at 25 degrees C, in contrast to the conventional gelatin with high Mw. At polymer concentrations lower than the incipient gelation concentration, the bonding strength of mouse skin by the WSC-cross-linked gelatin-PLGA hydrogel increased with an increase in the concentration of gelatin and PLGA, irrespective of Mw of gelatin. When compared at the highest gelatin concentration which did not cause gelation, the bonding strength of the hydrogel composed of lower Mw gelatin and PLGA was higher than that of higher Mw gelatin hydrogel with or without PLGA or the conventional fibrin glue. The mixed aqueous solution from the gelatin with Mw of 10,000 and PLGA was gelled by use of WSC as rapidly as the fibrin glue. It was concluded that the gelatin-PLGA hydrogel is a safe biological glue with the adhesion property superior to the fibrin glue.

Adhesives↗