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Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 19 recordsLinked to original sources
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

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↗
PubMed1996

New biodegradable oligoesters for pharmaceutical application.

Tartaric acid, malic acid, and glyceric acid were copolycondensed with glycolic acid at various molar ratios in feed to quickly synthesize biodegradable oligoesters. They were likely to have a moderately cross-linked structure with relatively low molecular weights and hydrophilic groups on the chains. In addition to macroscopic gels which were insoluble in any solvents, we could obtain the oligoesters which were insoluble in water but soluble in N,N-dimethylformamide. The degradation rate of the oligoesters was higher than that of lactic acid (LA) oligomers having molecular weights of a few thousands. On the contrary, their glass transition and flow temperatures were much higher than those of LA oligomers, indicating that their handling during the preparation of drug delivery dosage forms was much improved. The formulation of microspheres containing drugs from the oligoesters revealed that they were useful as biodegradable matrices having high degradation rates.

Antineoplastic Agents↗
PubMed1995

In vitro evaluation of cytotoxicity of diepoxy compounds used for biomaterial modification.

The toxicity of various diepoxy compounds used for biomaterials crosslinking was investigated with a cell culture method and compared with an in vivo method. The neutral red uptake by cells was used to count the number of cells still alive after contact with the diepoxy compounds, because this method was more sensitive in cell counting than the other four methods studied in this work. The amount of neutral red taken up by cells depended strongly on the activity of cells in comparison with other methods; only small amounts of neutral red were taken up when cells were in a low activity state even if they were still alive. The in vitro toxicity of diepoxy compounds evaluated by the neutral red method revealed a good correlation with that found by the in vivo Draize test. The in vitro cytotoxicity to a cell line of L929 was closely related to that of primary culture cells of the normal rabbit cornea epidermal cell. The toxicity of diepoxy compounds was lower as their chain was longer, probably because of the lower chemical reactivity. All the diepoxy compounds investigated in this study exhibited lower cytotoxicity than formaldehyde, glutaraldehyde, and a water-soluble carbodiimide.

Animals↗
PubMed1995

Fate of water-soluble polymers administered via different routes.

The biological fate of synthetic water-soluble polymers administered to mice by injection at different sites is described. After intraperitoneal (ip), subcutaneous (sc), and intramuscular (im) injections of 125I-labeled poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) with various molecular weights, the time-course of polymer concentration in the blood was measured and analyzed pharmacokinetically. The location of PVA in the body was similar to that of PEG; that is, the elimination from the injection sites and the translocation from the injection sites into the blood circulation were similar for both polymers. The elimination rate of both polymers from the injection sites increased in the order ip > sc > im. After sc and im injections of polymers, the elimination rate decreased with an increase in the molecular weight, whereas the elimination rate of polymers injected showed no molecular weight dependence over the range studied, regardless of the type of polymers used. The time-course of polymer concentration in the blood depended largely on the injection route of the polymers, and the polymer elimination from the blood circulation was enhanced with the decreasing molecular weight of polymers injected. It was concluded that the molecular weight and the injection site are the important factors that affect the concentration profile of polymers in the blood circulation.

Alcohols↗
PubMed1995

Further applications of "bilayer artificial skin".

A "bilayer artificial skin", composed of an inner layer of collagen sponge and an outer silicone layer, was developed by modifying the material reported by Yannas and Burke. Since our early results from experimental and clinical use of the original version of the "bilayer artificial skin" were reported, several improvements have been made in stages to eliminate some drawbacks related to disinfection and preservation and to reduce the primary cost of manufacture. The latest version of the material was successfully used in 27 sites on 23 patients. In this paper, the improvements in the material and the clinical results are described.

Adolescent↗
PubMed1995

Simple method for platelet counting.

A method is proposed for counting the number of adhered platelets based on the determination of lactate dehydrogenase activity in bulk after lysis of adhered platelets. This method was compared with the widely used radioisotope labelling technique. It was concluded that the present lactate dehydrogenase method is effective in counting the adhered platelets, as no significant difference was found between the readings of two methods when commercial polymers and glass were used as samples.

Biocompatible Materials↗
PubMed1995

Degradation of high molecular weight poly(L-lactide) in alkaline medium.

To study the effect of molecular weight and morphology on hydrolytic degradation, four poly(L-lactide)s (PLLAs) with average molecular weight of 3.0 x 10(5), 4.5 x 10(5), 6.5 x 10(5) and 3 x 10(6) were used. PLLA films with different morphologies were obtained by solution casting. Degradation of the films was performed at 37 degrees C in 0.01 N NaOH solution and this alkaline hydrolysis seemed to simulate well the real case while offering significant acceleration of the degradation process. Diverse microscopy techniques (light, polarizing and scanning electron) were used to study the surface change of morphology and erosion of the PLLA films. Swelling was visualized by scanning electron microscopy, particularly on the spherulites, which were eroded from the centre by hydrolysis. In the case of highly amorphous film, crystallization took place as degradation proceeded. The reduction in transparency of PLLA films, measured by a spectrophotometer at 570 nm, was ascribed to the increased density of spherulites. Differential scanning calorimetry revealed that the crystallinity of PLLA increased with degradation time, in accordance with accelerated spherulite formation.

Biocompatible Materials↗
PubMed1995

Potentiality of gelatin microsphere as immunological adjuvant.

This paper describes a new attempt to enhance the production of antibody by delivery of an antigen to phagocytic antigen-presenting cells (e.g. macrophages) using gelatin microspheres. A model protein antigen, human gamma globulin (HGG), was incorporated into microspheres composed of gelatin which have an opsonic ability for macrophage phagocytosis. Subcutaneous injection of the microspheres induced the production of HGG-specific IgG antibody in the mouse serum to a great extent compared with that of HGG in soluble form or in Freund's incomplete adjuvant (FIA) form. There was an optimal concentration of cross-linking agent (glutaraldehyde) for the highest production of antibody. When gelatin microspheres were cross-linked at lower concentrations of glutaraldehyde, they were more extensively swollen in an aqueous solution, leading to an increase in the size of hydrated microspheres because of their lower cross-linking densities. The increased size of microspheres caused a decrease in their macrophage phagocytosis, whereas the release rate of HGG from the microspheres increased as the concentration of cross-linking agent became low. The balance of the two factors, the microsphere susceptibility to macrophage phagocytosis and the rate of HGG release, seemed to affect the efficacy of gelatin microspheres to enhance the antibody production. In addition, incorporation of HGG into gelatin microspheres enhanced the delayed-type hypersensitivity reaction. Moreover, the microspheres developed a strong secondary response in comparison with FIA. The gelatin microspheres induced a minimal inflammatory response around the injection site in contrast to FIA. These findings demonstrate that the gelatin microsphere is promising as an adjuvant to enhance both humoral and cellular immune responses to antigen.

Adjuvants, Immunologic↗