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Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1995

Comparison of body distribution of poly(vinyl alcohol) with other water-soluble polymers after intravenous administration.

The body distribution of poly(vinyl alcohol) (PVA) with molecular weights (MW) from 14,800 to 434,000 Da was investigated after intravenous administration and compared with that of other water-soluble polymers such as poly(ethylene glycol) (PEG), gelatin, dextran, and pullulan. The half-life of PVA in the circulation was prolonged from 90 min (MW 14,800 Da) to 23 h (MW 434,000 Da), similar to that of PEG which had a half-life of 30 min (MW 6000) and 20 h (MW 170,000). However, the half-life of PVA was much longer than that of other polymers when compared at a similar molecular weight. PVA was located in most organs but with very small accumulation. An insignificant interaction of PVA with cell components, such as macrophages and blood cells, was observed. Similar to PEG, the excretion rate of PVA at the glomeruli was rapidly reduced around 30,000 Da, as the molecular weight increased. These results indicate that the half-life of intravenously injected PVA in the blood was mainly determined by the permeation characteristics of the kidney.

Animals↗
PubMed1995

In vivo chondrogenesis in collagen sponge sandwiched by perichondrium.

In order to increase the cartilage synthesis of the perichondrium, we combined auricular perichondrium with a collagen sponge as a template (perichondrium-sandwiched collagen sponge) and implanted the assembly as an autograft into the back of rabbits. Microscopic examination revealed that cartilaginous tissue was produced in the collagen sponge and chondrosynthesis was accelerated in the collagen sponge implants in comparison with that in materials containing perichondrium alone.

Animals↗
PubMed1995

Surface modification of silicone for percutaneous implantation.

In order to prevent epidermal down growth when a silicone percutaneous device was implanted, immobilization of collagen was performed onto the surface of a silicone device. The immobilization of collagen was achieved through covalent bonds between the amino groups in the collagen molecules and the carboxyl groups in poly (acrylic acid) chains grafted onto the silicone device surface. When the collagen-immobilized silicone device model was percutaneously implanted in rabbits, no sign of epidermal down growth was observed even 7 weeks after implantation, while the epidermis reached down to the deep part of the dermis as early as 3 weeks after implantation when collagen was not immobilized onto the device model surface. To have tighter fixation of the device models to the surrounding dermal tissue, the silicone device model was covered with a polyethylene sponge having an average interconnecting pore size of 150 microns. Collagen immobilization was also performed onto the sponge surface. Both the collagen-immobilized silicone device models as well as the non-treated models with polyethylene sponge were percutaneously implanted in rabbits and epidermal down growth as well as the occurrence of bacterial infection was examined. Without collagen immobilization onto the sponge surface of the device model, bacterial infection was noticed as early as 2 weeks after the implantation. The number of infected device models increased as the implantation time became longer and bacterial infection was observed in six out of seven device models at the 10th week post implantation. When the sponge surface was immobilized with collagen, bacterial infection was noticed in only one model at the 5th week after implantation. Six out of seven implanted device models with collagen immobilization were free of bacterial infection until the animals were sacrificed 30 weeks after implantation.

Animals↗
PubMed1995

Implantable biodegradable polymeric device in the treatment of experimental proliferative vitreoretinopathy.

We investigated the use of a scleral plug of biodegradable polymer implanted at the pars plana to create a controlled drug-delivery system in the vitreous. We evaluated the efficacy of a plug containing doxorubicin hydrochloride to treat experimental proliferative vitreoretinopathy (PVR) in pigmented rabbits. An implantable device on the sclera, which imitates a scleral plug, containing 1% doxorubicin, was prepared with poly(lactic acid) (molecular weight, 20,000). The release of doxorubicin in phosphate-buffered saline was evaluated by spectro-photometry. After pars plana vitrectomy and plug implantation, concentrations of doxorubicin in the vitreous humor of the rabbits were measured by high performance liquid chromatography. The release profiles were evaluated during 5 weeks in vitro and 4 weeks in vivo. Cultured homologous fibroblasts were injected into the vitreous space to induce experimental PVR after gas compression of the vitreous. The scleral plugs were implanted at the pars plana in treatment animals (n = 11). Control rabbits (n = 11) were followed up without implantation after PVR induction. All eyes of the control group developed tractional retinal detachment at day 28, while the incidence of retinal detachment was decreased to 64% in the treated eyes. (P = 0.002). The implantation of the scleral plug effectively inhibited intravitreous proliferation of fibroblasts. This study demonstrated that the scleral plug of biodegradable polymers may have potential as a treatment modality for PVR.

Animals↗
PubMed1995

Reduction in tumor formation on polyethylene by collagen immobilization.

After surface modification with collagen immobilization through covalent binding, porous polyethylene pieces were implanted subcutaneously into the back of rats for 1 year and the tumorigenesis-reducing effect was examined. In the virgin pieces without collagen immobilization, tumors were observed in 11 out of 24 pieces implanted (45.8%). On the other hand, in the collagen immobilized pieces a tumor was found only in one of 24 implanted pieces (4.2%). These results suggest that immobilization of collagen on the surface of an artificial material through covalent binding is very effective for a reduction of tumor formation.

Animals↗
PubMed1995

Immediately detachable coil for aneurysm treatment.

We developed an endovascular coil that is instantly detached by high-frequency electrical current. By applying the electrical current, a polyvinyl alcohol junction between the coil and the delivery wire is disrupted by heat within a second. This detachment system was shown to be reliable in the treatment of experimental aneurysms.

Animals↗
PubMed1995

Biodegradable plate fixation of rabbit femoral shaft osteotomies. A comparative study.

Femoral shaft transverse osteotomies in 58 rabbits were fixed with ultrahigh strength poly-L-lactic acid plates made by a drawing technique. Similar osteotomies in another 35 rabbits were fixed using stainless steel plates. The union rate, the mechanical strength of the united bones, bone mineral content and density in the area beneath the plate using dual energy x-ray absorptiometry, and the cortical thickness beneath and opposite the plate using a digitizer was compared between the poly-L-lactic acid and stainless steel groups after postoperative periods of 8, 25, and 40 weeks. The poly-L-lactic acid and stainless steel groups showed union rates of 67% (39 of 58) and 80% (28 of 35) without displacement, respectively. In the poly-L-lactic acid group, plate failure occurred in 14% (8 of 58). The mechanical strength of the specimen was restored to a level equal to that on the untreated side by 25 weeks, and cortical thickness and bone mineral content and density were maintained almost normal for 40 weeks in the poly-L-lactic acid group. The stainless steel group showed significantly lower mechanical strength and led to osteopenia because of stress shielding after 25 weeks.

Animals↗
PubMed1995

A new model of subretinal neovascularization in the rabbit.

PURPOSE: To establish a new model of subretinal neovascularization (SRN) in the rabbit by implanting basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres beneath the retina. METHODS: Basic fibroblast growth factor-impregnated gelatin microspheres were prepared by forming a polyion complex between gelatin and bFGF. The microspheres, containing 2.5 micrograms of bFGF, were injected into the subretinal space of rabbit eyes (n = 29). Control eyes (n = 10) received bFGF-free gelatin microspheres. Eyes were followed up for 3 days to 8 weeks by ophthalmoscopy, photography, fluorescein angiography, light microscopy, and transmission electron microscopy. RESULTS: Twenty of 24 experimental eyes (83%) showed fluorescein leakage from SRN 2 weeks after implantation of the bFGF-impregnated microspheres. This leakage continued for 2 to 6 more weeks. In striking contrast, control eyes showed no fluorescein leakage. Histologic examination revealed SRN in all the experimental eyes but in none of the control eyes. CONCLUSIONS: Subretinal implantation of bFGF-impregnated gelatin microspheres induces reproducible SRN in the rabbit.

Animals↗
PubMed1995

Tissue reaction of bioabsorbable ultra high strength poly (L-lactide) rod. A long-term study in rabbits.

Bioabsorbable ultra high strength poly (L-lactide) rods, which were developed for internal fixation of fractures, were fabricated using a drawing technique. These rods were implanted in the subcutaneous tissue and in the medullary cavity of rabbits to investigate tissue reactions to poly (L-lactide) and to study their degradation process. After 18 months, histiocytes were found, and their phagocytic activity continued for as long as 42 months, with maximum activity observed between 24 and 36 months after implantation. At 62 months after intramedullary implantation, the materials had been absorbed almost completely and were replaced by bone marrow cells, with only a small amount of residual tissue reaction. At 69 months after subcutaneous implantation, the materials had been absorbed completely without any scar formation. During degradation, no foreign body giant cells were found and osteolytic expansion caused by liquid degradable materials was not seen.

Animals↗
PubMed1994

Scleral plug of biodegradable polymers for controlled drug release in the vitreous.

We designed a new device, a scleral plug, that releases drugs into the vitreous after being implanted and fixed at the pars plana. Use of the plug for provision of doxorubicin hydrochloride was evaluated in rabbits. The scleral plug (8.5 mg) was made of poly(lactic-glycolic acid) (molecular weight, 40,000 daltons) containing 1% doxorubicin. Vitreous concentrations of doxorubicin were measured after the implantation. In vitro studies showed that the plug released 26% of the drug during 4 weeks. In vivo studies demonstrated that the concentration in the vitreous humor was maintained at a therapeutic range for longer than 4 weeks. No substantial toxic reactions were observed by electroretinographic and histopathologic evaluations. Our findings suggested that a scleral plug made of biodegradable polymers is a promising device for a controlled drug-release system in the vitreous.

Animals↗
PubMed1994

Biomaterials lubricated for minimum frictional resistance.

To improve the frictional characteristics of a biomaterial, the mechanical performance of a lubricated surface was studied. In vitro friction tests showed that the coefficient of dynamic friction of the lubricated surface was about 0.01 against rabbit bladder and the coefficient of static friction increased with the preload period. The efficacy of a lubricated cystoscope was evaluated by an in vivo test simulating cystoscope operation. The maximal and the total resistance force on the cystoscope model were found to decrease with the surface lubrication. Histological study revealed that urethral damage caused by rubbing with the cystoscope model was reduced by this lubrication technique. Presumably, prolonged retention of water on the lubricated surface region prevented tissue adhesion to the foreign material.

Animals↗
PubMed1994

Fibroblast growth on polymer surfaces and biosynthesis of collagen.

The growth and morphology of rat fibroblasts cultured on various polymer substrates, as well as their collagen biosynthesis, were studied. A clear difference in cell growth and cell morphology was observed among the substrates. The dependence of cell growth on the water contact angle of substrate was similar to that of the adhesion. Fibroblasts could proliferate at the highest rate and showed the highest-ordered morphology when cultured on the substrate with a contact angle around 70 degrees, which was also the most favorable for cell adhesion. The amount of collagen synthesized by total cells and of adsorption of the synthesized collagen to substrates were in good correlation with the cell growth dependence on the contact angle of substrate, whereas the collagen synthesis per cell was more active on the surfaces poor for cell growth than on the good ones. Cells on surfaces promoting active collagen synthesis had a round shape and clustered upon each other. The collagen-immobilized surface had nearly the highest cell adhesion, high cell proliferation, and high collagen adsorption among the substrates studied. In addition, the highest-ordered morphology and no lag time for proliferation were observed for the collagen-immobilized surface. These results indicate that the collagen-immobilized substrate provides the most favorable surface for cell growth at the initial stage.

Animals↗
PubMed1994

In vitro hydroxyapatite deposition onto a film surface-grated with organophosphate polymer.

To produce a bone-bonding polymer surface that is capable of inducing deposition of a hydroxyapatite (HA) layer in the body fluid, an organophosphate polymer was covalently immobilized onto a high-density polyethylene film by surface graft polymerization of a phosphate-containing monomer. The grafted film was immersed in simulated physiologic solution (SPS). The chemical composition and structure of the formed apatite layer as well as its bonding strength to the polymer surface were investigated. To distinguish the effect of phosphate groups on the deposition of apatite layer from the simple calcium absorption by the anion, a comparative study was done using a polyethylene film with surface immobilized carboxylic groups. Calcium phosphate deposition was observed on all the materials investigated, but the kinetics, composition, deposit amount, and bonding strength of the new phase were found to be significantly different among the modified materials, depending on the density and chemical nature of the surface immobilized ionic groups. It was found that the polymeric materials modified by surface graft polymerization of a phosphate-containing monomer produce a carbonated HA layer firmly bonded with the material upon immersion in SPS. Carboxyl groups in the grafted layer was not enough to activate bonding with the HA layer.

Acrylates↗
PubMed1994

Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice.

After intravenous (iv) injection of 125I-labeled poly(ethylene glycol) (PEG) with different molecular weights to mice, the radioactivity of the organs was measured to pharmacokinetically analyze the body distribution of PEG according to a two-compartment model. High molecular weight PEGs were retained in the blood circulation for a longer period than low molecular weight PEGs. The terminal half-life of PEG in the circulation extended from 18 min to 1 day as the PEG molecular weight increased from 6000 to 190,000. PEG tended to accumulate in the tissues/organs such as muscle, skin, bone, and the liver to a higher extent than the other organs, irrespective of the molecular weight. The time dependence of tissue accumulation was based on the vascular permeability. The results of pharmacokinetic analysis suggested that small PEG tended to freely translocate from the circulation to extravascular tissues and to return to the blood circulation again by diffusion, whereas large PEG translocated more slowly to extravascular tissues. Urinary clearance decreased with increasing PEG molecular weight, similar to the tissue clearance, whereas liver clearance increased with the increasing PEG molecular weight, after passing a minimum around the molecular weight of 50,000. PEG uptake by Kupffer cells was enhanced as the molecular weight became > 50,000.

Animals↗
PubMed1994

Experimental study and clinical use of poly(vinyl acetate) emulsion as liquid embolisation material.

A new material, an emulsion of poly(vinyl acetate) was experimentally developed and clinically used to overcome several disadvantages in currently used liquid embolisation materials. The emulsion microparticles, 0.3-0.7 microns in size, possessed cationic charge on the surface and hence aggregated immediately on contact with fluids containing anions. This inert polymer has the advantage that it does not induce a deleterious reaction in living tissue. Moreover, its medium is water and it is not adhesive, like the cyanoacrylates. Several concentrations of emulsion were injected into the renal arteries of dogs. For the investigation of tissue reactions and the possibility of recanalisation, the emulsion was injected into rats both subcutaneously and into the renal arteries. The renal artery injections in dogs showed adequate radiopacity and consistent complete occlusion. The lower the concentration of the emulsion, the smaller the arteries which could be occluded. Even at very low concentrations, however, venous occlusion did not occur. Histological study of the embolised rat kidney revealed no detectable damage in the vessel wall and no recanalisation for up to 6 months. The subcutaneously injected PVAc emulsion elicited mononuclear cell infiltration and gradual centripetal fibrosis, without any deleterious effect on the surrounding tissue. A cerebral arteriovenous malformation (AVM) was embolised using the material. Histology of the resected nidus showed findings similar to those in the animal experiments.

Adult↗
PubMed1994

Surface modification of polymers for medical applications.

Most of the conventional materials do not meet the demands required for both their surface and bulk properties when used as biomaterials. An effective approach for developing a clinically applicable biomaterial is to modify the surface of the material which already has excellent biofunctionality and bulk properties. This review article focuses on the surface modification of polymers by grafting techniques, which have long been known in polymer chemistry but are not yet widely applied to biomaterials. A grafted surface can be produced primarily either by graft polymerization of monomers or covalent coupling reaction of existing polymer molecules onto the substrate polymer surface. The major surface properties that should be modified include two kinds of biocompatibility. One is the surface property that elicits the least foreign-body reactions and the other is the cell- and tissue-bonding capability. In addition, physiologically active surfaces with, for instance, selective adsorbability may be required. Attempts to produce these biocompatible or biospecific surfaces by grafting techniques are briefly overviewed in this article.

Biocompatible Materials↗