Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 199 records · Page 11Linked to original sources

PubMed1993

Tissue reactions to subcutaneously implanted, surface-modified silicones.

To evaluate the influence of surface properties on tissue reactions, the surface of a medical-grade silicone elastomer was modified without changing the bulk properties. Surface modifications employed were oxidation by corona discharge in air, graft polymerization of water-soluble monomers, coating a polysaccharide through polyion complex formation, and covalent immobilization of cell-adhesive proteins. Surface-modified silicone sheets were implanted in the subcutaneous tissue of rats, and tissue reactions such as infiltration of inflammatory cells, appearance of foreign-body giant cells, and collagenous capsule formation were studied. It was found that the thickness of collagenous capsules formed after 16 weeks' implantation was in the range of 85-95 microns for the nontreated ones and all the modified silicones except the acrylic acid-grafted and the collagen-immobilized silicones.

Animals↗

PubMed1993

Protein adsorption and platelet adhesion onto polyurethane grafted with methoxy-poly(ethylene glycol) methacrylate by plasma technique.

Graft polymerization of methoxy-poly(ethylene glycol) methacrylate, an ester of methacrylic acid and monomethoxy-poly(ethylene glycol) (PEO), was performed onto a polyetherurethane (PU) film and tube under different polymerization conditions by a plasma treatment technique. The surface of grafted PU film was characterized by staining with dye, x-ray photoelectron spectroscopy, contact angle, and zeta potential. All these measurements indicated that water-soluble chains were immobilized on the PU surface, their location being restricted to the film surface region. The PU surface showed reduced protein adsorption in vitro and reduced platelet adhesion in vitro and ex vivo. The optimum graft density suppressing the protein adsorption was as low as 5 micrograms cm(-2). When a small amount of dimethacrylate was added to the monomer solution for graft polymerization to introduce crosslinking in the grafted layer, protein adsorption was further slightly reduced. The extent of reduction in serum albumin adsorption was always less than that of gamma-globulin. Although platelet adhesion was largely reduced by the surface graft polymerization, a definite amount of protein was always adsorbed to the grafted surface.

Adsorption↗

PubMed1993

Introduction of functional groups onto the surface of polyethylene for protein immobilization.

Amino and carboxyl groups could be introduced onto the surface of high-density polyethylene film by utilizing graft polymerization of acrylamide and the subsequent Hofmann degradation and alkaline hydrolysis of grafted polyacrylamide. Graft polymerization was carried out by immersing an argon-plasma treated film in an aqueous solution of the monomer, followed by heating after degassing the monomer/film mixture. The surface density of these functional groups could be increased up to 10(-7) mol/cm2. The surfaces having amino and carboxyl groups exhibited positive and negative zeta potentials, respectively, when contacted with KCl aqueous solution. Both of the functional groups introduced onto the polyethylene surface were found to be utilizable for covalent immobilization of protein using carbodiimide for the carboxylic group or mediators such as glutaraldehyde and ethylene glycol diglycidyl ether for the amino group.

Acrylic Resins↗

PubMed1993

Soft tissue reaction to collagen-immobilized porous polyethylene: subcutaneous implantation in rats for 20 wk.

Collagen-immobilized porous polyethylene, in which the immobilization was through covalent bonding, and virgin porous polyethylene were implanted subcutaneously in rats from 1 to 20 wk. The results were the ingrowth of the connective tissue into collagen-immobilized porous polyethylene was rich and contained a low level of inflammatory cellular infiltration compared with that of virgin porous polyethylene. The material-tissue interface showed that the living body-originated collagen fibres were firmly anchored into the immobilized collagen layer. These results suggested that covalent immobilization of collagen on to the biomaterial surface is useful in promoting the ingrowth of soft tissue and the tissue adhesion.

Animals↗

PubMed1993

Study on the efficacy of biodegradable poly(L-lactide) mesh for supporting transplanted particulate cancellous bone and marrow: experiment involving subcutaneous implantation in dogs.

Poly(L-lactide) (PLLA) mesh sheets, monofilaments and mesh cylinders filled with fresh autogenic particulate cancellous bone and marrow (PCBM) were implanted subcutaneously into the back of 22 adult dogs for 1 yr. Polypropylene (PP) was used as a control. The inflammatory response to PLLA mesh sheets was slight, similar to PP mesh sheets. However, 3 months after implantation, histiocytes and multinucleate giant cells appeared on the surface of the monofilaments of PLLA mesh sheets and gradually increased in number as the monofilaments were degraded and absorbed. Almost no inflammatory cellular infiltration was seen in the tissue around PLLA mesh sheets or between the monofilaments. When a PLLA mesh cylinder filled with PCBM was implanted subcutaneously, the bone formation reached its peak 1 month after implantation, as in the case of a similar PP mesh cylinder, and bone formation was observed along the inner wall of the cylinder. In addition, a vascular net was abundant within the cylinder. The mechanical strength of the test material (PLLA monofilaments) did not change for almost 2 months after implantation, and 80% of its initial strength was retained for 3 months. These observations suggest that a PCBM graft supported by PLLA mesh would be very effective in the reconstruction of damaged maxillofacial bones, since histological tissue reactions associated with biodegradation of the PLLA mesh are mild and the PLLA mesh does not interfere with bone formation of PCBM. It was also found that the PLLA mesh retains its mechanical strength long enough to allow the PCBM transplant to develop sufficient strength to sustain the damaged region.

Animals↗

PubMed1993

Trypsin immobilization on to polymer surface through grafted layer and its reaction with inhibitors.

Trypsin was covalently immobilized and physically adsorbed on to the surface of poly(ethylene terephthalate) fibres using poly(acrylic acid) (PAAc) chains grafted on to the ozonized fibres. The covalent immobilization was accomplished through amide formation between amino groups of trypsin and carboxyl groups of grafted PAAc chains, with the use of water-soluble carbodiimide. A set of samples with surface concentrations of grafted polymer ranging from 0.03 to 2.5 micrograms/cm2 was used to study the effects of grafted layer on the enzymatic activity of immobilized trypsin and its inhibition by trypsin inhibitors of different molecular sizes. The amount of immobilized trypsin increased linearly with an increase in graft yield of fibres, but the activity of immobilized enzyme reached saturation at a certain graft yield, probably because of diffusion limitation for the transport of enzyme substrate molecules into the grafted PAAc layer. The reduction of inhibition with an increase in graft yield and in molecular weight of inhibitors was attributed to enhancement of steric hindrance and enzyme inactivation in the dense grafted layer. We also found that the adsorbed trypsin was inhibited more easily than the covalently immobilized at any concentration of the grafted PAAc and for any type of inhibitor used.

Acrylic Resins↗

PubMed1993

Polyurethane surface modification by graft polymerization of acrylamide for reduced protein adsorption and platelet adhesion.

Surface modification of polyurethane by glow-discharge treatment and subsequent graft polymerization of acrylamide was studied. The modified hydrophilic surfaces were characterized by the measurements of dynamic contact angle and zeta potentials and examined for protein adsorption behaviour and platelet adhesion. Data from in vitro and ex vivo experiments indicated a reduction of protein adsorption and platelet adhesion for the hydrophillic graft polymers, the extent of which was correlated to polymer graft density.

Acrylamides↗

PubMed1993

Re-freeze dried bilayer artificial skin.

A bilayer artificial skin composed of a silicone sheet and a collagen sponge sheet was developed by us in 1986, modifying Yannas and Burke's technique. It was used in experimental animals and clinically, both with success; but the artificial skin was inconvenient for clinical use in terms of disinfection and preservation. In an attempt to reduce the drawbacks, we developed a re-freeze dried artificial skin. Experiments were conducted to examine whether the re-freeze dried material is equivalent to the prototype one. A significant difference between the two was found in tensile tests but not in experimental and clinical effects.

Adult↗

PubMed1993

Reduction in tumour formation on porous polyethylene by collagen immobilization.

After surface modification with collagen immobilization through covalent bonding, porous polyethylene pieces with an average pore size of 400 microns were implanted subcutaneously into the back of rats for 1 yr. It was found that connective tissues with abundant blood vessels were formed clearly, filling more than 90% of the pore volume and bound firmly to the pore walls. A tumour was found in only one of 24 implanted pieces (4.2%). On the other hand, the virgin porous polyethylene pieces without collagen immobilization exhibited inflammatory reactions within the pores and the connective tissues produced filled only 15% of the pore volume. Formation of a malignant histiocytoma was observed in 11 of the 24 pieces which had been implanted (45.8%). Thus, immobilization of collagen on the surface of an artificial material through covalent bonding proved to be very effective not only for firm bonding with soft connective tissues but also for a reduction of tumour formation.

Animals↗

PubMed1993

Application of poly(L-lactic acid) particles for the suppression of genetic resistance to bone marrow allografts by reticuloendothelial system-blockade.

We have recently successfully achieved bone marrow allografts by reticuloendothelial system (RES)-blockade. Long-term survival of the recipient mice after BMT was achieved without apparent evidence of graft-versus-host disease (GVHD), although T-cells were not depleted from donor marrow cells. Hemopoietic system of these recipient mice was replaced by that of donor origin [7]. As a first step to the application of this technique for human patients, we tested poly(L-lactic acid) (PLLA) particles as biodegradable particles. PLLA particles were phagocytized by macrophages when injected intravenously, and degraded slowly. PLLA has already been in clinical use as a bioresorbable suture material and matrix for drug release. We found that administration of PLLA prior to bone marrow transplantation resulted in a successful take of the allografts. In addition, PLLA was found not to show any antigenicity in normal mice.

Animals↗

PubMed1993

Potentiation of in vivo antitumor effects of recombinant interleukin-1 alpha by gelatin conjugation.

Chemical conjugation of a recombinant human interleukin-1 alpha (IL-1) with gelatin was conducted using a water-soluble carbodiimide in an attempt to augment the indirect effect of IL-1 on in vivo tumor cell growth in mice. Chromatographic studies of the IL-1-gelatin conjugate demonstrated that the apparent molecular weight of IL-1 was increased by the gelatin conjugation and about 60% of IL-1 activity was retained in the prepared conjugate. Intraperitoneal (i.p.) injection of the conjugate significantly suppressed the intraperitoneal growth of a subline of Meth A fibrosarcoma cells (RR1 cells), compared with the effect of free IL-1 at the same dose, although the cells per se were resistant not only to free IL-1 but also to gelatin-conjugated IL-1. Simple mixing of gelatin with free IL-1 did not augment the in vivo antitumor effect as compared with that of free IL-1. Gelatin conjugation improved the in vivo stability of IL-1. Prolonged retention of IL-1 activity in the peritoneal cavity as well as the circulation of mice was observed after i.p. injection of the IL-1-gelatin conjugate in comparison with free IL-1 injection, irrespective of the presence of tumor cells. Gelatin conjugation was effective in augmenting the in vivo antitumor effects of IL-1 to activate host cells, e.g. macrophages (M phi). The i.p. injection of the conjugate enhanced M phi infiltration into the peritoneal cavity of tumor-bearing mice and peritoneal M phi were strongly activated to inhibit the in vitro growth of RR1 cells. Thus, gelatin conjugation was effective in augmenting the indirect effect of IL-1 via host cells, leading to a high suppressive effect on in vivo growth of tumor cells.

Animals↗

PubMed1993

Suppressive effect of recombinant TNF-gelatin conjugate on murine tumour growth in-vivo.

A recombinant human tumour necrosis factor alpha (TNF) was conjugated to gelatin by means of carbodiimide to improve the in-vivo stability of TNF. About 55% of TNF activity was retained after gelatin conjugation as judged by the cytotoxicity assay using L-M cells in-vitro. Intraperitoneal injection of the TNF-gelatin conjugate significantly suppressed the in-vivo growth of murine Meth A fibrosarcoma cells (SS2 cells) in mouse peritoneum, in comparison with that of free TNF at the same dosage (P < 0.05). After intraperitoneal injection, TNF activity of the conjugate was detected in both the serum and the peritoneal cavity of mice for a longer period than was free TNF, irrespective of the presence of SS2 cells. Chromatographic studies of the conjugate demonstrated that the increase in the apparent molecular weight of TNF was consistent with gelatin conjugation. It is likely that this leads to a prolonged retention of TNF activity in-vivo. In addition, the TNF-gelatin conjugate suppressed the in-vitro growth of SS2 cells to the same extent as free TNF. Thus, it is possible that the longer retention period of the conjugate brought about an increase in the chance of contact between TNF and SS2 cells, resulting in the enhanced suppressive effect of TNF on in-vivo tumour cell growth. Gelatin conjugation is an effective method for increasing the in-vivo antitumour activity of TNF.

Animals↗

PubMed1992

[The effect of nicardipine on angiogenesis in vitro].

We studied the effect of nicardipine, a calcium channel blocker, on the morphological change of endothelial cells in vitro. Cultured endothelial cells derived from bovine carotid artery make tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9)-10(-5) M of nicardipine in a dose dependent manner. Migration of endothelial cells was also suppressed by the same dose of nicardipine. However, proliferation of endothelial cells was not enhanced. These findings suggest that nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells.

Animals↗

PubMed1992

Toxicity test of biodegradable polymers by implantation in rabbit cornea.

To evaluate whether or not the corneal micropocket implantation is effective for determining the toxicity of polymeric materials, currently used biodegradable polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), LA-GA copolymers, and three kinds of poly(2-cyano-acrylate)s (PCA) were implanted in a rabbit corneal pouch and the tissue responses were observed macroscopically and microscopically. It was found that PLA induced no vascularization, whereas a residual solvent and ethylene oxide gas remaining in the PLA matrix invoked vascularization. Vascularization clearly took place when PGA was implanted in the cornea, which became opaque, probably because of cellular infiltration. In the case of PCA implantation, severe inflammation as well as vascular invasion occurred in the initial stage. It is likely that these tissue reactions were caused by the leachables from the implanted materials, the extent being dependent on the leaching rate and the toxicity. It was concluded that the corneal micropocket assay is a good means to detect trace amounts of leachables from implanted materials without sacrificing the animals with the implanted materials.

Animals↗

PubMed1992

In vitro and in vivo studies on bioabsorbable ultra-high-strength poly(L-lactide) rods.

Ultra-high-strength poly(L-lactide) (PLLA) rods were fabricated using a drawing technique. Rods with a diameter of 3.2 mm and a draw ratio of 2.5:1 showed initial bending strength and modulus values of 240 MPa and 13 GPa, respectively. The purpose of this study was to investigate the in vitro and in vivo degradation of PLLA rods with a draw ratio of 2.5:1. The greater the rod diameter, the longer the bending strength was maintained in phosphate buffered saline at 37 degrees C. The bending strength retention of rods (diam. 3.2 mm) implanted in the subcutis of rabbits was almost equal to that of rods in the in vitro study, while those rods implanted in the medullary cavity of rabbit femora showed a slightly lower bending strength retention. Molecular weight was reduced to the greatest extent in the medullary cavity, followed by in the subcutis and in vitro. The weight of PLLA rods in the medullary cavity was reduced by 22% at 52 weeks and by 70% at 78 weeks after implantation. Histologically, no inflammatory or foreign body reaction was observed in the medullary cavity for 52 weeks. The drawn PLLA rods maintained a bending strength exceeding that of human cortical bone in the medullary canal for a period of 8 weeks, suggesting that the drawn PLLA rods may be useful in the repair of fractured human bones.

Absorption↗

PubMed1992

In vitro and in vivo digestion of collagen covalently immobilized onto the silicone surface.

In order to study the in vivo digestion of immobilized collagen and gelatin, these proteins labeled with 125I or fluorescein isothiocyanate (FITC) were covalently immobilized onto silicone surfaces, which were grafted with acrylic acid to introduce carboxyl groups, and implanted subcutaneously in rats and mice. When the proteins were labeled with FITC, the amount of proteins immobilized decreased with the increase of the number of FITC molecules conjugated with the protein molecule. In the wet state, FITC conjugated with the proteins was less stable than 125I. Approximately half of the amount of the immobilized proteins was digested in vivo within the first week and until 5 weeks after implantation the proteins were gradually digested. At that time, the amount of the proteins remaining on the silicone surface ranged from 0.6 to 1.0 microgram/cm2, which was several times larger than the amount of an assumed monolayer adsorption of proteins. Even after 15 weeks, the amount of proteins remaining on the silicone was almost the same as after 5 weeks. No significant difference in digestion was observed between collagen and gelatin, regardless of the labeling agent. Because of less stability and easier handling of FITC and higher stability and more difficult handling of 125I, FITC seems more suitable for short-term and 125I for long-term studies.

Animals↗

PubMed1992

Tissue reactions induced by modified poly(vinyl alcohol) hydrogels in rabbit cornea.

The purpose of this study was to compare the tissue reactions induced by modified poly(vinyl alcohol) (PVA) hydrogels with other materials implanted in the rabbit cornea. PVA hydrogels with and without covalently bonded collagen were compared to ethylene-vinyl alcohol copolymer, and polysulfone discs. These materials were implanted in the rabbit corneal stroma. The resultant tissue reactions were histologically and clinically studied. The PVA hydrogels had high flux rates of glucose and L-lactic acid in vitro. Covalent immobilization of collagen onto their surface was found to render them more biocompatible. However, excessive ulceration and vascularization of the cornea still occurred in vivo, possibly because of extremely little blinking of the rabbits, which might cause desiccation of the cornea.

Animals↗

PubMed1992

Interactions of poly(ethylene glycol)-grafted cellulose membranes with proteins and platelets.

The interactions of proteins and platelets with cellulose membranes grafted with poly(ethylene glycol) were studied. The poly(ethylene glycol) grafting was carried out using poly(ethylene glycol)-monoacid and poly(ethylene glycol)-diacid, which have one and two terminal carboxyl groups, respectively. The grafting operates through esterification between the carboxyl groups of poly(ethylene glycol) and the hydroxyl groups on the membrane surface. Both of the poly(ethylene glycol) grafted membranes reduced the complement activation. Adsorption of bovine serum albumin and gamma-globulin increased when the membrane was grafted with poly(ethylene glycol)-diacid, but did not change when it was grafted with poly(ethylene glycol)-monoacid. When platelets were incubated with serum proteins, the platelet adhesion to the membranes slightly decreased by grafting both the poly(ethylene glycol)-diacid and poly(ethylene glycol)-monoacid. The poly(ethylene glycol)-diacid grafted surface showed more clotting than the poly(ethylene glycol)-monoacid grafted and original surfaces.

Animals↗