Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 109 records · Page 6Linked to original sources

PubMed1998

Therapeutic effects of 5-fluorouracil microspheres on peritoneal carcinomatosis induced by Colon 26 or B-16 melanoma in mice.

The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5-FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p. tissues for a longer period of time with lower blood plasma concentrations than does an aqueous 5-FU solution and reduces toxicity. In this study, we evaluated the therapeutic effects of 5-FU-MS on peritoneal carcinomatosis in mice. Four days after an i.p. inoculation with Colon 26 or B-16 PC melanoma, 5-FU at 200 mg/kg was administered i.p. as 5-FU-MS or as an aqueous solution of 5-FU. 5-FU-MS extended the survival of mice bearing Colon 26 or B-16 PC melanoma significantly better than the equivalent dose of aqueous 5-FU solution.

Animals↗

PubMed1998

Comparison of bone regeneration in a rabbit skull defect by recombinant human BMP-2 incorporated in biodegradable hydrogel and in solution.

The objective of this study is to compare bone regeneration induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated into a biodegradable gelatin hydrogel with that by rhBMP-2 in aqueous solution. After treating rabbit skull defects of 6 mm diameter with the two rhBMP-2 dosage forms, both of them increased the bone mineral density (BMD) at the skull defects with implantation time to a significantly higher extent than a rhBMP-2-free aqueous solution and a rhBMP-2-free empty gelatin hydrogel (p < 0.05). There was no quantifiable difference in BMD between the two dosage forms of rhBMP-2. Histological examination revealed that the integrity of newly generated bone increased with the rhBMP-2 dose, irrespective of the dosage form. The bone defect was filled with regenerated bone 21 days after treatment.

Absorptiometry, Photon↗

PubMed1998

Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein.

Biodegradable hydrogels were prepared from gelatin by glutaraldehyde cross-linking for release matrix of recombinant human bone morphogenetic protein-2 (BMP-2). BMP-2 solution was impregnated into the dried hydrogels to prepare BMP-2-incorporating gelatin hydrogels. In the in vitro study, enhanced retention of BMP-2 was observed from the BMP-2-incorporating gelatin hydrogels after an initial burst of BMP-2 incorporated initially in the hydrogel. Following subcutaneous implantation of (125)I-labeled BMP-2-incorporating gelatin hydrogels in the back of mice, the radioactivity remaining in the hydrogels was measured to estimate the in vivo release profile of BMP-2. It was found that BMP-2 was retained in the hydrogels for longer than 30 days, whereas 99% of BMP-2 injected in the solution form was cleared from the injected site within one day, completely disappearing within 3 days. Ectopic bone formation studies demonstrated that BMP-2-incorporating gelatin hydrogels exhibited a more potent ability for bone induction than solution injection of BMP-2. This finding indicates that enhanced retention of BMP-2 is promotes its ability to induce ectopic bone formation.

Animals↗

PubMed1998

Complexation of basic fibroblast growth factor with gelatin.

Polyion complexation between basic fibroblast growth factor (bFGF) and gelatin was studied by the turbidity change of mixed solution, heparin high performance liquid affinity chromatography (HPLAC), and isoelectric electrophoresis. When an aqueous solution of acidic gelatin with an isoelectric point (IEP) of 5.0 was mixed with that of bFGF, the turbidity of the mixed solution increased with time, whereas basic gelatin with and IEP of 9.0 did not cause any solution turbidity. A maximum turbidity of the mixed bFGF and acidic gelatin solution was observed around a bFGF/gelatin molar ratio of 1.0, irrespective of the gelatin concentration and solution temperature. The solution turbidity decreased with an increase in the ionic strength of the mixed solution. Complexation of bFGF with acidic gelatin was slower than that with poly(acrylic acid) probably because of the lower density of gelatin negative charge than that of poly(acrylic acid). HPLAC study revealed that complexation of bFGF with the acidic gelatin reduced the affinity of bFGF for heparin, in contrast to the basic gelatin, although the extent became smaller with the increasing ionic strength of the solution. An electrophoretic experiment showed that the IEP of bFGF shifted to a lower value after its gelatin complexation. These findings indicate that an electrostatic interaction is the main driving force for the complexation between acidic gelatin and basic bFGF.

Acrylic Resins↗

PubMed1998

Application of biomedical engineering to neurosurgery.

Biomedical engineering is increasingly becoming very important also in neurosurgery. This article describes some examples of neurosurgical applications of biomaterials which play a central role in biomedical engineering. Since a large number of biomaterials are currently used in neurosurgery, only the biomaterials that have been developed in our laboratories in collaboration with neurosurgeons are briefly presented here. The biomaterials developed include devices used for interventional neurosurgery and bioabsorbable scaffolds for regeneration of dura mater and skull bone. We developed an immediately electrically detachable coil using a poly(vinyl alcohol) junction between the coil and the delivery wire. This is the first detachable coil developed in Japan and is currently under clinical trial. In addition to the coil used for interventional neurosurgery, the development of an embolic liquid is presented. As an alternative to allografts such as Lyodura, we developed a dural substitute from synthetic bioabsorbable polymers which are completely free from potential risk of latent virus infection. Finally, our experience in tissue engineering for skull bone regeneration using growth factors coupled with polymeric carriers is presented to demonstrate the promise of tissue engineering in the future.

Aneurysm↗

PubMed1998

[Development of a dural substitute for preventing prion diseases induced by grafting of freeze-dried human dura mater].

To provide a substitute for the dura mater a new bioabsorbable composite sheet was developed. This composite was composed of two L-lactic acid-epsilon-caprolactone (50:50) copolymer films and a poly (glycolic acid) nonwoven fabric. They displayed good mechanical properties and were 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. Any infection, cerebrospinal fluid leakage, evidence of convulsive disorders, significant adhesion to underlying cortex, and calcification was not noticed in any cases. In addition, the regenerated duralike tissue had a high pressure-resistant strength 2 weeks after implantation.

Animals↗

PubMed1997

Histologic and mechanical evaluation for bone bonding of polymer surfaces grafted with a phosphate-containing polymer.

A phosphate-containing polymer was covalently immobilized onto a polyethylene (PE) rod, a poly(ethylene terephthalate) (PET) thread, and a PET film by a surface graft polymerization technique, followed by immersion in calcium phosphate solution to deposit a thin hydroxyapatite (HA) layer on the modified polymer surfaces. The PE rod had a tapered shape, while the PET thread was fixed with clips after implantation, both to minimize the micromovement which may occur in bone. The PE rod was implanted through press-fitting in the femur of rat. Significant enhancement was observed for direct contact of the implant surface with a newly formed bone for both the grafted only and the further HA-deposited PE rods in comparison with the untreated PE at 4, 5, and 6 weeks after implantation. The rats implanted with the modified PET thread in the femur were sacrificed 3 and 6 weeks after implantation. Statistically significant differences were observed for the untreated versus the grafted plus HA-deposited rods at 6 weeks after implantation. To study the resorption of the deposited HA on the methacryloyloxyethylene phosphate-grafted surface, HA-deposited PET films were subcutaneously implanted in the back of rats. The deposited HA was rapidly resorbed within 3 weeks of implantation. These results suggest that the phosphate polymer chains grafted on the PE and PET surfaces effectively induced nucleation and growth of HA crystals. It seems likely that the thin HA layer additionally deposited in vitro onto the grafted PE and PET surfaces was resorbed rapidly and then promoted the growth of HA crystals in vivo.

Animals↗

PubMed1997

Studies on tumor-promoting activity of polyethylene: inhibitory activity of metabolic cooperation on polyethylene surfaces is markedly decreased by surface modification with collagen but not with RGDS peptide.

Tumor promotion activity of polyethylene (PE) was estimated in terms of the inhibitory potentials on the gap-junctional intercellular communication using the metabolic cooperation assay. The gap-junctional intercellular communication of test cells was inhibited on the PE film, but this inhibitory activity was markedly decreased when the surface of the PE film was immobilized with collagen. These results suggest that the in vivo tumor promotion activity of the untreated PE may be stronger than that of collagen-immobilized PE. On the other hand, surface modification with RGDS peptide, which is well known as the sequence of cell attachment domain in extracellular matrix proteins, did not reduce the promotion activity of PE film. In addition, neither modification with bovine serum albumin nor RGES peptide reduced the activity of PE film. These findings suggest that reduction of the inhibitory activity on gap-junctional intercellular communication by collagen immobilization is not simply due to improved cell adherence via the RGDS sequence but to some cell-cell recognition via collagen molecules essential for the gap-junctional intercellular communication.

Animals↗

PubMed1997

Ex vivo and in vivo evaluation of the blood compatibility of surface-modified polyurethane catheters.

Catheter model tubes were prepared from a medical-grade polyetherurethane and their outer surfaces modified by surface-graft polymerization of acrylamide and dimethyl acrylamide (DMAA). The surface-graft layer was characterized by means of dry staining, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy, and protein adsorption. Ex vivo evaluation for the blood compatibility of the surface-modified polyurethane was carried out using the polyurethane tube as an arterio-venous shunt between the carotid artery and the jugular vein of rabbits. When the surface density of grafted polymer was in the range of 10-30 microg/cm2, the in vitro adsorption of IgG exhibited a minimum value and platelet adhesion to the grafted polyurethane surface was insignificant, in marked contrast with that to the virgin (nonmodified) surface. The in vivo blood compatibility of polyurethane was evaluated by implanting the catheter tube in the inferior vena cava of rabbits from the femoral vein after ligation of a distal site of the exposed femoral vein. After remaining there for predetermined periods of time, the implanted catheters were taken out together with the veins of the rabbits that had been heparinized and sacrificed just prior to excision of the veins. After exchange of the blood in the veins for saline, the excised veins were opened by cutting longitudinally to inspect for clot formations on the surfaces of the implanted catheters. Occlusion of the inferior vena cava was not observed for any of the catheters, nor was there any apparent damage or microembolizations in the lungs and kidneys. Many small-sized clots were observed on the surfaces of the nonmodified polyurethane tubes after a 2-week implantation whereas the catheter surfaces grafted with DMAA polymer chains had a much smaller number of clots. When the blood compatibility of polyurethane surfaces was graded for relative evaluation from one (marked clotting) to five (no clotting) based on the size and number of the clots, the evaluation results were as follows: 3.1 (virgin, 2 weeks), 4.0 (grafted, 1 week), 4.1 (grafted, 2 weeks), and 3.5 (grafted, 1 month).

Acrylamides↗

PubMed1997

Ultrastructure of the interface between cultured osteoblasts and surface-modified polymer substrates.

Osteoblasts derived from rat bone marrow cells were cultured on surface-modified poly(ethylene terephthalate) films in the presence of ascorbic acid, beta-glycerophosphate, and dexamethasone. The surfaces employed for cell culture included the untreated hydrophobic surface and three modified surfaces possessing immobilized phosphate polymer chains, collagen molecules, and a thin hydroxyapatite-deposited layer. They all were produced by photo-induced graft polymerization with subsequent surface modifications of the graft chains. The ultrastructural morphology of the substrate/cell interfaces formed in in vitro osteoblast culture on these substrates was studied by transmission electron microscopy. The osteoblasts cultured for 1 week on the modified surfaces showed rough endoplasmic reticula rich in intracellular space and early matrix production in the extracellular space, irrespective of the surface chemistry. After 2 weeks of culture, osteoblasts exhibited active elaboration of extracellular matrix proteins, mostly composed of collagen, on all the surfaces. A remarkable result observed at this stage was direct deposition of an electron-dense, afibrillar layer of 180 nm thickness onto the surface having phosphate polymer chains. This layer became much more electron dense after 3 weeks of culture. Energy dispersive X-ray microanalysis revealed the presence of calcium phosphate in this layer. It was further found that the predeposited hydroxyapatite layer on the phosphate polymer-grafted surface promoted mineral deposition in the extracellular matrix that surrounded cuboid, osteocyte-like cells.

Animals↗

PubMed1997

Crosslinking of hyaluronic acid with water-soluble carbodiimide.

Hyaluronic acid (HA) was chemically crosslinked with a water-soluble carbodiimide (WSC) to produce low-water-content films when brought into contact with water. The crosslinking reaction was performed in two different ways; one was by using HA films and the other by casting HA solutions. Both methods produced water-insoluble HA films. The lowest water content of the crosslinked HA films subjected to swelling with water was 60 wt % at 37 degrees C, which was lower than any reported values. Infrared spectra of the crosslinked films suggested that intermolecular formation of ester bonds between the hydroxyl and carboxyl groups belonging to different polysaccharide molecules led to crosslinking. For comparison, pectin which possesses hydroxyl and carboxyl groups in one molecule, similar to HA, was subjected to crosslinking with WSC. The finding on pectin also supported ester formation between different polysaccharide molecules. The crosslinking of HA film with WSC in the presence of L-lysine methyl ester prolonged the in vivo degradation of HA film, probably because of amide bond formation as the crosslink.

Carbodiimides↗

PubMed1997

Nontoxic embolic liquids for treatment of arteriovenous malformations.

Interventional radiology is becoming one of the standard treatments of arteriovenous malformation (AVM). Cyanoacrylate derivatives and polymer solutions are widely used to occlude the AVM nidus by their injection through a catheter, but they are far from satisfactory embolic liquids. For instance, cyanoacrylate derivatives sometimes glue the catheter to the artery, resulting in serious complications; in addition, the organic solvents used to dissolve polymers cause damage to the surrounding brain tissue of the AVM. Therefore, we attempted to develop embolic liquids by dissolving poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) in Iopamiron with an addition of a small amount of ethyl alcohol. This new embolic liquid is not cytotoxic and is easily injected into the AVM through a thin, long catheter to effectively occlude the AVM.

Animals↗

PubMed1997

Intrathoracic tracheal reconstruction with a collagen-conjugated prosthesis: evaluation of the efficacy of omental wrapping.

Reconstructions of the intrathoracic trachea in 24 dogs were done with the use of 50 mm long collagen-conjugated tracheal prostheses. Omental wrapping was also done in 14 of the dogs (omentopexy group) to evaluate the efficacy of this option in comparison with results in the other 10 dogs (control group). All 24 dogs had uneventful postoperative courses and were killed at 4 weeks or 3, 6, or 12 months after the operation. Better epithelialization and fewer complications, such as mesh exposure and luminal stenosis, were observed in the omentopexy group than in the control group. Angiography and analysis of regenerated blood vessels revealed that vessel ingrowth had started within 4 weeks and that vessel formation reached its maximal point within 6 to 12 months in the omentopexy group. In contrast, revascularization of the subepithelial region in the control group was poor even after 3 months, and vessel formation continued for as long as 12 months. The differences between the two groups were considered to be mainly a result of the speed of blood vessel ingrowth into the regenerated mucosa. We conclude that our prosthesis can be used safely for intrathoracic tracheal reconstruction and that omental wrapping is a useful supplementary method that reduces the occurrence of complications.

Anastomosis, Surgical↗

PubMed1997

Preparation of cross-linked hyaluronic acid films of low water content.

Hyaluronic acid (HA) was chemically cross-linked with poly(ethylene glycol) diglycidyl ether, a diepoxy compound (EX-810), to yield low water content and slowly degradable films when brought into contact with water. The cross-linking reaction was performed under acidic and neutral conditions, since the epoxy group is readily hydrolysed in alkaline media. To allow the reaction to proceed at high HA concentrations, a solution casting method was employed for the cross-linking of HA. The lowest water content of the cross-linked HA films obtained was 60 wt% when swollen with buffered saline at 37 degrees C. Alginic acid and poly(vinyl alcohol), which possess hydroxyl groups, similar to HA, were also found to undergo cross-linking with the diepoxy compound. Since IR spectra of the cross-linked films had no significantly new absorption, intermolecular formation of ether bonds between the hydroxyl groups belonging to different polysaccharide molecules was assumed to take place. It seemed too difficult to detect the ether bonds in the cross-linked HA films, because the virgin HA film itself contained ether bonds in the molecule. The cross-linked HA film with a water content of 60 wt% exhibited practically no weight loss after 10 days of immersion in phosphate-buffered saline (pH 7.4), while this film underwent in vivo degradation by 30% weight loss after 7 days of subcutaneous implantation in rats. The inflammation reaction elicited around the implanted film was not significant.

Alginates↗

PubMed1997

In vitro and in vivo degradation of films of chitin and its deacetylated derivatives.

Chitin was deacetylated to various extents with NaOH to obtain partially and thoroughly deacetylated chitins. The specimens used in this study were deacetylated by 0 (chitin), 68.8, 73.3, 84.0, 90.1 and 100 mol% (chitosan). Films with a thickness of 150 microns were prepared from these specimens by the solution casting method. The equilibrated water contents of the films were 52.4 (chitin), 73.8 (68.8 mol%), 64.2 (73.3 mol%), 61.8 (84.0 mol%), 57.8 (90.1 mol%) and 49.7 wt% (chitosan), while the tensile strengths of the water-swollen films were 244 (chitin), 197 (68.8 mol%), 232 (73.3 mol%), 320 (84.0 mol%), 293 (90.1 mol%) and 433 g mm-2 (chitosan). The maximum water content and the minimum tensile strength observed for a specimen deacetylated between 0 and 68.8 mol% may be ascribed to the lowered crystallinity by deacetylation of chitin, since both chitin and chitosan are crystalline polymers. Unlike their physical properties, in vitro and in vivo degradations of these films occurred less rapidly without passing a maximum or minimum, as their degree of deacetylation became higher. The in vitro degradation was carried out by immersing the films in buffered aqueous solution of pH 7 containing lysozyme at 37 degrees C, while the in vivo degradation was studied by subcutaneously implanting the films in the back of rats. It was found that the rate of in vivo biodegradation was very high for chitin and 68.8 mol% deacetylated chitin, compared with that for the 73.3 mol% deacetylated chitin. The films which were more than 73.3 mol% deacetylated showed slower biodegradation. Interestingly, the tissue reaction towards highly deacetylated derivatives including chitosan was very mild, although they had cationic primary amines in the molecule.

Acetylation↗

PubMed1997

Microwave CO2 plasma-initiated vapour phase graft polymerization of acrylic acid onto polytetrafluoroethylene for immobilization of human thrombomodulin.

The functionalization of polytetrafluoroethylene (PTFE) for human thrombomodulin (hTM) binding has been achieved by CO2 plasma activation and subsequent vapour phase graft polymerization of acrylic acid (AA). The PTFE surfaces after CO2 plasma treatment, AA grafting and hTM immobilization were characterized by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and electron spin resonance (ESR) spectroscopy, as well as by zeta potential and wetting measurements to quantitatively control each step of modification. The activity of immobilized hTM was estimated by the protein C activation test.

Acrylates↗

PubMed1997

Synthesis of polylactides with different molecular weights.

The synthesis of poly(lactic acid) through polycondensation of the lactic acid monomer gave weight average molecular weights (Mw) lower than 1.6 x 10(4), whereas ring-opening polymerization of lactides in bulk at 130 degrees C for 72 h using stannous octoate as catalyst in the concentration range from 0.003 to 0.8 wt% produced polylactides with viscosity average molecular weight (Mv) ranging from 2 x 10(4) to 6.8 x 10(5). The monomer conversion and Mv showed a maximum at a catalyst concentration around 0.05 wt%. The monomer conversion and Mv increased almost linearly with polymerization time up to a monomer conversion of 80%, but both the conversion and Mv decreased after passing through a maximum, when the polymerization reaction was allowed to proceed for longer periods of time. This time dependence was pronounced at higher polymerization temperatures. The decrease in Mv at prolonged polymerization and higher polymerization temperatures was attributed to thermal depolymerization of resultant polylactides, but no significant optical rotation of poly(L-lactide) was noticed.

Biocompatible Materials↗

PubMed1997

Resorbable and non-resorbable augmentation devices for tenorrhaphy of xenografts in extensor tendon deficits: 12 week study.

Resorbable (poly-L-lactide) and non-resorbable (polyethylene terephathalate) tendon augmentation devices (TAD) in conjunction with a pericardial adhesion barrier, were designed to strengthen tenorrhaphies and were evaluated in an ovine extensor tendon deficit model in a short term study. Fifteen centimetres of tendon were resected and replaced with kangaroo tail tendon xenografts that had been cross-linked with 0.075% glutaraldehyde (GA) at 4 degrees C for one or seven days. Compared with tenorrhaphies performed with Kessler sutures alone, both types of TAD were more effective at preventing tenorrhaphy dehiscence, and thus maintaining tendon function. Furthermore, tensile strength of TAD tenorrhaphies increased significantly between zero and twelve weeks. For xenografts cross-linked in GA for one day, the tensile strength of tenorrhaphies with the resorbable TAD rose from 38 +/- 9 N at time zero, to 116 +/- 46 N at twelve weeks, while non-resorbable TAD tenorrhaphy strength at time zero was 42 +/- 16 N and 99 +/- 27 N at twelve weeks. For xenografts cross-linked with GA for seven days, similar increases in tensile strength of tenorrhaphies, with the two types of TAD were found. As there was no significant difference in mechanical performance or tissue response between the two TAD types in the first 12 weeks, use of the resorbable poly-L-lactide device may be advantageous clinically. Tensile strengths of midsections of the tendon xenograft cross-linked for 7 days was not significantly diminished 12 weeks after implantation and these xenografts were partially remodelled around the periphery. However, the tensile strength of xenografts cross-linked for one day declined significantly between time zero (319 +/- 80 N) and twelve weeks (239 +/- 92 N), suggesting that this degree of cross-linking was inadequate for maintenance of mechanical strength. Evaluation of the performance of tenorrhaphy augmentation devices with xenografts, over a longer implantation period, is required to further understand their usefulness for reconstruction of traumatic tendon injuries.

Animals↗