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Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 181 records · Page 10Linked to original sources

Protein permeation through poly(vinyl alcohol) hydrogel membranes.

Hydrogel membranes were prepared by radiation and chemical cross-linking of poly(vinyl alcohol) (PVA) in aqueous solutions. Effects of PVA concentration, PVA molecular weight and radiation dose, as well as concentration of cross-linking agent, in the case of the chemical cross-linking procedure, on the permeation of insulin, albumin and immunoglobulin (IgG) through the membranes were investigated. Glucose permeation was also studied. The cross-linking density affected the size of the macromolecular mesh of the hydrogel network and thus the water content of the membrane responsible for the diffusion of the solutes. The diffusion coefficient linearly increased for all the solutes with increasing water content in the PVA hydrogels, indicating that diffusion occurs primarily through the water hydrating the polymer network. The permeability study showed that the water content as well as the mesh size had an influence on the diffusion of low molecular weight glucose and insulin. Although the diffusion of higher molecular weight solutes, such as albumin and IgG, was not so much affected by the mesh size of elaborated PVA hydrogel membranes, the diffusion of these proteins was very low.

Albumins↗

Spacer effects on enzymatic activity of papain immobilized onto porous chitosan beads.

Papain was covalently immobilized onto the surface of porous chitosan beads without or with spacers of different lengths. The relative activity of the immobilized papain was found to be high toward a small ester substrate, N-benzyl-L-arginine ethyl ester (BAEE), but rather low toward casein, a high molecular weight substrate. Papain immobilized with spacer gave an almost constant activity, in marked contrast with the immobilized papain without spacer, whose activity monotonously decreased with decreasing surface concentration. The relative activity of the immobilized papain for hydrolysis of a high molecular weight substrate greatly depended on the length of the spacer. The pH, thermal and storage stabilities of the immobilized papain were higher than those of the free one, and ths papain immobilized directly to the chitosan beads' surface without any spacer gave a higher stability than those immobilized with spacer. The spacer's effect on the activity could be explained in terms of mobility of the immobilized papain molecule.

Arginine↗

Effect of polylactic acid on osteoinduction of demineralized bone: preliminary study of the usefulness of polylactic acid as a carrier of bone morphogenetic protein.

To evaluate the usefulness of polylactic acid (PLA), a bioabsorbable and plastic polymer, as a carrier of bone morphogenetic protein (BMP), a preliminary study has been carried out to investigate any negative effect of PLA on osteoinduction of demineralized bone (DB). PLA (10,600 mol. wt) was mixed with DB particles (1-1.5 mm square) prepared from rat femurs and laid subcutaneously on the intercostal muscle of 4-week-old Wistar rats. The PLA/DB pellets were harvested at 2, 4, 8 and 24 weeks after the operation, and prepared for light microscopic examination. Histological examination revealed cartilage formation at 2 weeks and new bone formation at 4 weeks. Extensive bone and marrow formation were observed at 24 weeks. PLA was gradually absorbed and completely disappeared at 24 weeks to be replaced by connective tissue. These results demonstrate that PLA does not have a negative influence on the osteoinductive activity and that PLA could well be a promising bioabsorbable carrier of BMP.

Animals↗

Poly(vinyl alcohol) hydrogels as soft contact lens material.

A new type of soft contact lens was developed from the poly(vinyl alcohol) (PVA) hydrogel prepared by a low temperature crystallization technique using a water-dimethyl sulfoxide mixed solvent. The PVA contact lens materials had a water content of 78% and a tensile strength of 50 kg/cm2, five times as strong as that of commercial poly(2-hydroxyethyl methacrylate) soft contact lens. The amount of proteins adsorbed to the PVA soft hydrogel material was half to one thirtieth of that of conventional soft contact lenses. Histological and scanning electron microscopic observation of rabbit eyes which had worn the PVA soft contact lens for 12 weeks showed no difference in corneal epithelium and cell arrangement in the corneal epithelium from the non-wearing eyes.

Adsorption↗

Fusogenic activity of various water-soluble polymers.

The fusogenic activity of seven water-soluble polymers was investigated using L929 cells in a monolayer state. Among these polymers, only two, poly(ethylene glycol) (PEG) and EPAN 680 were capable of inducing the membrane fusion of L929 cells. EPAN 680 is an ABA type block copolymer composed of 80% ethylene oxide(A) and 20% propylene oxide(B) sequences with a total molecular weight of 8800. Evaluation of the polymer hydrophobicity indicated that there was no clear correlation between it and the fusogenic activity of the polymer, although highly hydrophobic polymers caused cell shrinkage without membrane fusion. Differential scanning calorimetry on these polymers strongly suggested that hydration of the polymers in culture medium had a large effect on their fusogenic activity. It was concluded that the assembly of cell membranes, stabilized by water molecules, was disturbed by strong interaction with the polymer molecules having a strong hydration power, resulting in membrane fusion.

Animals↗

Clinical evaluation of uniaxially oriented poly-L-lactide rod for fixation of experimental femoral diaphyseal fracture in immature cats.

Transverse diaphyseal fractures of the femur were experimentally made in immature cats, and were fixed by an intramedullary pinning technique using an uniaxially oriented poly-L-lactide (PLLA) rod, a biodegradable polymer. The healing process was evaluated radiographically and histologically. Formation of bony callus was completed in 8 weeks, and cortical bony union followed. The remodeling process was then observed form 12 to 16 weeks. The healing process was almost the same as when a metallic implant was used. Abundant periosteal callus formation may be attributable to the lower elasticity of the PLLA rod compared with metallic implants. Since no other abnormalities such as growth deformities were detected, it was concluded that the combined use of a uniaxially oriented PLLA rod and an external splint is clinically useful for the repair of diaphyseal fractures in immature cats.

Animals↗

Application of oriented poly-L-lactide screws for experimental Salter-Harris type 4 fracture in distal femoral condyle of the dog.

The clinical usefulness of biodegradable oriented poly-L-lactide (PLLA) screws for experimental Salter-Harris type 4 fracture in the distal femoral condyle of dogs was evaluated. Bony union of the osteotomized fragment of the condyle was almost completed radiographically and histologically within 1 to 2 months after surgery, suggesting that PLLA screws maintained strength long enough to fix the fragment until bone healing. At 4 to 6 months after surgery, minute fissures were histologically confirmed on the surface of the screw thread, suggesting the early stage of biodegradation and absorption of the polymer. During the observational period, no significant difference between the treated femur and the contralateral non-treated femur in either total femoral length or maximum condyle width was observed, indicating no growth disturbance in the treated femur. From these results it was concluded that the PLLA screw might be an ideal implant for the reduction and fixation of epiphyseal plate fractures such as Salter-Harris type 3 or type 4 fractures.

Animals↗

Feasibility of drug targeting to the retinal pigment epithelium with biodegradable microspheres.

There are several systems of delivering drugs to cells with phagocytic activity. We studied the possibility of targeting drugs to retinal pigment epithelial (RPE) cells with the use of surface-modified microspheres. A fluorescent dye, 1,4-bis[2-(5-phenyloxazolyl)]-benzene (POPOP), was incorporated into microspheres of poly(lactic acid) for use as a marker to evaluate drug delivery. Phagocytosis of the microspheres, with or without gelatin precoating, was carried out at 37 degrees C and 4 degrees C. The cell-incorporated fluorescence of POPOP was measured, and scanning electron microscopy was used to confirm phagocytosis. At 4 degrees C, no uptake of POPOP was noted; however at 37 degrees C, cell-associated fluorescence was observed to increase for up to 24 hr. In comparison with bare microspheres, gelatin precoating significantly enhanced phagocytosis (P < 0.001) at the same incubation times. These results suggested that drug delivery to RPE cells may be feasible by means of surface-modified polymer microspheres.

Animals↗

In vitro phagocytosis of polylactide microspheres by retinal pigment epithelial cells and intracellular drug release.

We investigated phagocytosis of biodegradable microspheres containing a drug by retinal pigment epithelial (RPE) cells and drug release within the cells to evaluate the potential usefulness of microspheres for intracellular drug delivery. The biodegradable polymers used were L-lactic acid, and DL-lactic acid with different molecular weights or the copolymers of different monomer compositions. The microspheres containing a non-bioactive fluorescent dye (rhodamine 6GX) as a model drug, were prepared by a solvent evaporation method. The in vitro release of the dye from the microspheres was examined. Phagocytosis of the microspheres by RPE cells was conducted to evaluate the extent of phagocytosis by phase-contrast microscopy and transmission electron microscopy. The RPE cells ingesting the microspheres at different stages were examined by fluorescent microscopy to estimate the intracellular release of the dye. The dye was released with time from every microsphere and the release was controlled by changing the type of polymers constituting microspheres. The microspheres containing the dye were phagocytosed by RPE cells and the dye was released intracellularly with time. The present study indicates that the drug incorporated in the microspheres was delivered into RPE cells by way of phagocytosis and released within the cells. It is concluded that this microsphere system is a promising delivery form capable of drug targeting to RPE cells.

Animals↗

Effects of cross-sectional stress-relaxation on handling characteristics of suture materials.

Pullout friction and cross-sectional relaxation tests were conducted to quantitatively evaluate the handling characteristics of braided suture. The excellent handling of silk suture could be explained in terms of a large difference between static and dynamic pullout resistances. The difference in the resistance was closely correlated to the slope of the cross-sectional relaxation versus time logarithmic plot. It was therefore concluded that the cross-sectional stress-relaxation plays an important role in the handling performance of braided sutures.

Insect Proteins↗

Bioabsorbable struts made from poly-L-lactide and their application for treatment of chest deformity.

Poly-L-lactide, a polymer of lactic acid, shows slow degradation in living tissue. Poly-L-lactide plate of high molecular weight maintains more than 90% of its initial mechanical properties for more than 3 months after implantation. Using struts made from poly-L-lactide plate, we performed chest wall reconstruction in 56 patients: for postoperative chronic sternal dehiscence in 23 and sternal elevation for pectus excavatum in 33 cases. The postoperative external appearances of the anterior chest were improved in comparison with the preoperative state in all cases. The internal features were evaluated by computed tomographic scan. Neither postoperative wound infection nor respiratory complication was observed, and no tendency for regression of the anterior chest occurred in any of the patients. In 3 of 56 cases (5.4%; one in the sternal dehiscence group and two in the pectus excavatum group), it was necessary to remove part of the strut because of overgrowth of granulation tissue around the implanted material after 4, 12, and 13 postoperative months, respectively. In the pectus excavatum group, the computed tomographic evaluations showed that poly-L-lactide strut maintained sufficient strength to support the thoracic wall 5 months after implantation. These findings suggest that the bioabsorbable poly-L-lactide strut is a promising material for surgical treatment of chest deformity.

Absorption↗

Experimental study on a new tracheal prosthesis made from collagen-conjugated mesh.

A new tracheal prosthesis was made from fine Marlex mesh reinforced with a continuous polypropylene spiral. The mesh and spiral were covalently grafted and further coated with pig collagen with the aim of promoting connective tissue infiltration and providing initial airtightness. Complete surgical resection and replacement of a segment (2 cm in length, three to five tracheal rings) of the cervical trachea was performed in 13 adult mongrel dogs. Two dogs died of pneumonia about 2 months after operation, and eleven dogs were killed between 3 and 26 months. The prostheses in all dogs were promptly infiltrated by the surrounding connective tissue and completely incorporated by the host trachea. Formation of respiratory epithelium, which lined the prosthetic lumen, was seen to various degrees, and, in five dogs killed at 6 months or more after reconstruction, confluent epithelialization was confirmed histologically from the upper to the lower anastomotic site of the prosthesis. Marked stenosis of the prosthetic lumen caused by excessive scar tissue growth was seen in three dogs, and ulceration on the luminal surface was seen in two dogs. These results indicate that this tracheal prosthesis is highly biocompatible and promising for the repair of tracheal defects after further investigation.

Anastomosis, Surgical↗

A new vitreal drug delivery system using an implantable biodegradable polymeric device.

PURPOSE: The authors evaluated the feasibility of using an implantable biodegradable polymeric device to deliver drugs into the vitreous humor. METHODS: Two types of devices were prepared by compression-molding polymers of poly(DL-lactic acid) of two different molecular weights. The molecular weights of the poly(DL-lactic acid) used were 5,600 (device-1) and 9,100 (device-2). Sodium fluorescein (NaF) served as a hydrophilic drug marker. The release of the dye from the devices was studied in vitro. The intravitreal kinetics of NaF was evaluated in rabbits in vivo by fluorophotometry. The eyes were evaluated electrophysiologically and histologically to determine if there were toxic effects. RESULTS: Device-1 and device-2 released NaF for more than 25 and 45 days, respectively, in vitro. Detectable concentrations of NaF were present in the vitreous up to 17 days (device-1) and 28 days (device-2). Both types of devices were well tolerated, with no noted toxic effects. CONCLUSIONS: These results suggested that this device may be a potentially effective system to deliver drugs in the vitreous.

Animals↗

Pharmacologic effects of cisplatin microspheres on peritoneal carcinomatosis in rodents.

BACKGROUND: A new drug-delivery formulation of cisplatin, whereby cisplatin was incorporated in lactic acid oligomer microspheres (CDDP-MS), has been developed in dosage form for peritoneal carcinomatosis and has been designed to release 70% of the incorporated cisplatin slowly during a period of 3 weeks. In this study, its pharmacologic effects were examined in rodents. METHODS: CDDP-MS was tested to determine (1) tissue distribution of cisplatin after intraperitoneal administration of cisplatin at 3.0 mg/kg body weight to rats, (2) acute toxicity in mice when injected intraperitoneally, and (3) therapeutic effects on peritoneal carcinomatosis induced by transplantable M5076 tumors in mice. RESULTS: These experiments revealed the following: (1) CDDP-MS resulted in a higher cisplatin concentration in tissues adjacent to the peritoneum for a longer period, and the concentration of cisplatin measured in the rest of the body was lower than that delivered by the cisplatin aqueous solution; (2) the 50% lethal dose value, determined by the Litchfield-Wilcoxon method, was 23.8 mg/kg body weight in CDDP-MS in terms of cisplatin, whereas in the cisplatin aqueous solution it was 13.5 mg/kg body weight; (3) CDDP-MS enhanced therapeutic effects when compared with the same toxicity dosage of cisplatin aqueous solution. CONCLUSIONS: Intraperitoneal CDDP-MS releases cisplatin into the peritoneal cavity for a long time, and it results in less systemic toxicity and greater therapeutic effects on peritoneal carcinomatosis than does cisplatin aqueous solution.

Animals↗

Handling characteristics of braided suture materials for tight tying.

To establish criteria for characterizing synthetic sutures, the handling characteristics of silk suture were analyzed. The characteristics that distinguish silk suture from other braided suture materials are its good "knot security" and relatively low "tiedown resistance." Analytic consideration of knot security suggests that not only superficial friction but also resistance force produced by cross-sectional deformity of braided threads plays an important role in silk's superior performance. Results of a "pullout friction test," developed to quantitatively evaluate resistance produced by surface friction and cross-sectional deformity suggest that the superiority of silk thread can be explained in terms of high static withdrawal resistance under low loads and relatively low dynamic withdrawal resistance under high loads.

Elasticity↗

Porous polyurethane tubes as vascular graft.

A vascular graft with the inner diameter of about 3 mm was prepared from segmented poly (ether urethane) with an extrusion technique. To make the wall of the vascular grafts porous, NaCl salts were added to the polyurethane solution to be extruded and removed with water extraction after evaporating the solvent in the extruded tube. The wall was reinforced with elastic fiber to prevent dilation. The compliance of the vascular graft measured with the method of Hayashi et al. ranged from 0.2 to 0.3% mmHg -1. The initial Young's modulus was close to that of canine carotic artery, to which the porous polyurethane graft 4-cm long was anastomosed. Vascular grafts were occluded within 2 weeks after implantation, when their pore size was 0, 1.7, or 4.4 mum, whereas those with the pore size of 5.5, 7.4, and 30 mum were patent for longer than 4 weeks. When the vascular graft with the pore size of 30 mum was implanted for 6 months, the luminal surface was covered with neointima, but the endothelium-like cells appearing in the middle of the intima of the vascular graft were immature and sometimes had a very big nucleus. In addition, spindle-shaped, modified smooth muscle cells were noticed in the deep layer of the neointima, especially in the tissue where anastomotic intimal hyperplasia occurred.

Animals↗

Platelet deposition onto polymeric surfaces during shunting.

In an attempt to develop blood-contacting tubes that can be applied for short-term uses with a reduced heparin concentration or, ideally, without heparinization, we evaluated the blood compatibility of polymeric materials with a rabbit ex vivo shunt model. The shunt tubes employed were made of silicone, plasticized poly(vinyl chloride) (PVC), and segmented poly(ether urethane) (PU). In addition, two kinds of surface-modified tube were used: poly(vinyl alcohol) (PVA)-coated PVC and poly(dimethylacrylamide) (PDMAA)-grafted PU. The ex vivo shunt results correlated well with protein adsorption and platelet adhesion in vitro. The following order for the extent of platelet deposition was given, irrespective of the blood-contacting duration: PDMAA-grafted PU < PVA-coated PVC < PU < silicone, PVC. It is likely that many platelet aggregates detached from the PVA-coated PVC surface. For PDMAA-grafted PU, no trace of detachment of aggregates could be detected on any of the SEM photographs. The number and morphology of blood cells adhered onto the tube surfaces during ex vivo shunting were dependent on the kind of polymer surfaces, the blood exposure time, and the flow rate of blood.

Animals↗

Porous collagen sponge for esophageal replacement.

A new artificial esophagus with a bilayered structure made of porous collagen sponge and silicone was studied. The concept of this study was not to replace an esophageal defect permanently with prosthesis but to promote tissue regeneration by collagen. Five centimeters of cervical esophagus were replaced by this artificial esophagus in 19 adult mongrel dogs. Two weeks after implantation, the collagen sponge was replaced by autologous tissue and regeneration of the "neoesophagus" was observed in all animals. The inner surface of the neoesophagus was covered with mature mucosal epithelium similar to the intact esophagus 4-5 weeks after implantation. The replacement site was not complicated by infection, anastomotic leakage, or exuberant granulation tissue development on the luminal surface. In a long-term survival study, animals showed moderate-grade stenosis but could take normal feed orally and with no clinical problems observed.

Animals↗