The effect of mobile molecular chains on cell attachment and growth was studied using ethylene-vinyl alcohol copolymer films surface-modified with various types of mobile molecular chains. Hydrophobic and water-insoluble mobile molecular chains with low glass transition temperatures, such as polyoxypropylene, polyoxytetramethylene and polydimethylsiloxane, had no apparent effect on cell attachment and growth. Only the water-soluble molecular chain like polyoxyethylene, which has high mobility in water and high excluded volume effect, exhibited significant effects; they lowered cell attachment. Cell behavior toward polyoxyethylene chains attached with hydrophobic groups varied considerably depending on the type of hydrophobic groups and on the balance between those groups and the hydrophilic chains. Aromatic rings promoted cell attachment.

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Adhesion of rat hepatocytes was enhanced strikingly by incubating them in cell-culture dishes whose surface had been coated with a homopolystyrene derivative having a pendant lactose residue in each repeating unit. Several oligosaccharide-containing polymers were prepared from glucose, maltose, lactose, and maltotriose as starting meterials; aqueous dilute solutions of these polymers were incubated on glass and polystyrene dishes to adsorb the polymers on the surface; a suspension of hepatocytes was added to the polymer-coated dishes. Coating with lactose-containing polymer (PVLA) markedly facilitated the adhesion of hepatocytes. This cell-adhesion was a threshold phenomenon: there was littile adhesion until a critical PVLA concentration (-10^-4mg/ml) was reached, and increasing the concentration above this value permitted maximal adhesion. These findings were discussed on the basis of the specific interaction between hepatocytes and non-reducing _D-galactose residues, the latter of which were present in every structural units of PVLA and functioned as the recognition determinant for hepatocytes.

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In order to obtain fundamental information about the effect of substrate on cell adhesion and growth and about the relationship between them, poly (γ-benzyl-_L-glutamate) (PBLG) was chemically modified to introduce cationic or anionic sites. These chemically modified PBLGS were coated on glass dishes by solvent casting method. Adhesion and growth of mouse established fibroblast (mouse L) on these polymer-coated dishes were estimated. Mouse L adhered strongly to poly (α-amino acid) s containing cationic sites. Growth of mouse L was very good on unmodified PBLG or its derivatives containing moderate amount of cationic or anionic sites. In case of cationic or anionic poly (α-amino acid) s anyhow, excess charge inhibited the normal growth of mouse L. It was suggested that moderate amount of net charges on poly (α-amino acid) s were important for cell growth.

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In order to obtain fundamental information on the biomedical properties of tri-block copolymers containing poly (α-aminoacid), A-B-A type tri-block copolymers consisting of poly (β-benzyl-_L-aspartate) as the A component and poly (ethylene oxide) or poly (dimethyl siloxane) as the B component have been prepared by the polymerization of the β-benzyl N-carboxy-_L-aspartate anhydride using the middle block component with primary-amine groups at both ends as initiator. Molecular weight distributions of samples are in the range of 1.1-1.4 as determined by gel-permeation chromatography. It is indicated that the A block component in A-B-A block copolymers takes α-helical conformation. From the results of cell culture experiments using HeLa S3 cells, the cell adhesiveness of block copolymers with poly (ethylene oxide) as middle block component is low but that of block copolymers with poly (dimethyl siloxane) as middle block component is as good as that of poly (β-benzyl-_L-aspartate). Thus A-B-A type tri-block copolymers containing of poly (β-benzyl-_L-aspartate) as the A component are promising as substrate for cell culture or cell separation by changing the middle block components.

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In order to clarify how structures of fibrin are related to cellular attachment and how polymer materials affect cellular responses and fibrin structures, the responses of fibroblast (adhesion, growth and morphological changes) to fibrin fiber gel coated on sulfonated-polystyrene with varied negative charges were examined. It was found that negative charges on sulfonated-polystyrene surface affected fibrinogen-fibrin conversion, changed structures of fibrin gel formed on sulfonated-polystyrene and furthermore changed cellular responses. The results offer us fundamental informations about biomaterial design of artificial skin and artificial vessel.

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Physicochemical properties of fluoridated apatites and mechanical properties of composite containing theapatites as filler were examined. Fluoridated apatites synthesized at 80°C and pH 7.4 showed unexpectedcrystallinity phenomena with the increase of the degree of fluoridation. Their solubility decreased dramaticallyat very low fluoride concentration. The apatites were mixed with 2, 2′-bis (4-methacryloxydiethoxypheny1) -propane. BPO and DHPT were used as polymerization initiators. The compressive strength and Knoophardness of the composites increased with the increase of apatite content below apatite-resin ratio, A_p/R, of 2 and should little dependence on the degree of fluoridation. The thermal expansion coefficient of thecomposite with A_p/R=1 was almost equal to that of teeth. In tooth cavities, the composites seemed toadhere well to enamel without a bonding agent.

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New phenol methacrylates with hydrophobic and hydrophilic groups were synthesized by the reaction of methacrylic acid with p-substituted phenylglycidyl ethers. Their effectiveness on the adhesion to tooth enamel was evaluated. The adhesiveness depended on hydrophobic groups and the tensile strength increased in the following order: -OMe<-H<-Cl<-Me<OPh. 2-Hydroxy-3- (p-phenoxyphenoxy) propyl methacrylate (Pho HPPM) showed the highest adhesive strength.

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Visible light curing resins were prepared by dissolving methacryloyl fluoride (MF) -methyl methacrylate (MMA) copolymer in monomer liquid consisting of MMA and triethylene glycol dimethacrylate (3G). The photopolymerization ability of the experimental resins was enhanced with increasing 3G content in the monomer mixture. The measurement of adhesive strength of the experimental resins to human or bovine enamel revealed that the strong adhesion could be obtained by etching the enamel surface for 1 min with 65% phosphoric acid. The adhesive strength to bovine enamel after 60 thermal cycles at 4 and 60°C was shown to be 4.6-6.8 MPa. The amount of fluoride ions released when the cured resins were immersed in phosphate buffer solution was determined. The release rate of fluoride ions was above 0.07%/day even after 164 days, although the rate decreased slightly with the lapse of time. The results suggest that the experimental resins should be suitable for long-term release of flouride ions in oral cavity.

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Acoustic emission (AE) characteristics under the tensile shear bond strength were measured in order to evaluate the structural adhesive bonding for tooth substances of two commercial chemical-cured composite resins. Initial generation of AE in the structural adhesive bonding of composite resins for human enamel and dentin showed 30 to 40% and 50 to 70% of their tensile shear bond strengths, respectively. The microfracture of both structural adhesive bondings initiated from a low or middle stress region of their bond strengths. Composite resins had about twice more high the tensile shear bond strength to enamel than that to dentin and had the difference of about 8 MPa in tensile shear bond strength to enamel, as compared with that to dentin, but the difference in initial generation of AE for both adherends was under 1 MPa. Therefore, it can be concluded that the acid etch technique to enamel surface increased the tensile shear bond strength and exhibited a ductile and tough deformation-fracture behavior, but caused little rise in initial generation of AE.

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Composites were prepared by mechanical mixing of bioabsorbable poly (lactic acid) s (PLA) with a hydroxyapatite (HA) powder at temperatures above their softening points to give composites with different PLA/HA ratios. The PLA used were _{D, L-} and _L-lactic acid oligomers with M_w ranging from 2, 000 to 7, 000. SEM observation of the fractured surface of the composites revealed good compatibility between PLA and HA. Both the softening point and the flow point of the composites were increased with the increasing HA portion in the composite. A similar improvement was observed for the impact and compressive strength, which were enhanced with increasing molecular weights of PLA. Ca⁺⁺ was found to elute due to degradation of HA in the course of hydrolytic degradation of the composites in vitro, probably because degradation of PLA resulted in a slight decrease in the pH of the medium. Implantation of the composites into the excised osseous tissue of rats showed that new bone tissue formation occurred in correspondence with the absorption of the composites. The complete absorption of the composites took place at 8 weeks after implantation. The above observations suggest that the PLA-HA composites may have clinical applications as a bone filler.

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Poly (N-hydroxyalkyl _L-glutamine) hydrogels were prepared by carrying out arninoalcoholysis reaction of poly (γ-benzyl _L-glutamate) (PBLG) membranes with aminoalcohols, , such as 2-amino-1lethanol (E), 3-amino-1-propanol (P), or 5-amino-l-pentanol (Pe), together with crosslinking reaction with octamethylene diamine (OMDA). The reactions between their bulk structures and their membrane properties, such as the swelling in water, water vapor permeability, tensile properties, and enzymatic degradation behavior of the membranes in PECF solution were studied. The effective crosslink density was shown to be proportional to the percent of crosslinker (OMDA) in the reaction mixture. The tensile properties of hydrogels were highly dependent on the degree of swelling of PECF, Q_w, and on the hydrophobicity of the side chains, whose behavior was typical of an elastomer. A common relation was obtained for the rates of water per meability, V_f, and Q_w of sample, in spite of the difference of the nature of side chains. Biodegradation of samples in vitro by pronase indicated that the degradation could be regarded as a bulk rather than a surface phenomenon. The rate of degradation, V (1/2), was also highly dependent on Q_w of samples, as well as on the hydrophobicity of side chains of samples.

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Some random _DL-alanine-containing copolymers, such as _DL-alanine [Ala] and β-ethyl-_L-aspartate [Asp (OEt)] and _DL-alanine [Ala] and γ-ethyl-_L-glutamate [Glu (OEt)] were prepared according to N-carboxy α-amino acid anhydride (NCA) methods. They were then melted by heating under a pressure of 150 kg/cm² to obtain the columnar matrices (1.6 mm in diameter) which have high density and rigidity. The 100% in vivo degradation of melt-pressed copolymer matrices were observed in compositions more than 50 mol% Ala for [AlaAsp (OEt)] _n and 75 mol % Ala for [AlaGlu (OEt)] _n After a melt-pressed [AlaAsp (OEt)] _n (50 mol% Ala) was irradiated for 3 h at a dose rate of 1×10⁶ rad/h at temperatures of -196, -78, 0, 30, and 60°C, in vacuo with γ-rays from a ⁶⁰Co source, the in vivo degradations when they were implanted subcutaneously in the back of rats during the first 3 weeks period were 33.6%, 29.5, 18.9, 52.5, and 22.4%, respectively. Thus the in vivo degradation of the above matrix has the maximum value at around 30°C. Such a tendency was observed also in a [AlaGlu (OEt)] _n matrix. The differences in the in vivo degradation of Ala-containing copolymer matrices owing to the irradiation temperature were investigated from such data as viscosity and amino acid analysis. The viscosity (η_6p/c) of a melt-pressed [AlaAsp (OEt)] _n (50 mol% Ala) irradiated at a temperature of 0°C rapidly decreased with an increase in the irradiation dose (1×10⁵ rad to 1×10⁷ rad: 0.50 dl/g to 0.13 dl/g), though it gradually decreased at 30°C (1 ×10⁵ rad to 1×10⁷ rad: 0.53 dl/g to 0.33 dl/g). In this case, the in vivo degradation of melt-pressed matrix irradiated at 0°C decreased with an increase in the irradiation dose. On the contrary, the in vivo degradation of melt-pressed matrix irradiated at 30°C showed a remarkable increase with increasing irradiation dose. The data of amino acid analysis showed that the digestion of Ala moiety in a [AlaAsp (OEt)] _n (50 mol% Ala) irradiated at 30°C is slightly faster than that at 0°C.

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The relationships between aggregation states of hard segments in segmented poly (urethaneureas) and fatigue behavior after lipids sorption are reported. The SPUU used in this study consists of hard and soft segments. The soft segment is composed of poly (tetramethylene glycol) (PTMG) with number average molecular weight of M_n and 4, 4′-diphenylmethane diisocyanate (MDI). The hard segment consists of MDI and various diamines. The temperature dependences of infrared spectra and dynamic viscoelasticity revealed that the aggragation of hard segment is stronger for the hard segment consisted of MDI-ethylenediamine (EDA) (Biomer ®) or MDI-1, 2-propylenediamine (PDA) (TM M_n) than for the one consisted of the random sequence of MDI-EDA and MDI-4, 4′-diaminodiphenylmethane (DAM) (TU M_n). The degree of phase mixing between the hard and soft segments in TU M_n is more extensive than that in TM M_n. The specimen after immersing in lipids solution showed weight increase due to lipids sorption. The amount of increase in weight after lipid sorption was larger for TU M_n than for TM M_n. Also, the temperature dependences of dynamic viscoelasticity of the specimen after imersing in lipids solution revealed that disordered hard segments of TU M_n lost their aggregation strength after lipids sorption. The fatigue strength of TU M_n after lipids sorption decreased extensively and showed the formation of microcracks near fatigue fracture surface. This is attributed to the adsorbed lipid. However, TM M_n and Biomer did not show reduction of fatigue strength after lipids sorption. These results indicate that SPUU with disordered hard segments loses its fatigue strength in a biological environment.

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Some kinds of water-soluble cellulose derivatives and methacrylic acid copolymers have been known as the enteric film coating of medical tablets. Using newly developed hydroxypropyl methylcellulose acetate succinate derivatives (HPMCAS) as samples, the rate of solution of the sample films were measured in various buffer solutions in order to make clear the dissolution mechanism, such as the pH dependence of dissolution and disintegration for coated tablets. The dissolution time of the films became shorter with increase of pH values at pH larger than 5 and reached almost constant value around pH=7-8, indicating that on strong acidic conditions (pH<5) the dissolution of films did not occur. Potentiometric titration measurements of HPMCAS samples were also carried out.
It becomes clear that a factor governing the rate of solution and solubility of HPMCAS sample films is the electrostatic free energy of dissociation of carboxyl groups.

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Tablets were prepared from powder of pullulan, a water soluble polysaccharide, by direct compression, and the following dissolution behavior in water was observed. Pullulan dissolved gradually from the surface of tablet as the contained drug released at close to constant rate (0-order) depending on the molecular weight of pullulan, but independent of the pH of test solvent. The dissolution can be controlled by simple processing of tablets. Along with the facts of simple preparation and safety for human bodies, these results suggested that pullulan tablets can be used for sustained release of drugs. Then, many kinds of tablets were prepared from pullulan mixed with other polymers, i. e., starch, cellulose fine powder, and cellulose derivatives used in medicines. Dissolution behavior of most of these tablets was similar to that of pullulan tablets. The results of in vivo experiments using a dog indicated sustained release of sulfamethizole from tablets prepared from high molecular weight pullulan and from a mixture of pullulan and hydroxypropylmethyl cellulose.

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Mixing of pullulan and other polymers was further studied in order to prolong the dissolution of pullulan tablets. Pullulan and small amount of konjac glucomannan were mixed dissolving both polymers in water and then co-precipitating. Tablets prepared from the mixed powder dissolved very slowly in water. Dissolution behavior of the tablets and release of drugs from the tablets were investigated using various preparations of mixtures. Although the mechanism may be different from that of pullulan tablets, release from the tablets of the mixtures was also close to 0-order. Dissolution rate depends on the content of glucomannan and other factors, suggesting some possibility for controlled release. Partially degraded glucomannan was applicable. Other gums were examined; it was found that polysaccharides of heteromannan were similarly effective in mixing with pullulan. Since the preparation is simple and the materials are inactive against living bodies, mixtures of pullulan and heteromannans are expected to be utilizable practically for sustained release systems of drugs.

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Dissolution rates of some practically water-insoluble drugs: phenytoin (PT), indomethacin (IM) andgriseofulvin (GF): roll-mixed with polyvinylpyrrolidone K-30 (PVP) were investigated in comparison withthose of coprecipitates and physical mixtures. Each drug roll-mixed with PVP exhibited its predominantdisselution rate in the range of 8 to 50% of PVP content. The maximal disselution rate of the drugs wasclearly superior to that of the coprecipitates. Drug crystals of PT and IM were readily changed to anamorphous state by roll-mixing procedures as the PVP content increased, although a few of the crystals ofGF still remained even at the PVP centent of 84%. PVP in the roll mixing system stimulated dissolutionof the drugs PT and IM; these were readily converted to an amorphous state by roll-mixing progedure.

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Styrene-glycidyl methacrylate copolymer (I) microspheres were prepared by an emulsifier-free emulsion polymerization technique. The enzymatic activity of trypsin adsorbed onto these microspheres was investigated to examine the fitness of the surface as a carrier of enzymes. An increase in surface hydrophilicity of the microspheres was the result of an increase in surface glycidyl group content. This was accompanied with a small decrease in the amount of adsorbed trypsin, and a remarkable increase in the specific activity. In the case of carboxylated (I) microspheres, the weak acid charge density on the surface increased along with an increase in the amount of adsorbed trypsin and resulted in the enhancement of the total activity.

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Dialdehydestarch coated with gelatin (DAS-gelatin) was modified by reacting urease with remaining aldehyde groups on DAS surface (DAS-gelatin-urease) to remove urea fast from uremic patients. DAS binds ammonia much faster than urea. Immobilized urease on DAS did not show the enzimatic activity. On the other hand DAS-gelatin-urease possessed the activity and could hydrolyze urea to ammonia which was removed by the DAS component within one hour. It could treat urea nearly two times more than DAS-gelatin. In vitro studies suggested that DAS-gelatin, on oral uremic treatment, removed ammonia in gastrointestinal tract. DAS-gelatin-ureas was inactivated at pH 1.2 and it became unnecessary to immobilize urease to DAS-gelatin for oral administration. DAS-gelatin could be a good carrier for the immobilization of bioactive peptides.

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Plasma polymerization was applied as the technique of wettable treatment on silicone rubber (SR) contact lens (CL) surface and discussed about the possibilities of application for CL. A homemade apparatus was equipped with electric source of 13.56 MHz and outer electrode of capacity load. Vinylpyrrolidone (NVP) was selected as monomer in consequence of some experiments related with the durability of polymerized layer and the observation of its surface states. The best suitable conditions of polymerization were 40 watt, 0.1 to 0.2 torr and 60 seconds. The plasma polymerized layer was able to tolearate for drying at room temperature, boiling into water and rubbing at CL cleaning.
The new CLs exchanged by wettable trouble was only 2.3% among all worn CLs in clinical test, and most of the trouble CLs had the surface contaminated by tear components (example for protein, lipid, mucin, etc.).
It was considered that the plasma polymerized layer with NVP was superior to the surface treatment on SRCL.

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