Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Toll-like receptor (TLR)-mediated signalling plays a role in cerebral ischaemia/reperfusion (I/R) injury. Modulation of TLRs has been reported to protect against cerebral I/R injury. This study examined whether modulation of TLR3 with poly (I:C) will induce protection against cerebral I/R injury. Mice were treated with or without Poly (I:C) (n = 8/group) 1 hr prior to cerebral ischaemia (60 min.) followed by reperfusion (24 hrs). Poly (I:C) pre-treatment significantly reduced the infarct volume by 57.2% compared with untreated I/R mice. Therapeutic administration of Poly (I:C), administered 30 min. after cerebral ischaemia, markedly decreased infarct volume by 34.9%. However, Poly (I:C)-induced protection was lost in TLR3 knockout mice. In poly (I:C)-treated mice, there was less neuronal damage in the hippocampus compared with untreated I/R mice. Poly (I:C) treatment induced IRF3 phosphorylation, but it inhibited NF-κB activation in the brain. Poly (I:C) also decreased I/R-induced apoptosis by attenuation of Fas/FasL-mediated apoptotic signalling. In addition, Poly (I:C) treatment decreased microglial cell caspase-3 activity. In vitro data showed that Poly (I:C) prevented hypoxia/reoxygenation (H/R)-induced interaction between Fas and FADD as well as caspase-3 and -8 activation in microglial cells. Importantly, Poly (I:C) treatment induced co-association between TLR3 and Fas. Our data suggest that Poly (I:C) decreases in cerebral I/R injury via TLR3 which associates with Fas, thereby preventing the interaction of Fas and FADD, as well as microglial cell caspase-3 and -8 activities. We conclude that TLR3 modulation by Poly (I:C) could be a potential approach for protection against ischaemic stroke.

There has been a great interest in preparing polymeric reflective surfaces in the last few years. The application of supercritical fluid technology in this area is beginning to receive a great deal of attention. Poly ether ether ketone (PEEK) is well known for its excellent thermal, chemical, mechanical and electrical properties. These properties make it ideal for use in aerospace, electrical, fluid handling and coating industries. Supercritical infusion of a silver-containing additive (1,5-cyclooctadiene- 1,1,1,5,5,5-hexafluoroacetylacetonato)silver(I) into a PEEK film was achieved with moderately high density CO2 at various temperatures, pressures, and times. During the infusion process: 1) polymer sample was exposed to both supercritical CO2 and the additive under pressure for a brief time, 2) depressurization of the system caused the CO2 to rapidly diffuse out of the polymer; while the remaining additive in the polymer desorbed at a much slower rate governed by its diffusivity in the CO2-free polymer. Following this process the infused film was heated for a short time period to thermally reduce the infused metal and to form a reflective surface. In this research the effect of different additive concentrations, infusion conditions (e.g. temperature, pressure, time), and curing conditions (e.g. air flow rate, temperature, time) on the nature of the PEEK surface will be presented. / Master of Science

Enhancing the colloidal stability of nanoparticles dispersions, in order to extend the utilization time without any loss of performance, is desired. Prior works have confirmed the electrosteric stabilization of colloidal particles by so-called “amino-quat-primer” polymers, hyperbranched poly(ethylenimine) polymers containing amino groups and quaternized groups. In this work, a systematic investigation on the factors influencing the polymer-particle-interactions was carried out. Hence, aqueous silica-nanoparticle-dispersions were polymer-functionalized; their dispersions stability was studied using turbidity analysis; and the particle surface charge was examined employing electrophoretic measurements. Five key factors influencing the polymer-particle-interaction were defined, including: the polymer-particle-ratio, the degree of polymerization and the degree of functionalization of the polymer, the dispersion pH and the salt concentration. Alternatingly occurring areas of stable, unstable and again stable dispersions with an increasing polymer-particle-ratio occurred due to a charge reversal of bare, negatively charged to polymer-covered, positively charged particles. An additional area of unstable dispersions at very high polymer concentrations was assumed to arise from depletion forces of non-adsorbed free polymer. Stable, positively charged, polymer-covered silica nanoparticles were obtained for optimized conditions regarding the five key factors. After the dispersion stability enhancement, the new amino-functionalized surface could be used for further modifications, e.g. to result in a compatibility with a polymer matrix to fabricate highly functional polymer / inorganic hybrid materials.

Hollow fiber membranes (HFMs) formed through phase inversion methods exhibit specific physicochemical characteristics and generally favorable surface and mechanical properties, supporting their use in diverse applications including ultrafiltration, dialysis, cell culture, bioreactors, and tissue engineering. Characterization of, and modifications to, such membranes are important steps in achieving desired characteristics for specific applications. HFMs subject to gas, irradiation, and chemical sterilization techniques were characterized based on several analytical techniques. It was revealed that these common sterilization techniques can cause inadvertent changes to HFM properties. While these changes may cause detrimental effects to HFMs used in filtration, the methods of sterilization are also presented as a facile means of tuning properties toward specific applications. Modifications to HFM surface chemistries were also sought as a method of adsorbing bacterial lipopolysaccharide (LPS) from solutions used in hemodialysis treatments and bioprocessing applications. It was found that additives such as polyvinylpyrrolidone (PVP), polyethyleneglycol (PEG), and poly-L-lysine (PLL) can facilitate adsorption capacities of HFMs toward LPS. Additionally, chemical changes are presented as a means of preferentially adsorbing LPS to specific locations on the HFM surface.

Mechanical properties of (woven carbon fiber / vinyl ester matrix) composites can be greatly improved if the interphase between the reinforcing high-strength low-weight fiber and the thermoset resin is made more compliant. In order to improve the adhesion of the vinyl ester matrix to the carbon fiber, a thermoplastic coating such as poly(vinyl pyrrolidone) (PVP) can be used as an intermediate between the matrix and the fiber. The extent of mutual diffusion at the (sizing material / polymer matrix) interphase plays a critical role in determining the mechanical properties of the composite. In this research, the molecular interdiffusion across a poly(vinyl pyrrolidone))/vinyl ester monomer (PVP/VE) interface is being investigated by Fourier Transform Infrared Attenuated Total Reflectance (FTIR-ATR) spectroscopy. The ATR method which can be used to characterize the transport phenomena, offers several advantages, such as the ability to monitor the diffusion <I>in situ</I> or to observe chemical reactions. In order to separate the effects of the vinyl ester monomer diffusion and the crosslinking reaction, ATR experiments were carried out at temperatures below the normal curing temperature. Diffusion coefficients were determined by following variations in infrared bands as a function of time, and fitting this data to a Fickian model. The values of the diffusion coefficients calculated were consistent with values found in the literature for diffusion of small molecules in polymers. The dependence of diffusion coefficients on temperature followed the Arrhenius equation. Hydrogen bonding interactions were also characterized. The diffusion model used in this study, however, does not seem to be appropriate for the particular (PVP/VE) system. Because the glass transition temperature of the PVP changed as diffusion proceeded, one would expect that the mutual diffusion coefficient did not stay constant. In fact, it was shown that the Tg can drop by 140oC during the diffusion process. A more suitable model of the (PVP/VE) system should take into account plasticization, hydrogen bonding, and especially a concentration dependent diffusion coefficient. Further analysis is therefore needed. / Master of Science

High molecular weight poly(phenylene sulfide sulfone) (PPSS) homo- and statistical copolymers have been reproducably synthesized using a known, but complex procedure utilizing 4,4'-dichlorodiphenyl sulfone (DCDPS), sodium hydrosulfide, sodium hydroxide, sodium acetate, and deionized water, in NMP at elevated reaction temperatures and pressure. The effect of these variations, e.g., reaction temperatures and times, molar ratios of H2O-to-NaSH, NMP-to-H2O, etc. were investigated. Optimized conditions were defined, which produced Tg as high as 222°C, very high refractive index (1.70), and tough/solvent resistant films could be prepared by melt fabrication. A two-stage decomposition mechanism in air was demonstrated by dynamic thermal gravimetric analysis. The melt stability of PPSS was improved by incorporating thermally stable endgroups, such as diphenyl sulfone, 4-chlorophenylphenyl sulfone, and t-butylphenoxide. The chemical structures of the endgroups were confirmed by 13C and 1H NMR spectra. Compared with mercaptide endcapped PPSS, the new systems showed higher initial degradation temperatures (2% and 5% weight loss), higher char yield at 650°C in air and a more stable melt viscosity at 300°C. A greatly simplified synthesis of both homo and copolymers has been successfully developed using the new A-A or A-B type thiol-functional monomers, such as bis-(4-mercaptophenyl) sulfone, 4-chloro-4'-mercaptodiphenyl sulfone and 4-chloro-4'-mercapto benzophenone, instead of sodium hydrosulfide. A series of high molecular weight triphenyl phosphine oxide and/or diphenyl ketone containing PPSS copolymers were subsequently synthesized from the bis-(4-mercaptophenyl) sulfone by reaction with 4,4'-dichlorodiphenyl sulfone, bis-(4-fluorophenyl) phenyl phosphine oxide, and 4,4'-difluorobenzophenone in DMAc in the presence of K2CO3 at 160°C. The new phosphine oxide containing PPSS copolymers were completely amorphous, showed improved solubility in common organic solvents and exhibited very high char yields in air at 750°C. Surface (XPS) analysis results suggested that the phosphorus moieties in the polymer backbone can form phosphate-like layers on the polymer surface which protects the inner materials from further decomposition in air at high temperatures. The diphenyl ketone containing PPSS copolymers showed very high char yields at 750°C in a nitrogen atmosphere, compared to sulfide sulfone homopolymer and phosphine oxide containing copolymers, possibly because of higher bond energies. Semi-crystalline poly(phenylene sulfide ketone) homopolymers and sulfone containing copolymers with sulfone/ketone mole ratio (S : K) < 25 : 75 were synthesized by a novel base catalyzed self-polycondensation of 4-chloro-4'-mercaptodiphenyl sulfone and/or 4-chloro-4'-mercapto benzophenone in N-cyclohexyl-2-pyrrolidinone (CHP) at 290°C. Amorphous copolymers with S : K ratios > 25 : 75 were prepared in DMAc at 160°C. These materials exhibited an increase in glass transition temperature with increasing sulfone content. TGA and micro cone calorimetry analyses showed that the semi-crystalline materials with high ketone content had much higher char yields and significantly lower heat release rate and total heat release, compared to the poly(phenylene sulfide sulfone) and poly(pheylene sulfide) controls. / Ph. D.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / A variety of polymers of synthetic origins (e.g., poly(ethylene glycol) or PEG) and naturally derived macromolecules (e.g., silk fibroin or gelatin) have been explored as the backbone materials for hydrogel crosslinking. Purely synthetic hydrogels are usually inert, covalently crosslinked, and have limited degradability unless degradable macromers are synthesized and incorporated into the hydrogel network. Conversely, naturally derived macromers often contain bioactive motifs that can provide biomimicry to the resulting hydrogels. However, hydrogels fabricated from a single macromer often have limitations inherent to the macromer itself. For example, to obtain high modulus PEG-based hydrogels requires an increase in macromer and crosslinker content. This is associated with an increase in radical concentration during polymerization which may cause death of encapsulated cells. Pure gelatin (G) hydrogels have weak mechanical properties and gelatin undergoes thermo-reversible physical gelation. Covalent crosslinking is usually necessary to produce stable gelatin hydrogels, particularly at physiological temperatures. The limitations of these hydrogels may be circumvented by combining them with another macromer (e.g., silk fibroin) to form hybrid hydrogels. Silk fibroin (SF) from Bombyx mori silkworms offers high mechanical strength, slow enzymatic degradability, and can easily form physical hydrogels. The first objective of this thesis was to evaluate the effect of sonication and the presence of synthetic polymer (e.g., poly (ethylene glycol) diacrylate or PEGDA) or natural macromer (e.g., gelatin) on SF physical gelation kinetics. SF physical gelation was assessed qualitatively via tilt tests. Gelation of pure SF solutions was compared to mixtures of SF and PEGDA or G, both with or without sonication of SF prior to mixing. The effect of gelatin on SF gelation was also evaluated quantitatively via real time in situ rheometry. Sonication accelerated gelation of SF from days to hours or minutes depending on SF concentration and sonication intensity. Both PEGDA and G were shown to accelerate SF physical gelation when added to SF and sonicated SF (SSF) solutions. The second objective was to develop a simple strategy to modulate covalently crosslinked PEG-based hydrogel properties by physically entrapping silk fibroin. The physical entrapment of silk fibroin provides an alternative method to increase gel storage modulus (G’) without the cytotoxic effect of increasing macromer and crosslinker concentration, or altering degradation kinetics by increasing co-monomer concentration. The effect of SF entrapment on gel physical and mechanical properties, as well as hydrolytic degradation and chemical gelation kinetics were characterized. SF physical crosslinking within the PEG-based network was shown to increase gel storage moduli by two days after gel fabrication. There was no change hydrolytic degradation rate associated with the increased moduli. SF entrapment did not affect gelation efficiency, but did alter gel physical properties. The third objective of this thesis was to develop a silk-gelatin in situ forming hybrid hydrogel for affinity-based growth factor sequestration and release and in vitro cell culture. SF provides mechanical strength and stability, whereas G contains bioactive motifs that can provide biomimicry to the gel network. Hydrogel G’ and its dependency on temperature, SF processing conditions, and secondary in situ chemical crosslinking (i.e., genipin crosslinking) were studied. Gelatin can be conjugated with heparin, a glycosaminoglycan, to impart growth factor (GF) binding affinity. Growth factor sequestration and release were evaluated in a pair of designed experiments. The hybrid gels were evaluated as substrates for human mesenchymal stem cell proliferation.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20412号 / 工博第4349号 / 新制||工||1674(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 杉野目 道紀, 教授 松田 建児, 教授 澤本 光男 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21115号 / 工博第4479号 / 新制||工||1696(附属図書館) / 京都大学大学院工学研究科物質エネルギー化学専攻 / (主査)教授 辻 康之, 教授 近藤 輝幸, 教授 中村 正治 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM