Synthesis of organosilicon-containing macromonomers through an anionic polyaddition reaction

Lithium diisopropylamide (LDA) induces metalation reaction of 4-(trimethylsilylmethyl)-styrene (SMS) to form lithiated SMS (SMSLi). SMSLi initiates the anionic polymerization of SMS to form oligomers with a polymerizable vinyl end-group. Mechanistic studies revealed that the propagation proceeds mainly by the addition reactions of SMSLi to the double bond of preformed oligomers in the early stage of the polymerization. In the later stage of the polymerization, propagations between preformed oligomers take place concurrently. The extent of polyaddition enchainments in the oligomers was found to increase when the reaction was carried out keeping the monomer concentration as low as possible. Reactivities of the organosilicon-containing macromonomers were also estimated by UV, MO calculations, and radical homopolymerization.     

Novel perylene-containing polymers

Novel perylene-containing polymers have been synthesized. They exhibit good solubilities in organic solvents and have good film forming properties. A water-soluble perylene-containing polyimide was obtained via sulfonation of the corresponding polyimide. Solubilities and spectral characteristics of these polymers are discussed as a function of their structures.     

Novel fluorescent oxygen indicator for intracellular oxygen measurements

Intracellular oxygen concentration is of primary importance in determining numerous physiological and pathological processes in biological systems. In this paper, we describe the application of the oxygen sensing indicator, ruthenium dibipyridine 4-(1"-pyrenyl)-2,2'-bipyridine chloride [Ru(bpy-pyr)(bpy)(2)], for molecular oxygen measurement in J774 murine macrophages. Ru(bpy-pyr)(bpy)(2) exhibits strong visible absorption, efficient fluorescence, long excited state lifetime, large Stokes shift, and high photo- and chemical stability. The fluorescence of Ru(bpy-pyr)(bpy)2 is efficiently quenched by molecular oxygen. It is 13 fold higher in a nitrogenated solution than in an oxygenated one. The dye passively permeates into cells and maintains its oxygen sensitivity for at least 5 h when the cells are stored in a phosphate buffered saline solution at pH 7.4. The oxygen sensitivity, photostability, and chemical stability of the indicator and the effect of hypoxia and hyperoxia on the intracellular oxygen level in single macrophages are discussed.     

Novel sulfur-containing ferrocene polymers

Ferrocene-containing polymers were synthesized via addition reaction of 1,1′-dimercaptoferrocene ( 1 ) and 1,1′-bis(2-mercaptoethyl)ferrocene ( 2 ) to various diolefinic monomers such as dimethacrylates, divinyl ethers, divinyl sulfones and others. The dithiol 1 was also used as a monomer in condensation reactions with bifunctional acid chlorides. The polymerization of propylene sulfide in the presence of 1 as a bifunctional initiator was found to lead to polymers with a single central ferrocene unit.     

Novel membrane for guided bone regeneration

Membranes have been clinically used for guided tissue and bone regeneration for decades, but their use in every day clinical practice is rather limited. We developed a biodegradable membrane (InionGTR) composed of polylactide, polyglycolide and trimethylene carbonate aiming to improve the properties of membrane. Before application the membrane is treated with N-methyl-pyrrolidone (NMP) to achieve a rubber like consistency, to allow easy handling and manageability in the clinical setting. After placing the membrane NMP diffuses out from the polymer phase into the water phase. The loss of NMP in the polymer stiffens the membrane up and allows space maintenance in the defect area. In addition the influx and efflux of NMP creates a porous surface on the membrane leading to an improved integration of tissues into the porous surface layers of the InionGTR membrane. Therefore, the use of NMP improves the handling in the clinical setting, and allows tissue integration and space maintenance, both important for the outcome of the treatment.     

Novel alginate-acrylic polymers as a platform for drug delivery

The aim of the present work was to develop a family of novel materials based on a combination of sodium alginate and acrylic polymers and to evaluate their potential in drug delivery applications. In the presence of sodium alginate, acrylic chains with acidic as well as basic moieties were polymerized to create an interpolymer complex based on electrostatic interactions that are able to modulate the release rate of low molecular weight drugs. The synthesized materials were used to prepare hydrophilic matrices for drug delivery and tested for their adhesion properties to glass, used as a model substrate for mucoadhesion.     

Novel method for fabricating capillary membrane oxygenators

Operating problems associated with existing capillary membrane oxygenators have been impaired CO₂ removal, nonuniform tube perfusion, thrombus formation in the blood manifolds (headers) and fall-off in performance with scale-up of small units. These faults are primarily due to poor tube ventilation, inadequate control of tube lengths, and ineffective header design. A novel semiautomatic fabrication technique is described that minimises or eliminates these deficiencies. The technique produces a well ventilated tube bundle by accurately spacing the tubes within the potted end-sections (tube sheet). The tube sheet is 10–12 mm thick, about one half of that in previously described units. To give uniform tube perfusion and eliminate stagnant regions over the tube sheet, blood is introduced normal to the tube axis through headers of hemitoroidal configuration. Three oxygenators with different dimensions and flow capacities were testedin vitro andin vivo. Good agreement was obtained between the theoretically predicted and experimentally measured oxygen-transfer rates for all units, no loss in performance being shown with oxygenator scale-up. After canine partial-bypass of six hours duration, thrombus formation was minimal in the headers with only 1 per cent of the tubes being occluded. Further optimisation is possible with smaller-diameter capillaries.     

Solution and membrane properties of zwitterionic polymers

The aqueous solution properties of poly(4-vinylpyridinium sulfopropylbetaine) (PVPyPS, systematic name: poly{1-[1-(3-sulfonatopropyl)pyridinium-4-yl]ethylene} ( 1 )) and poly(3-methacryloylethoxycarbonylpyridinium sulfopropylbetaine) (PMAPS, systematic name: poly{1-methyl-1-[2-[1-(3-sulfonatopropyl)pyridinium-3-ylcarbonyloxy]ethoxycarbonyl]ethylene} ( 2 )) are investigated. Polymers 1 and 2 are soluble only in salt solutions and their intrinsic viscosity increases with increasing salt concentration, this being a common property of poly(sulfobetaine)s. Hydrogel membranes containing PVPyPS are opaque in pure water but become transparent in salt solution.     

Novel biodegradable electrospun membrane: scaffold for tissue engineering

Nonwoven fibrous matrixes have been widely used as scaffolds in tissue engineering, and modification of microstructure of these matrices is needed to organize cells in three-dimensional space with spatially balanced proliferation and differentiation required for functional tissue development. The objective of this study was fabrication of nanofibrous matrix from novel biodegradable poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol) (PPDO/PLLA-b-PEG) copolymer, and to examine cell proliferation, morphology of cell-matrix interaction with the electrospun nanofibrous matrix. The electrospun structure composed of PPDO/PLLA-b-PEG fibers with an average diameters of 380 nm, median pore size 8 microm, porosity more than 80% and mechanical strength 1.4 MPa, is favorable for cell-matrix interaction and supports the active biocompatibility of the structure. NIH 3T3 fibroblast cell seeded on the structure tend to maintain phenotypic shape and guided growth according to nanofiber orientation. Good capability of the nanofibrous structure for supporting the cell attachment and proliferation are observed. This novel biodegradable scaffold will be applicable for tissue engineering based upon its unique architecture, which acts to support and guide cell growth.     

Reactive oxygen species generation at the plasma membrane for antibody control

Generation of reactive oxygen species (ROS) at the plasma membrane can be a vehicle for oxidative unmasking or masking of auto antibodies in a tissue selective and controlled way. There are seven related NADPH oxidases (NOX 1-5, DuoNOX 1,2) which can be activated in various ways to produce superoxide and hydrogen peroxide at the plasma membrane. There is also a plasma membrane NADH oxidase which is under different control. ROS can also be produced by mitochondria or cytosolic oxidases under special conditions. The ROS generation provides oxidant for thiol oxidation or peroxynitrite formation which can be a basis for antibody modification. The specific controls of the oxidases in different tissues allow a basis for localized autoantibody modification in response to stress or environment.     

Behavior of synthetic polymers immobilized on a cell membrane

We used three kinds of polymers that interact with living cells in different modes: poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) and poly(vinyl alcohol) carrying alkyl side chains (PVA-alkyl), expected to anchor to the membrane lipid bilayer through hydrophobic interactions; N-hydroxysuccinimidyl-PEG (PEG-NHS), which covalently bonds with all kinds of membrane proteins having amino groups on cell surfaces; and polyelectrolytes, poly(ethylene imine) (PEI) and carboxylated PVA (PVA-COOH), which interact with cells electrostatically. CCRF-CEM (T-cell like) and HEK293 (adherent cell) cell lines were used. We followed the surface dynamics of fluorescently labeled polymers on living cells over time using confocal laser scanning microscopy and flow cytometry. PEI destroyed cells, while PVA-COOH did not interact with cells. PEG-lipid, PVA-alkyl, and PEG-NHS interacted with cells without cytotoxicity and existed on the cell surface even after cells were washed. PEG-lipid and PEG-NHS were rapidly excluded from the cell surface without cytoplasmic uptake, while PVA-alkyl assembled on the living cell surface was taken into the cytoplasm and then excluded. Most polymers were excluded within 24h although exclusion routes seemed to be different between polymers, suggesting that cell transplant surface modifications are shorter than has been assumed. The short life of modified polymers on the cell surface should be a consideration for cell transplant surface modifications.     

Optimum control of oxygen affinity of hemoglobin as an oxygen carrier solution for an artificial gill

An artificial gill was developed using a concentrated hemoglobin solution as an oxygen carrier solution, with the oxygen affinity controlled by temperature. Oxygen affinity of the concentrated hemoglobin solution was optimized for the artificial gill by adding inositol hexaphosphate as an allosteric effector and varying the pH and temperature. The oxyhemoglobin dissociation curve shifted to the right with increased ratios of inositol hexaphosphate to hemoglobin, decreased pH values, and higher temperatures. The optimum ratio of inositol hexaphosphate to hemoglobin was 5 : 1. Because lower pH promotes proton oxidation of hemoglobin, the optimum pH was 6.9. The oxyhemoglobin dissociation curve shifted to the right with higher temperatures. The amount of the shift in relation to temperature change was higher at higher temperatures. The oxygen transfer rate was markedly increased by changing the temperature of the oxygen carrier solution. The overall mass transfer coefficient decreased at higher oxygen partial pressures due to the gentle oxyhemoglobin dissociation curve. The flow rate of the oxygen carrier solution and heat transfer rate for heating of the oxygen carrier solution were markedly decreased by setting the range of temperature changes from 293 K to 310 K. The flow rate of the oxygen carrier solution required to supply 300 ml (STP)/min of oxygen was 21.7 l/min, and the heat transfer rate was 1165 kJ/min. Received: October 30, 2000 / Accepted: January 10, 2001     

High functional hollow fiber membrane modified with phospholipid polymers for a liver assist bioreactor

For practical application of a liver assist system with a tissue-conjugated hollow fiber membrane (HFM) bioreactor used in an extracorporeal therapy, it would require a highly sophisticated HFM which has both hemocompatibility on one side and cytocompatibility on the other side. In this study, we present a cellulose acetate (CA) HFM modified with 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers (PMB30 (MPC-co-n-butyl methacrylate) and PMA30 (MPC-co-methacrylic acid) for preparing a novel liver assist HFM bioreactor. A CA/PMB-PMA30 HFM modified asymmetrically on the inner and outer surface with the PMB30 and PMA30 was prepared successfully. Analysis with an X-ray photoelectron spectroscope showed that the intensity of the phosphorus atom attributed to the MPC units on the outer surface of the modified HFM was stronger than that of the inner surface. The PMA30 was immobilized on the outer surface of the CA/PMB30 blend HFM by a chemical condensation reaction. The CA/PMB-PMA30 HFM showed good water and solute permeability in comparison with the CA HFM. The morphologies of the adherent hepatocytes were round in shape in comparison with the cells that adhered on CA HFM. Furthermore, hepatocytes cultured on the inner surface of the CA/PMB-PMA30 HFM showed higher functional expression in terms of urea synthesis and albumin synthesis than that of the CA HFM.     

Singlet oxygen quenching by polyconjugated polymers derived from acenaphthene and acenaphthylene

Singlet oxygen quenching by polymers derived from acenaphthene and acenaphthylene is investigated by the oxidation of cis-1,4-polybutadiene with photochemically generated singlet oxygen. It is found that only the polymers with conjugated double bonds in the main chain, poly (1,2-acenaphthenediylidene) (1) and poly (1,2-acenaphthylenylene) (2) , are singlet oxygen quenchers. Poly(1,2-acenaphthenylene) (3) , with a saturated main chain, is no singlet oxygen quencher. Polymer 2 does not react with singlet oxygen. This is an indication that the quenching mechanism is a physical process.     

Hyperbaric oxygen as an adjunctive treatment for zygomycosis

Zygomycosis is a rare but emerging mycosis. Because of the sub-optimal efficacy of the standard antifungal treatment for this disease, hyperbaric oxygen (HBO) has been used occasionally as an adjunctive therapeutic modality. A review of 28 published cases of zygomycosis indicates that adjunctive HBO may be beneficial in diabetic patients (94% survival), whereas its benefit in the small group of patients with haematological malignancies or bone marrow transplants is doubtful (33% survival; p 0.02). Prolonged courses of HBO were associated with a higher survival (100% survival; p 0.003). Additional studies are required to assess the optimal timing and dose for HBO treatment.     

A new method for breath-to-breath determination of oxygen flux across the alveolar membrane

Summary A new method for breath-to-breath determination of the oxygen flux across the alveolar membrane is described. The principle of the method is to integrate the product of oxygen concentration and flow in the respiratory gas over an interval, which covers a complete respiratory cycle. The result is corrected for the change in oxygen content of the lungs through a formula, which, in contrast to those used in other methods, is independent of the residual capacity of the lungs.The method was evaluated with respect to repeatability by repetitive measurement of oxygen flux in twenty volunteer subjects, and with respect to accuracy by comparing the measured oxygen fluxes with those obtained by the gas collection method. The coefficient of variation was found to be 8% and the breath to breath determinations were, on an average, 6% lower than those of the gas collection method.