肝素化聚甲基硅氧烷-聚氧乙烯接枝物的合成及其体外抗凝血性能评价

以二甲基硅油接枝端羟基聚氧乙烯（ＰＤＭＳ ｇ ＰＥＯ ＯＨ）为基材，用二环己基碳二亚胺（ＤＣＣＩ）作脱剂，研究了羟基（ＯＨ）与肝素上的羧基（—ＣＯＯＨ）之间的脱水缩合反应，制备出肝素化的抗血栓材料ＰＤＭＳ ｇ ＰＥＯ Ｈｅｐ，并对其涂覆表面的肝素含量和体外抗凝血性能进行了初步评价．实验结果表明，肝素接枝的共聚物具有优良的抗凝血性能和一定的应用前景．     

Polymer bilayer formation due to specific interactions between beta-cyclodextrin and adamantane: a surface force study

The purposes of this study are to utilize the interactions between an adamantane end-capped poly(ethylene oxide) (PEO) and a cationic polymer of beta-cyclodextrin to build polymer bilayers on negatively charged surfaces, and to investigate the interactions between such layers. The association of this system in solution has been studied by rheology, light scattering, and fluorescence measurements. It was found that the adamantane-terminated PEO (PEO-Ad) mixed with the beta-cyclodextrin polymer gives complexes where the interpolymer links are formed by specific inclusion of the adamantane groups in the beta-cyclodextrin cavities. This results in a higher viscosity of the solution and growth of intermolecular clusters. The interactions between surfaces coated with a cationized beta-cyclodextrin polymer across a water solution containing PEO-Ad polymers were studied by employing the interferometric surface force apparatus (SFA). In the first step, the interaction between mica surfaces coated with the cationized beta-cyclodextrin polymer in pure water was investigated. It was found that the beta-cyclodextrin polymer adsorbs onto mica and almost neutralizes the surface charge. The adsorbed layers of the beta-cyclodextrin polymer are rather compact, with a layer thickness of about 60 A (30 A per surface). Upon separation, a very weak attractive force is observed. The beta-cyclodextrin solution was then diluted by pure water by a factor of 3000 and a PEO-Ad polymer was introduced into the solution. Two different architectures of the PEO-Ad polymer were investigated: a four-arm structure and a linear structure. After the adsorption of the PEO polymer onto the beta-cyclodextrin layer reached equilibrium, the forces were measured again. It was found that the weak repulsive long-range force had disappeared and an attractive force caused the surfaces to jump into contact, and that the compressed layer thickness had increased. The attractive force is interpreted as being due to a specific recognition between the hydrophobic adamantane groups on the PEO-Ad polymer and the hydrophobic cavity in the beta-cyclodextrin molecules. Furthermore, the attractive force observed on separation has increased significantly, which is a further indication of a specific interaction between the beta-cyclodextrin polymer and the adamantane groups.     

Surface properties of bottle-brush polyelectrolytes on mica: effects of side chain and charge densities

Surface properties of a series of cationic bottle-brush polyelectrolytes with 45-unit-long poly(ethylene oxide) side chains were investigated by phase modulated ellipsometry and surface force measurements. The evaluation of the adsorbed mass of polymer on mica by means of ellipsometry is complex due to the transparency of mica and its birefringence and low dielectric constant. We therefore employed a new method to overcome these difficulties. The charge and the poly(ethylene oxide) side chain density of the bottle-brush polymers were varied from zero charge density and one side chain per segment to one charge per segment and no side chains, thus spanning the realm from a neutral bottle-brush polymer, via a partly charged brush polyelectrolyte, to a linear fully charged polyelectrolyte. The adsorption properties depend crucially on the polymer architecture. A minimum charge density of the polymer is required to facilitate adsorption to the oppositely charged surface. The maximum adsorbed amount and the maximum side chain density at the surface are obtained for the polymer with 50% charged segments and the remaining 50% of the segments carrying poly(ethylene oxide) side chains. It is found that brushlike layers are formed when 25-50% of the segments carry poly(ethylene oxide) side chains. In this paper, we argue that the repulsion between the side chains results in an adsorbed layer that is non-homogeneous on the molecular level. As a result, not all side chains will contribute equally to the steric repulsion but some will be stretched along the surface rather than perpendicular to it. By comparison with linear polyelectrolytes, it will be shown that the presence of the side chains counteracts adsorption. This is due to the entropic penalty of confining the side chains to the surface region.     

Role of ion ligands in the attachment of poly(ethylene oxide) to a charged surface

Using a surface force balance we demonstrate unambiguously that high-molecular-weight poly(ethylene oxide) (PEO) does not adsorb onto mica from purified water with no added salt, a surprising observation in view of its strong adsorption on mica from aqueous 0.1 M KNO3 solution. Analysis of the force profiles, together with the known complexation of PEO with metal ions, suggests that the polymer attachment to the negatively charged surface is mediated by the hydrated potassium ion acting as a ligand.     

Reduction of protein adsorption to a solid surface by a coating composed of polymeric micelles with a glass-like core

Adsorption studies by optical reflectometry show that complex coacervate core micelles (C3Ms) composed of poly([4-(2-amino-ethylthio)-butylene] hydrochloride)(49)-block-poly(ethylene oxide)(212) and poly([4-(2-carboxy-ethylthio)-butylene] sodium salt)(47)-block-poly(ethylene oxide)(212) adsorb in equal amounts to both silica and cross-linked 1,2-polybutadiene (PB). The C3Ms have an almost glass-like core and atomic force microscopy of a dried layer of adsorbed C3Ms shows densely packed flattened spheres on silica, which very probably are adsorbed C3Ms. Experiments were performed with different types of surfaces, solvents, and proteins; bare silica and cross-linked 1,2-PB, NaNO(3) and phosphate buffer, and lysozyme, bovine serum albumin, beta-lactoglobulin, and fibrinogen. On the hydrophilic surface the coating reduces protein adsorption >90% in 0.1 M phosphate buffer, whereas the reduction on the coated hydrophobic surface is much lower. Reduction is better in phosphate buffer than in NaNO(3), except for the positively charged lysozyme, where the effect is reversed.     

Development of dextran-derivative arrays to identify physicochemical properties involved in biofouling from serum

To control protein adsorption on surfaces, low-fouling polymer coatings such as poly(ethylene oxide) (PEG or PEO) and polysaccharides are used. Their ability to resist protein adsorption is related to the layer structure, hence the immobilization mode. A polymer array technology was developed to study the structural diversity of carboxymethyl dextran (CMD) layers, whose immobilization conditions were varied. CMD arrays were analyzed by X-ray photoelectron spectroscopy (XPS) and by atomic force microscopy (AFM) colloidal probe force measurements. Serum protein adsorption was studied directly on the CMD arrays using surface plasmon resonance (SPR) microscopy. Physicochemical characterization revealed that pinning density regulates surface coverage and the amount of adsorbed molecules, and that salt concentration influences the surface structure of the charged polymer, forming extended or short layers. Protein adsorption experiments from serum showed that repulsive CMD layers are dense, with extended flexible chains. The present study underlines the usefulness of polymer arrays to study structural diversity of thin graft layers and to relate their physicochemical properties to their resistance to nonspecific protein adsorption.     

Effect of polymer architecture on the adsorption properties of a nonionic polymer

The adsorption of a linear- and bottle-brush poly(ethylene oxide (PEO))-based polymer, having comparable molecular weights, was studied by means of quartz crystal microbalance with dissipation monitoring ability (QCM-D) and AFM colloidal probe force measurements. The energy dissipation change monitored by QCM-D and the range of the steric forces obtained from force measurements demonstrated that linear PEO forms a more extended adsorption layer than the bottle-brush polymer, despite that the adsorbed mass is higher for the latter. Competitive adsorption studies revealed that linear PEO is readily displaced from the interface by the bottle-brush polymer. This was attributed to the higher surface affinity of the latter, which is governed by the number of contact points between the polymers and the interface, and the smaller loss of conformational entropy.     

Preparation of thin surface layers by grafting of PEO

We have developed a two‐stage process to graft poly(ethylene oxide) (PEO) onto a silica surface. In the first stage the adsorption of an anchor reactive polymer to the surface is carried out, and in the second stage the grafting of compatibilizing macromolecular tails is performed via the reactions of functional groups of the polymer anchored. Random copolymers of styrene and maleic anhydride (SM) were chosen as reactive anchoring polymers. The kinetics of adsorption of SM from dilute solutions onto the silica surface as well as the grafting of PEO to SM macromolecules adsorbed was experimentally investigated by null ellipsometry. A model of the structure at the surface is proposed.     

Use of cellulose derivatives on gold surfaces for reduced nonspecific adsorption of immunoglobulin G

This study addresses the design of protein-repellent gold surfaces using hydroxyethyl- and ethyl(hydroxyethyl) cellulose (HEC and EHEC) and hydrophobically modified analogues of these polymers (HM-HEC and HM-EHEC). Adsorption behavior of the protein immunoglobulin G (IgG) onto pure gold and gold surfaces coated with cellulose polymers was investigated and described by quartz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM) and contact angle measurements (CAM). Surfaces coated with the hydrophobically modified cellulose derivatives were found to significantly outperform a reference poly(ethylene glycol) (PEG) coating, which in turn prevented 90% of non-specific protein adsorption as compared to adsorption onto pure gold. HEC and EHEC prevented around 30% and 60% of the IgG adsorption observed on pure gold, while HM-HEC and HM-EHEC were both found to completely hinder biofouling when deposited on the gold substrates. Adsorption behavior of IgG has been discussed in terms of polymer surface coverage and roughness of the applied surfaces, together with hydrophobic interactions between protein and gold, and also polymer-protein interactions.     

Surfactant boundary lubricant film modified by an amphiphilic diblock copolymer

The effect of the uptake of a low-molecular-weight amphiphilic diblock copolymer on the morphology of didodecyldimethylammonium bromide (DDAB) adsorbed layers on mica, the interactions between two coated surfaces, and the frictional properties of the boundary film have been studied using an atomic force microscope and a dynamic surface forces apparatus nanotribometer. When DDAB-coated surfaces in aqueous solution were compressed, hemifusion or removal of the adsorbed surfactant bilayers could not be induced, and no frictional force could be measured between the surfaces, which display superior lateral cohesion and lubricant properties. Coadsorbing octadecyl end modified poly(ethylene oxide) chains at low density facilitates hemifusion, generating significant shear stress and leading to stick-slip instabilities. The mixed films regain their lateral cohesion at higher adsorbed copolymer densities, but an extra short-range attraction brings the adsorbed layers into adhesive contact without causing bilayer hemifusion. Here, noticeable frictional forces are also measured.     

On the stability of the polymer brushes formed by adsorption of ionomer complexes on hydrophilic and hydrophobic surfaces

We have studied the effect of normal forces and shear forces on the stability and functionality of a polymer brush layer formed upon adsorption of polymeric micelles on hydrophilic and hydrophobic surfaces. The micelles consist of oppositely charged polyelectrolyte blocks (poly(acrylic acid) and poly(N-methyl 2-vinyl pyridinium iodide), and a neutral block (poly(vinyl alcohol)) or neutral grafts (poly(ethylene oxide)). The strength of the attachment of the micellar layers to various substrates was evaluated with Atomic Force Microscopy. Flow cell experiments allowed for the evaluation of long-term stability of coatings in lateral flow. Fixed angle optical reflectometry was used to quantify protein (BSA) adsorption on the micellar layers after their exposure to flow. The results show that adsorbed micellar layers are relatively weakly attached to hydrophobic surfaces and much stronger to hydrophilic surfaces, which has a significant impact on their stability. Adsorbed layers maintain their ability to suppress protein adsorption on hydrophilic surfaces but not on hydrophobic surfaces. Due to the relatively weak attachment to hydrophobic surfaces the structure of adsorbed layers may easily be disrupted by lateral forces, such that the complex coacervate-brush structure no longer exists.     

Selective adsorption of poly(ethylene oxide) onto a charged surface mediated by alkali metal ions

Using a surface force balance, we have measured normal and shear interactions between mica surfaces across pure water and across 0.1 M aqueous solutions of LiNO3, NaNO3, KNO3, and CsNO3, both prior to adding polymer and following addition of 1.5 x 10(-4) w/w poly(ethylene oxide) (PEO, Mw = 170 kD) and overnight incubation. Our results reveal that while the PEO adsorbs strongly from the KNO3 and CsNO3 solutions, unexpectedly it does not adsorb at all from the LiNO3 and NaNO3 salt solutions. We attribute this to the different nature of the hydration layers about the alkali metal ions: these favor liganding to the negatively charged mica surface of the etheric -O- group on the ethylene oxide monomer for the case of the more weakly hydrated K+ and Cs+, but not for the case of Na+ or Li+ with their more strongly bound water. A simple model relating the electrostatic energy changes occurring upon such liganding to the experimentally measured hydration energies of the different alkali metal ions supports this attribution.     

A physico-chemical investigation of poly(ethylene oxide)-block-poly(L-lysine) copolymer adsorption onto silica nanoparticles

The adsorption behavior of poly(ethylene oxide)-b-poly(L-lysine) (PEO(113)-b-PLL(10)) copolymer onto silica nanoparticles was investigated in phosphate buffer at pH 7.4 by means of dynamic light scattering, zeta potential, adsorption isotherms and microcalorimetry measurements. Both blocks have an affinity for the silica surface through hydrogen bonding (PEO and PLL) or electrostatic interactions (PLL). Competitive adsorption experiments from a mixture of PEO and PLL homopolymers evidenced greater interactions of PLL with silica while displacement experiments even revealed that free PLL chains could desorb PEO chains from the particle surface. This allowed us to better understand the adsorption mechanism of PEO-b-PLL copolymer at the silica surface. At low surface coverage, both blocks adsorbed in flat conformation leading to the flocculation of the particles as neither steric nor electrostatic forces could take place at the silica surface. The addition of a large excess of copolymer favoured the dispersion of flocs according to a presumed mechanism where PLL blocks of incoming copolymer chains preferentially adsorbed to the surface by displacing already adsorbed PEO blocks. The gradual addition of silica particles to an excess of PEO-b-PLL copolymer solution was the preferred method for particle coating as it favoured equilibrium conditions where the copolymer formed an anchor-buoy (PLL-PEO) structure with stabilizing properties at the silica-water interface.     

Dynamic light scattering studies of poly(ethylene oxide) adsorbed on Laponite: layer conformation and its effect on particle stability

Dynamic light scattering has been used to determine the hydrodynamic thickness of poly(ethylene oxide) (PEO) adsorbed on synthetic anisotropic clay particles (Laponite) as a function of molecular weight. The layer thicknesses, and their increase with molecular weight, indicate that the conformation of the adsorbed layer is very compact and is much smaller than those normally observed for polymer adsorption on flat interfaces. The aggregation kinetics of the polymer coated particles in 5 mM NaCl was analyzed in a quantitative manner, revealing that the potential barrier to aggregation is strongly enhanced when polymer is present.     

Protein resistance of (ethylene oxide)n monolayers at the air/water interface: effects of packing density and chain length

Protein adsorption on poly(ethylene oxide) (PEO) and oligo(ethylene oxide) (OEO) monolayers is studied at different packing densities using the Langmuir technique. In the case of a PEO monolayer, a protein adsorption minimum is revealed at sigma(-1) = 10 nm(2) for both lysozyme and fibrinogen. Manifested are two packing density regimes of steric repulsion and compressive attraction between PEO and a protein on top of the overall attraction of the protein to the air/water interface. The observed protein adsorption minimum coincides with the maximum of the surface segment density at sigma(-1) = 10 nm(2). However, OEO monolayer presents a different scenario, namely that the amount of protein adsorbed decreases monotonically with increasing packing density, indicating that the OEO chains merely act as a steric barrier to protein adsorption onto the air/water interface. Besides, in the adsorption of fibrinogen, three distinct kinetic regimes controlled by diffusion, penetration and rearrangement are recognized, whereas only the latter two were made out in the adsorption of lysozyme.     

Hydrogel networks of poly(ethylene oxide) star-molecules supported by expanded polytetrafluoroethylene membranes: characterization, biocompatibility evaluation and glucose diffusion characteristics

The present work discusses the grafting by electron beam irradiation of poly(ethylene oxide) (PEO) star-shaped polymers onto porous expanded polytetrafluoroethylene (EXPTFE) surfaces. The resulting materials are intended to combine the good biocompatible properties of PEO with the outstanding mechanical properties of PTFE. The star-shaped PEOs were synthesized via anionic polymerization. 3 Mev electron beam irradiation was applied to graft these PEO stars onto porous EXPTFE surfaces. The hydrophobic EXPTFE surface had to be pre-modified with N-vinylpyrrolidone. ESCA was used to quantify the amount of grafted star-shaped PEO. Unmodified EXPTFE surfaces are well known, when implanted in a body, to be rapidly covered by a layer of cells and fibrin. The EXPTFE coated with PEO were implanted in the peritoneal cavity of rats (or under the back skin). This implantation did not induce any inflammation reactions and SEM analysis had attested the absence of adsorbed cells and fibrin. The glucose diffusion properties of these membranes were studied by a lag time analysis method and compared to those of pure PEO hydrogels. As expected, glucose diffuses through the hydrogel coated membrane and diffusion is not affected by the presence of the EXPTFE membrane.     

Characterization of low-fouling ethylene glycol containing plasma polymer films

Low-protein-fouling poly(ethylene glycol) (PEG-like) plasma polymer films were prepared using radio frequency glow discharge polymerization of diethylene glycol dimethyl ether (DGpp) on top of a heptylamine plasma polymer primer layer. By varying the plasma deposition conditions, the chemistry of the DGpp film was influenced, especially in regard to the level of ether content, which in turn influenced the relative levels of bovine serum albumin and lysozyme protein fouling. Surface potential measurements indicated that these surfaces carried a net negative charge. While protein fouling remained low ( approximately 10 ng/cm2), there was a slightly higher level of the positively charged protein adsorbed on these films than the negative protein. The interaction forces measured between a silica spherical surface on both "high"- and "low"-protein-fouling DGpp films were all repulsive and short ranged (2-3 nm). There was no correlation between the surface forces measured for high- and low-protein-fouling DGpp films. Thus, it appears that enthalpic effects are very important in reducing protein adsorption. We therefore conclude that it is the concentration of residual, ethylene glycol containing species that are the crucial parameter determining protein resistance due to a combination of both entropic and enthalpic effects.     

Compact poly(ethylene oxide) structures adsorbed at the ethylammonium nitrate-silica interface

The adsorption of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) onto silica from ethylammonium nitrate (a protic ionic liquid) has been investigated using colloid probe AFM force curve measurements. Steric repulsive forces were measured for PEO, confirming that PEO can compete with the ethylammonium cation and adsorb onto silica. The range of the repulsion increases with polymer molecular weight (e.g., from 1.4 nm for 0.01 wt % 10 kDa PEO to 40 nm for 0.01 wt % 300 kDa PEO) and with concentration (e.g., from 16 nm at 0.001 wt % to 78 nm at 0.4 wt % for 300 kDa PEO). Fits to the force curve data could not be obtained using standard models for a polymer brush, but excellent fits were obtained using the mushroom model, suggesting the adsorbed polymer films are compressed and relatively poorly solvated. No evidence for adsorption of 3.5 kDa PPO could be detected up to its solubility limit.     

Small-angle neutron scattering study of adsorbed pluronic tri-block copolymers on laponite

The adsorption of selected poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymers on synthetic clay particles (laponite) has been investigated. The adsorbed amount and distribution of polymer was determined as a function of relative block composition and size, using the technique of contrast variation small-angle neutron scattering. The pluronic molecules appear to adsorb via a preferential segregation of hydrophobic PPO segments at the surface, with hydrophilic PEO segments dangling into solution. The effect of the PPO segments is substantial with large increases in adsorbed amount and layer thickness as the anchor fraction decreases/PEO chain length increases. This is in direct contrast to the behavior observed for PEO homopolymer adsorption (of much higher molecular weights) where the adsorbed amount and layer thickness are smaller and change little with molecular weight.     

Synthesis and interfacial properties of novel cationic polyelectrolytes with brush-on-brush structure of poly(ethylene oxide) side chains

Novel cationic polyelectrolytes with a brush-on-brush structure of poly(ethylene oxide) (PEO) side chains and a charge-containing polyacrylate backbone were synthesized. The PEO side chains were not directly attached to the backbone but via polymethacrylate spacers, thus locating the PEO chains a distance away from the charged units of the backbone. The cationic brush-on-brush polyelectrolytes with high density of PEO chains showed a strong affinity to silica surfaces, provided the backbone charge density was high enough. The adsorption of these polymers was studied by QCM-D giving very high sensed mass, 20 mg/m². It was shown by direct force measurements that protective surface layers were formed by the novel polyelectrolytes, generating strongly repulsive steric forces, which provided an effective barrier against flocculation. The adsorbed layer was sufficiently robust to withstand sliding experiments under a pressure of up to 35 MPa. The friction force in water was very low, and the lubrication was characterized by a friction coefficient in the range of 0.02-0.06.