MMA/MPEOMA copolymers as coating materials for improved blood compatibility: protein adsorption study

Surface-induced thrombosis remains one of the main problems in the development of blood-contacting devices. When a foreign surface comes in contact with blood, the initial blood response is adsorption of blood proteins, followed by platelet adhesion and activation, leading to thrombus formation. A particularly effective polymer for the prevention of protein adsorption and platelet adhesion appears to be polyethylene oxide (PEO). In this study, water-insoluble copolymers of methyl methacrylate (MMA) and methoxy PEO monomethacrylates (MPEOMA) with different PEO molecular weights (200, 400, and 1000) and monomer composition were synthesized and characterized by gel permeation chromatography and ¹H-nuclear magnetic resonance spectroscopy. The synthesized copolymers were coated on glass slides by a spin coating method to prepare PEO-rich surfaces as blood-compatible surfaces. The surface properties of the copolymers and their interaction with blood proteins (albumin, γ-globulin, fibrinogen, and plasma proteins) were investigated by the measurement of water contact angles and by electron spectroscopy for chemical analysis, respectively. It was observed that the protein adsorption on the copolymer surfaces decreased with increasing PEO molecular weight and MPEOMA content in the copolymers. The copolymers with long PEO chains in MPEOMA (MMA/MPEO₀₀₀MA copolymers) were effective in preventing protein adsorption, even though their MPEOMA content was less than the copolymers with shorter PEO chains. © 1999 Kluwer Academic Publishers     

Layer‐by‐Layer Fabrication of Covalently Crosslinked and Reactive Polymer Multilayers Using Azlactone‐Functionalized Copolymers: A Platform for the Design of Functional Biointerfaces

We report a method for modulating the physicochemical properties of surfaces that is based on the reactive layer‐by‐layer fabrication of covalently crosslinked thin films using azlactone‐functionalized copolymers. We demonstrate that copolymers containing different molar ratios of methyl methacrylate (MMA) and 2‐vinyl‐4,4‐dimethylazlactone (VDMA) can be alternately deposited with poly(ethyleneimine) to assemble covalently crosslinked thin films. Characterization using ellipsometry demonstrates that, in general, film growth and thickness decrease as the content of reactive, azlactone functionality in the copolymer used to assemble the film decreases. Reflective infrared spectroscopy experiments demonstrate that films fabricated from MMA:VDMA copolymers contain residual azlactone functionality and that these reactive groups can be exploited to modify film‐coated surfaces. Fabricating films from MMA:VDMA copolymers containing different compositions permitted modulation of the density of reactive groups within the films and, thus, the extent to which the films are functionalized by exposure to small molecule amines. For example, functionalization of MMA:VDMA copolymer films with the small molecule D ‐glucamine resulted in films with water contact angles that varied with the composition of the copolymer used to fabricate the film (e.g., as the azlactone content in the film increased, glucamine‐modified films became more hydrophilic). We demonstrate further that treatment of copolymer‐containing films with glucamine resulted in changes in the numbers of mammalian cells that grow on the surfaces of the films. Our results suggest the basis of methods that could be used to modulate or tune the density of chemical and biological functionality presented on surfaces of interest in a variety of fundamental and applied contexts.     

Heparin-containing block copolymers

Newly synthesized heparin-containing block copolymers, consisting of a hydrophobic block of polystyrene (PS), a hydrophilic spacer-block of poly (ethylene oxide) (PEO) and covalently bonded heparin (Hep) as bioactive block, were coated either onto glass, poly (dimethylsiloxane), polyurethane or PS substrates. Coated surfaces were characterized by determination of the surface-bound heparin activity, adsorption of AT III, plasma recalcification time assays, adhesion of platelets and by an ex vivo rabbit A-A shunt model.It was demonstrated that heparin was available at the surface of all heparin-bound surfaces to interact with AT III and thrombin and to prevent the formation of clots. The maximum immobilized heparin activity was found to be 5.5×10^-3 U cm^-2. Coated surfaces showed a significant prolongation of the plasma reclacification times as compared to control surfaces, due to surface-immobilized heparin. The platelet adhesion demonstrated that platelets reacted only minimally with the heparin-containing block copolymers in the test system and that the heparin-containing block copolymers seemed to passify the surface as compared to control surfaces. In the ex vivo A-A shunt experiments, which were carried out under low flow and low shear conditions, the heparin-containing block copolymers exhibited prolonged occlusion times, indicating the ability of the heparin-containing block copolymers to reduce thrombus formation at the surface.     

MA/ATMP共聚物的微观结构及其热稳定性研究

采用不同配比的反应型受阻胺4-丙烯酰氧基-2,2,6,6-四甲基哌啶醇酯(ATMP)与丙烯酸甲酯(MA)进行溶液光引发共聚合.用核磁共振对共聚物的组成及其序列分布进行了表征.在此基础上,对不同微观结构的共聚物进行了热稳定性及玻璃化温度的测定,确定了共聚物中各基团的断裂分解温度、材料的玻璃化转变,以及这些变化与共聚物链组成和序列分布的关系.     

Heparin-containing block copolymers

Newly synthesized heparin-containing block copolymers, consisting of a hydrophobic block of polystyrene (PS), a hydrophilic spacer-block of poly(ethylene oxide) (PEO) and covalently bound heparin (Hep) as bioactive block, were coated on aluminium, glass, polydimethylsiloxane (PDMS), PS or Biomer substrates. Surfaces of coated materials were characterized by transmission electron microscopy (TEM), contact angle measurements and X-ray photoelectron spectroscopy for chemical analysis (XPS). It was demonstrated by TEM that thin films of PS-PEO and PS-PEO-Hep block copolymers consisted of heterogeneous microphase separated structures. Using sessile-drop and Wilhelmy plate dynamic contact angle measurements, insight was provided into the hydrophilicity of the surfaces of the coatings. Measurements with hydrated coatings of PS-PEO and PS-PEO-Hep block copolymers revealed that the surfaces became more hydrophilic during immersion in water, due to relaxation/reorientation, or swelling of PEO or PEO-Hep domains, respectively. XPS results for PS, PEO, heparin and PS-PEO as powder agreed well with qualitative and quantitative predictions. XPS results for films of PS-PEO and PS-PEO-Hep block copolymers showed enrichments of PEO in the top layers of the coatings. This effect was more pronounced for hydrated surfaces. Only small amounts of heparin were detected at the surface of coatings of PS-PEO-Hep block copolymers.     

高稳自组装PEG-PMMA-HDMA载药胶团的制备及其性能研究

以PEG2000-Br为引发剂,甲基丙烯酸甲酯(MMA)为单体,1,6-己二醇二甲基丙烯酸酯(HDMA)为交联剂,采用原子转移自由基聚合( ATRP)制备了两亲交联聚合物PEG-PMMA-HDMA以及作为对照样的线性聚合物PEG-PMMA.由GPC、1 H-NMR研究可知,PEG-PMMA为线性分子,而PEG-PMMA...     

新型硅丙透明疏水膜的制备及性能

以硅烷偶联剂KH 560和以溶液法制得的含羟基的丙烯酸树脂为原料,通过硅氧基与羟基的水解缩聚反应,制备了透明的有机硅疏水膜。用FT-IR、GPC、固含量的测试以及接触角测定,对合成产物结构和亲/疏水特性进行分析表征,并讨论了KH 560的添加对疏水膜耐水性和耐热性的影响。     

Dispersion and stability of nanoparticles in electrophoretic displays

This work is focused on investigating the influence of morphologies and composition of polymer coating layers on the dispersion stability of the hybrid particles dispersed in non-aqueous solvent for use in electrophoretic displays. Black copper chromite/polymer core-shell nanoparticles are synthesized through radical grafting polymerization. A series of methylacrylate monomers containing a plurality of alkyl side chains with different length, methyl methacrylate (MMA), tert-butylmethacrylate (TBMA), 2-ethylhexyl methacrylate (EHMA) and lauryl methacrylate (LMA), are employed for polymer encapsulation. The morphologies and composition of Black 1G/polymer core-shell nanoparticles are characterized by a combination of TEM and FTIR measurements. The UV–vis transmittance results demonstrate that the longer or more branching the monomers used in polymer modification, the more stable the particle suspension. For homopolymer encapsulation, monomer with an alkyl chain containing more than about four carbon atoms will impart good dispersibility to particles. Moreover, incorporation of a second monomer into polymer backbone can adjust the dispersion stability of particle suspension. When 15 mol% of MMA or 5 mol% of TBMA is added into PLMA backbone, the particles will gain better dispersibility than particles coated with 100 mol% LMA. If EHMA acts as main monomer, addition of a second monomer will decrease the dispersibility instead. These findings may be a guideline to tune electrophoretic medium stability and improve life of EPDs. Within this study, A dual-particle electrophoretic dispersion of P (4-VP-co-LMA) anchored Black 1G particles and white TiO₂ was prepared to show black/white image under a bias voltage of 5 V.     

Hydrolytic degradation of PCL/PEO copolymers in alkaline media

PCL/PEO copolymers with different compositions were obtained from ring opening polymerization of -caprolactone in the presence of ethylene oxide and characterized by various analytical techniques. Data collected from DSC and X-ray diffractometry suggested that the copolymer chains possess a blocky structure, leading to both PCL and PEO-type crystalline structures. Hydrolytic degradation of these copolymers was carried out in a pH=10.6 carbonate buffer solution at 37 °C. Comparison was made with a PCL homopolymer and a PCL/PEG blend which had the same gross composition as one of the copolymers. The results showed that the presence of PEO sequences considerably enhanced the hydrophilicity of the copolymers as compared with PCL homopolymer. Nevertheless, the degradability of PCL chains was not enhanced due to the phase separation between the two components. These materials should be of great interest for biomedical uses such as matrices for sustained drug delivery because of the presence of both hydrophilic and hydrophobic microdomains. ©2000 Kluwer Academic Publishers     

Quantitative analysis and structure determination of styrene/methyl methacrylate copolymers by pyrolysis gas chromatography

A pyrolysis gas chromatography (Py-GC) method has been developed to study the composition and microstructure of styrene/methyl methacrylate (STY/MMA) copolymers. The composition was quantified by Py-GC using monomer peak intensity. Because of the poor stability of methyl methacrylate oligomers, neither MMA dimer nor MMA trimers were detected under normal pyrolysis conditions. The number-average sequence length for STY was determined by pure and hybrid trimer peak intensities. The number-average sequence length for MMA was determined by using formulas that incorporate composition and the number-average sequence length of STY. This method is a new approach for the investigation of the microstructure of those copolymers that do not produce dimer and trimer peaks upon pyrolysis.     

Synthesis of densely grafted copolymers with tert-butyl methacrylate/2-(dimethylamino ethyl) methacrylate side chains as precursors for brush polyelectrolytes and polyampholytes

Methacrylate-based densely grafted copolymers were synthesized by atom transfer radical polymerization (ATRP) and activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP) techniques. The linear poly(2-(2-bromoisobutyryloxy)ethyl methacrylate) PBIEM prepared by ATRP served as a macroinitiator backbone. The “grafting from” strategy was used to initiate polymerization of tert-butyl methacrylate (tBuMA) from PBIEM under ATRP and/or AGET ATRP conditions yielding densely grafted copolymers PBIEM-graft-P(tBuMA). The low polydispersity indices (PDI) of the synthesized brushes evidenced by SEC analysis were consistent with a controlled/living radical polymerization (CLRP) mechanism. The chlorine-terminated PBIEM-graft-P(tBuMA)-Cl macroinitiators were subsequently employed for chain extension with 2-(dimethylamino ethyl) methacrylate (DMAEMA) yielding densely grafted copolymers with diblock copolymer side chains PBIEM-graft-P(tBuMA)-block-PDMAEMA. Further, PBIEM macroinitiator was used to initiate the copolymerization of a binary mixture of tBuMA and DMAEMA through both ATRP and AGET ATRP initiating systems, yielding densely grafted copolymers with statistical distribution of the side chains. The reactivity ratios for random graft copolymerization of tBuMA and DMAEMA from PBIEM backbone established by three different methods (Finemann-Ross, Kelen-Tüdös and Error-in-Variable) did not substantially differ from literature values for conventional free-radical copolymerization of the same monomers. Polyampholyte brushes with PMAA-stat-PDMAEMA side chains were eventually synthesized by hydrolysis of the shielding tert-butyl groups.     

Nanoscale characterization of carbazole-indole copolymers modified carbon fiber surfaces

Polycarbazole, carbazole and indole containing copolymers were electrochemically coated onto carbon fiber. The resulting polymers and copolymers were characterized by scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. Characterization of the thin polymer films were performed on the polymer-coated surface of the carbon fiber. Therefore, the results obtained could elucidate the relationship between the initial feed monomer ratio, the resulting polymer/copolymer film morphology and the surface structure formed. The thickness increase (in diameter) was 0.3 and 0.9 microm, for two different composition of carbazole/indole on the carbon fiber. The carbon fibers coated with copolymer thin films were from 6.5 to 8.2 microm in diameter (from AFM measurement).     

Intact endothelial cell sheet harvesting from thermoresponsive surfaces coated with cell adhesion promoters.

Recently, with the development of smart polymers, research has looked to using thermoresponsive polymers as cell culture substrates. These novel surfaces allow the cultivation of cells without enzymes using the thermoresponsive phase transition property of poly(N-isopropylacrylamide) (PNIPAAm). However, this requires expensive techniques to generate a sufficiently thin film that allows cell adhesion. In this study, we looked at simple solvent cast films which normally show poor cell adhesion, but here the films are coated with cell adhesion promoters (CAPs) to improve cell growth without altering the copolymer thermoresponsive behaviour.A copolymer of PNIPAAm and N-tert-butylacrylamide (NtBAm) with a ratio of 85:15, respectively, was synthesized and solvent cast. The copolymer films were coated with CAPs, such as collagen, fibronectin and laminin, to increase their cell adhesion and growth properties. Cell activity measured by the alamarBlue assay showed similar results for coated copolymer films and standard tissue culture plastic controls. Deposition of CAPs on to the copolymer films was characterized by scanning electron microscopy and atomic force microscopy. Cell detachment from the copolymer films is not affected by the surface coatings of CAPs, and endothelial cells are recovered as an intact sheet, which has great potential for uses in tissue engineering applications. The results demonstrate a versatile method for the cultivation of cells while eliminating the need for the use of digestive enzymes such as trypsin. This study shows that cultivation on physically bonded PNIPAAm copolymers is viable and achievable by relatively simple methods.     

Behaviors of keratinocytes and fibroblasts on films of PLA50–PEO–PLA50 triblock copolymers with various PLA segment lengths

The growth of human primary keratinocytes and fibroblasts on PLA–PEO–PLA copolymer films was investigated as an intermediate stage of a strategy aimed at making implantable dermo-epidermal substitutes. Four PLA–PEO–PLA triblock copolymers with the same PEO block and different dl-lactic acid/ethylene oxide molar ratios (LA/EO) (0.8, 1.4, 1.8 and 2), were synthesized and characterized by ¹H-nuclear magnetic resonance and infrared spectroscopy. The films made of these copolymers were more hydrophilic than PLA₅₀ and than tissue culture polystyrene controls according to contact angles with water. Proliferation and adhesion of human skin cells were evaluated by MTT assay and by scanning electron microscopy. The presence of PEO in the triblock copolymers influenced cell adhesion and proliferation of fibroblasts, whereas keratinocyte adhesion and proliferation were not affected. These features emphasize the interest of PLA–PEO–PLA triblock copolymers to serve as better compounds than the racemic PLA previously investigated to make supports for human skin primary cells and scaffolds for skin engineering.     

Release of Ciprofloxacin from Chondroitin 6-Sulfate-Graft-Poloxamer Hydrogel In Vitro for Ophthalmic Drug Delivery

The system was designed to use Poloxamer as a vehicle for ophthalmic drug delivery using in situ gel formation property. To enhance the wound healing and cell adhesion as well as transparency of Poloxamer hydrogel, chondroitin 6-sulfate (C6S) was introduced into Poloxamer. For this purpose, mono amine-terminated Poloxamer (MATP), which was end-capped with ethylene amine group only in one side of terminal hydroxyl groups of Poloxamer, was synthesized. Subsequently, C6S-graft-Poloxamer copolymer (C6S-g-Poloxamer) was prepared by reaction between the amine groups of MATP and carboxyl groups of C6S in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carboimide (EDC). The coupling of MATP with C6S was clarified by ¹H-NMR and FT-IR spectroscopy. The gelation temperature of graft copolymers was determined by measuring the temperature at which immobility of the meniscus in each solution was first noted. Release behavior of ciprofloxacin from C6S-g-Poloxamer hydrogel in vitro was investigated as a function of C6S content in the graft copolymer by a spectrophotometric assay at 287 nm using an UV spectrophotometer. Differences in the adhesion and morphology of human lens cell between Poloxamer- and C6S-g-Poloxamer-coated surfaces were also investigated. The gelation temperatures of C6S-g-Poloxamer copolymers were lowered with increasing of the concentration of the copolymer and decreasing of C6S content. The release of ciprofloxacin from the graft copolymer was sustained compared with Poloxamer itself and decreased with increasing the content of C6S in the copolymer due to the in situ gel formation of the copolymer and viscous properties of C6S. Human lens cells (B3) adhered to C6S-g-Poloxamer-coated surface were observed as transformed shapes after 2 days. The bioadhesive and thermally gelling of these graft copolymers will be expected to be an excellent drug carrier for the prolonged delivery to surface of the eye.     

苯基喹啉/丙烯酸酯共聚物的合成及荧光性能研究

合成了一种新型的喹啉衍生物单体-2-苯基喹啉-4-羧酸-丙烯酸-乙二醇二酯(PQFAED),并通过乳液聚合的方法制备了PQFAED和丙烯酸酯单体(MMA/MAA/BA)的共聚物-P(PQFAED/MMA/MAA/BA)。用IR、UV、GPC、TGA、PGC-MS及荧光光谱表征了单体及共聚物的结构,分析了硝基爆炸物(TNT、RDX及PETN)对该共聚物膜的荧光猝灭作用。结果表明,共聚物薄膜的最大发射波长为436nm,相对于单体的最大发射峰发生了36nm的红移;荧光"结构自猝灭效应",使PQFAED在相同生色团浓度下的荧光强度远低于其相应共聚物的荧光强度;共聚物薄膜对多硝基爆炸物有较好的荧光响应,可作为爆炸物检测的传感材料。     

9,9-二(丙酸二甲氨基乙酯)芴共聚物的合成及荧光性能

采用迈克尔加成反应制备了单体2,7-二溴-9,9-二(丙酸二甲氨基乙酯)芴(FDMAEA);采用Suzuki偶合反应制备了不同FDMAEA结构单元含量的醇溶性9,9-二(丙酸二甲氨基乙酯)芴-9,9-二辛基芴共聚物(PFDMAEA)。通过核磁共振、凝胶渗透色谱、溶解性测试、紫外-可见光光谱、荧光发射光谱等对其进行了分析研究。结果表明,成功合成了2,7-二溴-9,9-二(丙酸二甲氨基乙酯)芴及9,9-二(丙酸二甲氨基乙酯)芴-9,9-二辛基芴共聚物。该共聚物在极性溶剂,如甲醇中具有良好的溶解性。由于含有DMAEA支链的PFDMAEA主链容易扭曲,共轭长度变短,共聚物的紫外吸收光谱和荧光光谱随着FDMAEA含量的增加而发生蓝移。荧光发光光谱研究表明,溶剂的极性、溶液的浓度、温度和pH值对共聚物的发光性能有很大的影响。随着溶剂极性增大,共聚物的荧光发射强度不断增加。荧光发射强度随溶液浓度的增加先增加后降低,随着溶液温度的上升而降低。当溶液pH值由1增大到14时,荧光强度不断降低,直至淬灭。     

Polystyrene/wood composites and hydrophobic wood coatings from water-based hydrophilic-hydrophobic block copolymers

 The combination of synthetic thermoplastic polymers and wood is normally problematic because wood surfaces are hydrophilic while typical thermoplastic polymers are hydrophobic. A possible solution is to use block copolymer coupling agents. In this work we show the use of a potentially useful synthetic method of producing hydrophilic-hydrophobic block copolymers as hydrophobic coatings and coupling agents in polystyrene/wood flour composites. In particular, wood veneers are coated with water-based emulsions of hydrophilic-hydrophobic block copolymers from styrene and methacrylic acid. Dried coated surfaces are shown to become hydrophobic through dynamic contact angle measurements. When wood flour is coated with the hydrophilic-hydrophobic block copolymer based on styrene and acrylic acid, significant improvement in the ultimate tensile properties of composites formed from coated wood flour/polystyrene mixtures is realized. Since no volatile organic compounds (VOCs) are used in coating wood surfaces and subsequent composite production, improvement in mechanical properties of thermoplastic/wood flour composites are shown to occur in environmentally responsible formulations. Received: 13 May 1999 / Accepted: 5 February 2000     

Adhesion and growth of vascular smooth muscle cells in cultures on bioactive RGD peptide-carrying polylactides

The surface of poly(l-lactide) (PLLA) films deposited on glass coverslips was modified with poly(dl-lactide) (PDLLA), or 1:4 mixtures of PDLLA and PDLLA-b-PEO block copolymers, in which either none, 5% or 20% of the copolymer molecules carried a synthetic extracellular matrix-derived ligand for integrin adhesion receptors, the GRGDSG oligopeptide, attached to the end of the PEO chain. The materials, perspective for vascular tissue engineering, were seeded with rat aortic smooth muscle cells (11,000 cells/cm²) and the adhesion, spreading, DNA synthesis and proliferation of these cells was followed on inert and bioactive surfaces. In 24-h-old cultures in serum-supplemented media, the number of cells adhering to the PDLLA-b-PEO copolymer was almost eight times lower than that on the control PDLLA surface. On the surfaces containing 5% and 20% GRGDSG-PEO-b-PDLLA copolymer, the number of cells increased 6- and 3-fold respectively, compared to the PDLLA-b-PEO copolymer alone. On PDLLA-b-PEO copolymer alone, the cells were typically round and non-spread, whereas on GRGDSG-modified surfaces the cell spreading areas approached those found on PDLLA, reaching values of 991 μm² and 611 μm² for 5% and 20% GRGDSG respectively, compared to 958 μm² for PDLLA. The cells on GRGDSG-grafted copolymers were able to form vinculin-containing focal adhesion plaques, to synthesize DNA and even proliferate in a serum-free medium, which indicates specific binding to the GRGDSG sequences through their adhesion receptors.     

N-异丙基丙烯酰胺共聚物的温敏性

采用自由基水溶液聚合方法制备出了N-异丙基丙烯酰胺(N IPA)温敏共聚物P(AM-N IPA);首次在P(AM-N IPA)结构中引入丙烯酸钠(N aAA)单体结构单元,合成了离子型共聚物P(AM-N IPA-N aAA);考察了共聚物P(AM-N IPA)和P(AM-N IPA-N aAA)溶液温敏性的影响因素;分别采用荧光光谱分析法以及乌氏黏度计稀释法对共聚物溶液温敏机理进行了研究。结果表明,不同共聚单体的配比以及单体含量对共聚物溶液低临界溶解温度(LCST)均有显著影响;当温度高于共聚物低临界溶解温度时,共聚物分子链上的疏水基团的缔合作用增强,导致疏水聚集结构的形成,聚合物分子链发生去溶剂化作用,在共聚物稀溶液中表现为线团收缩,在共聚物亚浓溶液中表现为共聚物分子间聚集发生相分离。