涤纶材料表面固定水蛭素及其血液相容性研究

利用紫外辐照仪在聚对苯二甲酸乙二醇酯(涤纶,PET)膜表面接枝聚丙烯酸(PET-AA)长链分子,再通过化学方法进一步固定水蛭素,获得的改性表面的X光电子能谱分析表明水蛭素分子被有效地固定在PET表面.改性表面的水接触角降低,亲水性得到改善.体外血小板粘附实验的结果显示,固定了水蛭素的PET薄膜的血液相容性比未改性的PET膜有明显的改善.     

In vitro investigation of the effect of plasticizers on the blood compatibility of medical grade plasticized poly (vinyl chloride)

This paper reports the results of an in vitro investigation into the blood response of medical grade poly (vinyl chloride) (PVC), and two types of plasticized PVC in tubing or sheet form, with di-(2-ethylhexyl)phthalate (DEHP) and di(isononyl) cyclohexane-1,2-dicarboxylate (HEXAMOLL^® DINCH) as plasticizer, were selected for assessment of complement activation, coagulation system and platelet activation. The results of the study show that not only the plasticizers at PVC surface have an influence on complement activation, but also the incubation condition such as incubation time and the diameter of PVC tubing. Under static status, C3a, C5a and SC5b-9 concentration in the blood were higher after contacting with PVC plasticized with DEHP (PVC1) than after contacting with PVC plasticized with DINCH (PVC2). However, under dynamic circulation, the results were totally converse, which may be due to smaller diameter and higher shear rate of PVC2. In addition, there was a significant increase of activated partial thrombin time (APTT) and decrease of FIX concentration after plasma contacting with the PVC tubing, which indicated that the intrinsic pathway may be impacted when blood contacted with PVC tubing. However, there was no significant difference of APTT, FIX concentration and CD62p expression rate between the two materials. Moreover, the migration in the DINCH system was considerably lower than for DEHP, which indicates that DINCH could be a promising alterative plasticizer of DEHP.     

Blood interactions with plasticised poly (vinyl chloride): influence of surface modification

Surface modification of plasticised poly (vinyl chloride) (PVC), with di-(2-ethylhexyl) phthalate (DEHP) as plasticiser, for the improvement of blood compatibility in potential clinical use such as cardiopulmonary bypass was achieved by heparinisation. The influence of surface modification on blood compatibility was assessed in terms of the influence on fibrinogen and factor XII adsorption in vitro, and the generation of thrombin-antithrombin III complex (TAT) and the complement component C3a, in vitro and ex vivo. Electron spectroscopy for chemical analysis (ESCA) was used to characterise the heparinised surface in order to correlate the surface properties with the blood response. Results indicate that at the plasticised PVC surface there is a higher content of heparin than that of the PVC and the DEHP content is lower than that present at the surface of standard plasticised PVC. The blood compatibility assessment confirms the importance of surface modification for the improvement of blood compatibility.     

Zwitterionic sulfobetaine-grafted poly(vinylidene fluoride) membrane with highly effective blood compatibility via atmospheric plasma-induced surface copolymerization

Development of nonfouling membranes to prevent nonspecific protein adsorption and platelet adhesion is critical for many biomedical applications. It is always a challenge to control the surface graft copolymerization of a highly polar monomer from the highly hydrophobic surface of a fluoropolymer membrane. In this work, the blood compatibility of poly(vinylidene fluoride) (PVDF) membranes with surface-grafted electrically neutral zwitterionic poly(sulfobetaine methacrylate) (PSBMA), from atmospheric plasma-induced surface copolymerization, was studied. The effect of surface composition and graft morphology, electrical neutrality, hydrophilicity and hydration capability on blood compatibility of the membranes were determined. Blood compatibility of the zwitterionic PVDF membranes was systematically evaluated by plasma protein adsorption, platelet adhesion, plasma-clotting time, and blood cell hemolysis. It was found that the nonfouling nature and hydration capability of grafted PSBMA polymers can be effectively controlled by regulating the grafting coverage and charge balance of the PSBMA layer on the PVDF membrane surface. Even a slight charge bias in the grafted zwitterionic PSBMA layer can induce electrostatic interactions between proteins and the membrane surfaces, leading to surface protein adsorption, platelet activation, plasma clotting and blood cell hemolysis. Thus, the optimized PSBMA surface graft layer in overall charge neutrality has a high hydration capability and the best antifouling, anticoagulant, and antihemolytic activities when comes into contact with human blood.     

Facile surface modification of silicone rubber with zwitterionic polymers for improving blood compatibility

A facile approach to modify silicone rubber (SR) membrane for improving the blood compatibility was investigated. The hydrophobic SR surface was firstly activated by air plasma, after which an initiator was immobilized on the activated surface for atom transfer radical polymerization (ATRP). Three zwitterionic polymers were then grafted from SR membrane via surface-initiated atom transfer radical polymerization (SI-ATRP). The surface composition, wettability, and morphology of the membranes before and after modification were characterized by X-ray photoelectron spectroscopy (XPS), static water contact angle (WCA) measurement, and atomic force microscopy (AFM). Results showed that zwitterionic polymers were successfully grafted from SR surfaces, which remarkably improved the wettability of the SR surface. The blood compatibility of the membranes was evaluated by protein adsorption and platelet adhesion tests in vitro. As observed, all the zwitterionic polymer modified surfaces have improved resistance to nonspecific protein adsorption and have excellent resistance to platelet adhesion, showing significantly improved blood compatibility. This work should inspire many creative uses of SR based materials for biomedical applications such as vessel, catheter, and microfluidics.     

Solution-phase surface modification in intact poly(dimethylsiloxane) microfluidic channels

An improved approach composed of an oxidation reaction in acidic H2O2 solution and a sequential silanization reaction using neat silane reagents for surface modification of poly(dimethylsiloxane) (PDMS) substrates was developed. This solution-phase approach is simple and convenient for some routine analytical applications in chemistry and biology laboratories and is designed for intact PDMS-based microfluidic devices, with no device postassembly required. Using this improved approach, two different functional groups, poly(ethylene glycol) (PEG) and amine (NH2), were introduced onto PDMS surfaces for passivation of nonspecific protein absorption and attachment of biomolecules, respectively. X-ray electron spectroscopy and temporal contact angle experiments were employed to monitor functional group transformation and dynamic characteristics of the PEG-grafted PDMS substrates; fluorescent protein solutions were introduced into the PEG-grafted PDMS microchannels to test their protein repelling characteristics. These analytical data indicate that the PEG-grafted PDMS surfaces exhibit improved short-term surface dynamics and robust long-term stability. The amino-grafted PDMS microchannels are also relatively stable and can be further activated for modifications with peptide, DNA, and protein on the surfaces of microfluidic channels. The resulting biomolecule-grafted PDMS microchannels can be utilized for cell immobilization and incubation, semiquantitative DNA hybridization, and immunoassay.     

等离子体表面接枝改性聚对苯二甲酸乙二醇酯的血液相容性研究

利用等离子体表面接枝改性方法在聚对苯二甲酸乙二醇酯(polyethylene terephthalate，PET)材料表面接枝不同分子量的聚乙二醇(PEG)，体外血液相容性实验表明．接枝了PEG的PET材料的血液相容性与PEG的分子量有关；当接枝的PEG分子量达到6000时，材料的血液相容性最好。     

Surface modification of polystyrene and poly(ethylene terephtalate) by grafting poly(N-isopropylacrylamide)

In this work, poly(N-isopropylacrylamide) (PNIPAAm) was incorporated into previously oxidized PS and PET surfaces by grafting using two photo-initiation pathways. The incorporation of PNIPAAm was observed by drop water contact angle measurements, dyeing with Methylene Blue and AFM images analysis of the virgin and modified polymers. It was verified that the grafting process depends on the chemical surface environment. The grafted surfaces are hydrophilic below 32 °C and hydrophobic above this temperature. The transition is due to the incorporated PNIPAAm. This characteristic gives to the grafted materials potential to be applied as biomaterials.     

Chemical surface modification of poly (ethylene terephthalate) by excimer irradiation of high and low intensities

Poly (ethylene terephthalate) (PET) was modified by a KrF 248 nm excimer laser with high- (above ablation threshold) and low- (below ablation threshold) fluence. The PET surface develops usually a periodic roughness or ripples with high fluence. The roughness size is in the micron range and the surface shows signs of global melting. However, the ripple size can be reduced to sub-micron level by an irradiation of the sample below the ablation threshold with a polarized beam. The morphology of the irradiated surfaces was examined by scanning electron microscopy (SEM). Chemical surface changes of the materials were characterized by X-ray photoelectron spectroscopy (XPS). The PET modification by high fluence will normally results in the deposition of some yellow to black materials (debris), on the treated surface. The debris are ionized and from carbon rich materials which finally condense forming higher aggregates, resulting in a reduction of O/C ratio. By contrast, modification of PET surfaces by low fluence leads to an oxidation and almost no ablation is detected. The increase of oxygen concentration on low fluence modified surfaces is probably due to a subsequent reaction with atmospheric O₂ during irradiation. Our work suggests that a careful selection of laser parameters for the surface modification of polymer is of primary importance. Received: 06 November 2000 / Reviewed and accepted: 07 November 2000     

In vitro blood compatibility of heparin-immobilized polyurethane containing ester groups in the side chain

In a previous study, we reported on the synthesis of heparin-immobilized polyetherurethanes containing ester groups in the side chain. In this study, the blood compatibility of heparin-immobilized polyurethanes was investigated using in vitro plasma recalcification time (PRT), activated partial thromboplastin time (APTT), platelet adhesion and activation and peripheral blood mononuclear cell (PBMC) adhesion and activation. In the experiment with plasma proteins, the PRT of the polyurethane (PU) surface was prolonged by polyethylene oxide (PEO) grafting and further prolonged by heparin immobilization. The APTT was prolonged on the PU-C-H and PU-P-H, suggesting the binding of immobilized heparin to the antithrombin III. The percentage of platelet adhesion on the PU was almost the same as that on carboxylic acid-introduced PU (PU-C), but was slightly decreased by PEO grafting and further decreased by heparin immobilization. The release of serotonin from the adhering platelets was slightly suppressed on the PEO-grafted PU yet significantly suppressed on the heparin-immobilized PUs. In the PBMC experiments, the adhesion and activation of the cells were significantly suppressed on the heparin-immobilized PUs, and the amount of interleukin-6 (IL-6) released from the PBMCs stimulated with the surface-modified PUs decreased with a decrease in the PBMC adhesion.     

In vitro bio-immunological and cytotoxicity studies of poly(2-oxazolines)

Poly(2-oxazolines) with varying alkyl chain lengths (e.g., methyl, ethyl, aryl) and molar masses have been tested for cell cytotoxicity in vitro. A standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used for the estimation of cell viability. Two monomers, 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline, were found to provide polymers with non-cytotoxic properties. The dependence of cell viability on molar mass confirmed the expected trend; the viability increased with the higher molar mass of poly(2-ethyl-2-oxazoline) (PETOX), up to 15,000 g/mol. The results obtained for the polymers with aliphatic side chains were compared with the analogues that possessed an aromatic moiety. All results confirmed low cytotoxicity of the polymers prepared by cationic polymerization of 2-alkyl- and 2-aryl-2-oxazolines, which supports their utilization in biomedical applications. Fluorescence microscopy and steady-state fluorescence were used to observe pyrene-labeled polymer interactions with living cells. Polymer accumulated within the cells was found to be dependent on polymer concentration in media. The immunoefficiency of aromatic and aliphatic oxazoline polymers and copolymers was also studied. Phagocytic and metabolic activities of macrophages were used to assess the immunosuppressive effects of the selected copolymers for possible applications in drug delivery and immunobiology. Overall, the tested polymers demonstrated no significant influences on the cellular immunological parameters.     

Poly(dimethylsiloxane) surface modification by plasma treatment for DNA hybridization applications

In this work, the surface modification of poly(dimethylsiloxane) (PDMS) was carried out by using a 2-step plasma modification with Ar followed by acrylic acid (AAc). The optimal conditions were found to be 0.5 min with Ar at 0.7 mbar; and 5 min with AAc at 0.2 mbar. The water contact angle (WCA) of the native PDMS decreased from 110 degrees to 30 degrees after modification, then stabilized to values between 50 degrees to 60 degrees after 1 day exposure to air. The stability of the modified PDMS was further improved by Soxhlet-extracting the PDMS with hexane prior to plasma treatment. Atomic force microscopy (AFM) showed significant changes in surface morphology after the 2-step plasma modification. X-ray photoelectron (XPS) spectroscopy further confirmed the successful modification of the PDMS surface with PAAc, by exhibiting C1s peaks at 285.9 eV, 287.4 eV and 289.9 eV, originating from C-O, C=O and O-C=O moieties, respectively. Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy of the poly(acrylic acid) (PAAc) modified PDMS surface showed a distinctive peak at 1715 cm(-1), attributed to the presence of COOH groups from the PAAc. The carboxyl peak on the spectra of the PAAc modified PDMS was quite stable even after storage at room temperature in phosphate buffer saline (PBS) and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer for 17 h. 5'-amino-terminated oligonucleotides were covalently attached to the PAAc modified PDMS surface via carbodiimide coupling. Subsequently, fluorescently tagged complementary oligonucleotides were successfully hybridized to this surface, as determined by fluorescence microscopy.     

In vitro degradation of poly(ester-urethanes) for biomedical applications

Degradation studies on a series of polyesterurethanes having different compositions of hard and soft blocks have been performed utilizing an accelerated test method. Degradation was followed by titrimetry, mass loss, mechanical properties and infrared spectroscopy. As the number of methylene groups present within the polyester moiety was increased, the resistance to degradation also increased. The presence of an aromatic component in the hard block reduced the rate of hydrolysis but the degradation in mechanical properties was accelerated.     

In vitro predegradation at elevated temperatures of poly(lactide)

In this study in vitro predegradation at elevated temperatures, used to obtain an increased degradation rate, was investigated. The in vitro degradation was followed by mass loss, molecular weight loss and changes in thermal properties. Two biodegradable polymers, the homopolymer PLLA and a copolymer PLA96 (96% L4%D lactide), were hydrolytically degraded at 90°C in a phosphate buffered solution. Both polymers, PLLA and PLA96, showed an initial linear degradation rate, but with longer implantation periods the degradation rate decreased and total degradation was best described as an asymptotic. Mass loss of the copolymer PLA96 was twice that of PLLA. The chemical analysis of the in vitro predegraded polymers coincided for both the decrease in molecular weight and the thermal properties with physiologically degraded poly(lactide). The results of this study show that although the degradation temperature is well above the glass transition temperature and not comparable to physiological temperatures, there seems to be good correlation between the in vitro degraded material and physiologically degraded material. In vitro predegradation enables investigation of the entire degradation process of a polymer in a short-term study. Moreover, in vitro predegradation allows direct comparison of the degradation rate of various polymers.     

In vitro adhesion and biocompatability of osteoblast-like cells to poly(methylmethacrylate) and poly(ethylmethacrylate) bone cements

A bone cement, poly(ethylmethacrylate)/n-butylmethacrylate (PEMA/nBMA) has been developed with lower exotherm and monomer leaching compared to the traditional poly(methylmethacrylate)/methylmethacrylate (PMMA/MMA) cement. This study compares the in vitro biological response to the cements using primary human osteoblast-like cells (HOB). Cell attachment was qualified by immunolocalization of vinculin and actin cytoskeleton, showing more organization on PEMA/nBMA compared to PMMA/MMA. Proliferation was assessed using tritiated thymidine incorporation, and phenotype expression determined by measuring alkaline phosphatase (ALP) activity. An increase in proliferation and ALP activity was observed on PEMA/nBMA compared to PMMA/MMA. The results confirm the biocompatability of PEMA/nBMA, and an enhanced cell attachment and expression of differentiated cell phenotype.     

Surface modification of poly(tetrafluoroethylene) by magnesium amalgam

Mg amalgam reacts with PTFE (foil or oriented film on Si) to give a thin surface layer containing MgF₂ in a mixture with complicated, air-sensitive, carbonaceous product containing large amount of residual C-F bonds. The reaction does not propagate into the bulk polymer, which, consequently, retains its white color even after hundreds of hours of reaction at 150 °C. These findings contrast with the reactivity of PTFE with amalgams of alkali metals, Li, Na, K. The differences are interpreted, in terms of the electrochemical model of amalgam carbonization, as blocking of charge (e^–/Mg ²⁺) propagation through the modified layer. AFM patterns show that the Mg-treatment increases the surface roughness. The molecular-level ordering of PTFE films is strongly perturbed by the action of Mg-amalgam; the treated surface shows only small proportion of organized macromolecules.     

CVDP制备的聚对亚苯基二亚甲基的表面磺化改性

采用化学气相沉积聚合(CVDP)的方法制备了聚对亚苯基二亚甲基(PPX)涂层,再通过发烟硫酸的化学表面改性成功地在PPX的芳香环上引入磺酸基团,可作为进一步功能化的反应基团.与PPX相比,表面磺化改性PPX(PPX-SO3Na)的接触角变小,亲水性增加,更有利于作为生物医用材料.采用原子力显微镜(AFM)测定PPX和磺化PPX的表面形貌,结果表明,表面磺化改性后的PPX变得更光滑,更有利于作抗凝血涂层材料.Fenton试剂测得PPX-SO3Na的抗化学氧化时间略低于PPX,但由于膜的主链主要是由苯环连接而成的,相对其它常用聚合物来说依然具有较好的抗化学氧化性能.     

Surface modification of poly(ethylene terephthalate) by plasma polymerization of poly(ethylene glycol)

Poly(ethylene glycol) (PEG) was ‘polymerized’ onto poly(ethylene terephthalate) (PET) surface by radio frequency (RF) plasma polymerization of PEG (average molecular weight 200 Da) at a monomer vapour partial pressure of 10 Pa. Thin films strongly adherent onto PET could be produced by this method. The modified surface was characterized by infra red (IR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), cross-cut test, contact angle measurements and static platelet adhesion studies. The modified surface, believed to be extensively cross-linked, however showed all the chemical characteristics of PEG. The surface was found to be highly hydrophilic as evidenced by an interfacial free energy of about 0.7 dynes/cm. AFM studies showed that the surface of the modified PET became smooth by the plasma polymerized deposition. Static platelet adhesion studies using platelet rich plasma (PRP) showed considerably reduced adhesion of platelets onto the modified surface by SEM. Plasma ‘polymerization’ of a polymer such as PEG onto substrates may be a novel and interesting strategy to prepare PEG-like surfaces on a variety of substrates since the technique allows the formation of thin, pin-hole free, strongly adherent films on a variety of substrates.     

软骨细胞在聚乳酸支架中的体外生长行为

采用明胶和氯化钠颗粒作为致孔剂,使用溶剂浇铸／颗粒沥滤法制备了高孔隙率、孔间连通和高机械性能的聚乳酸支架,采用软骨细胞体外培养研究了这两种多孔支架对细胞生长性能的影响．结果表明,软骨细胞在以明胶颗粒为致孔剂制备的多孔支架中的相对数量和GAG的分泌量更多,细胞的活性更高。     

有机玻璃表面的静电自组装超亲水防雾改性

研究利用聚烯丙基胺盐酸盐与SiO2纳米粒子在有机玻璃片表面的静电自组装来进行超亲水防雾改性。水接触角分析显示随着双电层数目的增加,有机玻璃的亲水性明显改善,并在20双电层时呈现超亲水性。原子力显微镜观察表明,有机玻璃片的超亲水性与其表面形成规整排列的纳米微孔结构,有利于水汽在有机玻璃片表面形成水膜有关。防雾测试结果进一步表明,表面自组装改性能明显改善有机玻璃片的防雾性能。此外,透光率分析结果还得出有机玻璃片改性后并不影响其透光性,反而还会因为反射光强减弱而略微提高。