Stainless steel modified with poly(ethylene glycol) can prevent protein adsorption but not bacterial adhesion

The surface of AISI 316 grade stainless steel (SS) was modified with a layer of poly(ethylene glycol) (PEG) (molecular weight 5000) with the aim of preventing protein adsorption and bacterial adhesion. Model SS substrates were first modified to introduce a very high density of reactive amine groups by the adsorption of branched poly(ethylenimine) (PEI) from water. Methoxy-terminated aldehyde-poly(ethylene glycol) (M-PEG-CHO) was then grafted onto the PEI layers using reductive amination at the lower critical solution temperature (LCST) of the PEG in order to optimize the graft density of the linear PEG chains. The chemical composition and uniformity of the surfaces were determined using X-ray photoelectron spectroscopy (XPS) and time-of-flight static secondary ion mass spectrometry (ToF-SSIMS) in the imaging mode. The effects of PEI concentration and different substrate pre-cleaning methods on the structure and stability of the final PEG layer was examined. Piranha solution proved to be the most effective method for removing adventitious hydrocarbon contamination, compared to cleaning with ultrasonication in organic solvents, and was the SS substrate that produced the most stable and thickest PEI layer. The surface density of PEI was shown to increase with increasing PEI concentration (up to 30 mg/ml), as determined from XPS measurements, and subsequently produced the PEG layer with the highest density of attached chains. In model experiments using β-lactoglobulin no protein adsorption was detected on the optimized PEG surface as determined by XPS and ToF-SSIMS analysis. However, neither the adhesion of a Gram-negative (Pseudomonas sp.) nor a Gram-positive (Listeria monocytogenes) bacterium was affected by the coating as equal numbers adhered to all surfaces tested. Our results show that preventing protein adsorption is not a prerequisite stopping bacterial adhesion, and that other mechanisms most likely play a role.     

Preparation and Characterization of Chitosan Composite Membranes Crosslinked by Carboxyl-capped Poly（ethylene glycol）

In this study a series of chemically crosslinked chitosan/poly（ethylene glycol） （CS/PEG） composite membranes were prepared with PEG as a crosslinking reagent other than an additional blend. First, carboxyl-eapped poly（ethylene glycol） （HOOC-PEG-COOH） was synthesized. Dense CS/PEG composite membranes were then prepared by casting/evaporation of CS and HOOC-PEG-COOH mixture in acetic acid solution. Chitosan was chemically crosslinked due to the amidation between the carboxyl in HOOC-PEG-COOH and the amino in chitosan under heating, as confirmed by FTIR analysis. The hydrophilicity, water-resistance and mechanical properties of pure and crosslinked chitosan membranes were characterized, respectively. The results of water contact angle and water absorption showed that the hydrophilicity of chitosan membranes could be significantly improved, while no significant difference of weight loss between pure chitosan membranes and crosslinked ones was detected, indicating that composite membranes with amidation crosslinking possess excellent water resistanance ability. Moreover, the tensile strength of chitosan membranes could be significantly enhanced with the addition of certain amount of HOOC-PEG-COOH crosslinker, while the elongation at break didn＇t degrade at the same time. Additionally, the results of swelling behaviors in water at different pH suggested that the composite membranes were pH sensitive.     

Strategies toward biocompatible artificial implants: Grafting of functionalized poly(ethylene glycol)s to poly(ethylene terephthalate) surfaces

Epoxide and aldehyde end‐functionalized poly(ethylene glycol)s (PEGs) (M_w = 400, 1000, 3400, 5000, and 20,000) were grafted to poly(ethylene terephthalate) (PET) film substrates that contained amine or alcohol groups. PET‐PAH and PET‐PEI were prepared by reacting poly(allylamine) (PAH) and polyethylenimine (PEI) with PET substrates, respectively; PET‐PVOH was prepared by the adsorption of poly(vinyl alcohol) (PVOH) to PET substrates. Grafting was characterized and quantified by the increase of the intensity of the PEG carbon peak in the X‐ray photoelectron spectra. Grafting yield was optimized by controlling reaction parameters and was found to be substrate‐independent in general. Graft density consistently decreased as PEG chain length was increased. This is likely due to the higher steric requirement of higher molecular weight PEG molecules. Water contact angles of surfaces containing long PEG chains (3400, 5000, and 20,000) are much lower than those containing shorter PEG chains (400 and 1000). This indicates that longer PEG chains are more effective in rendering surfaces hydrophilic. Protein adsorption experiments were carried out on PET‐ and PEG‐modified derivatives using collagen, lysozyme, and albumin. After PEG grafting, the amount of protein adsorbed was reduced in all cases. Trends in surface requirements for protein resistance are: surfaces with longer PEG chains and higher chain density, especially the former, are more protein resistant; PEG grafted to surfaces containing branched or network polymers is not effective at covering the underlying substrate, and thus does not protect the entire surface from protein adsorption; and substrates containing surface charge are less protein‐resistant. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5389–5400, 2004     

Surface Modification of Chitosan Films-Grafting Ethylene Glycol Oligomer and Its Effect on Protein Adsorption

This work is a part of a series on surface modification of materials made of chitosan. This report focused on grafting monomethoxy ethylene glycol oligomers (mPEG) on the surface of chitosan films. The chemical reactions were performed by immersing the films in organic solvent containing aldehyde derivative of mPEG. The presence of ethylene glycol moieties was determined by attenuated total reflectance-infrared spectroscopy (ATR-IR) and nuclear magnetic resonance (NMR). The hydrophobicity of the modified surface, determined by air-water contact angle, decreased when the ethylene glycol derivatives were grafted on the film. The modified films were also subjected to protein adsorption study in order to assess their uses in biomedical applications. It was found that the presence of ethylene glycol units reduced the adsorption of proteins (albumin and lysozyme) on the films. We therefore have shown that manipulation of the interaction between chitosan and bio-macromolecules is possible by chemically modifying the surface of chitosan.     

Surface modification and characterization of thermoplastic polyurethane

This work reports the modification of thermoplastic polyurethanes (TPUs) in order to enlarge their application range, for example, as biomaterials by increasing its hydrophilicity.A TPU was successfully modified by using three different strategies: ultra-violet irradiation (UV), gamma irradiation (GI) and interfacial modification (IM). The results suggested the possibility of modifying the polyurethane-based surface either with poly(ethylene glycol) (PEG) or hydroxylethyl methacrylate (HEMA) or hexamethylene diamine (HMD) or chitosan (CT) by using any of these methods. The properties of the grafted PU were evaluated by surface, structural and thermal analysis. The results suggest that, among the methods studied in this work, the modification by gamma irradiation (GI) seems to be the most promising, since this method gives high values of grafting yield and has the advantage of providing a clean modification, meaning that no initiator is needed.     

Surface modification of calcium carbonate nanofillers by fluoro- and alkyl-alkoxysilane: Consequences on the morphology,thermal stability and gas barrier properties of polyvinylidene fluoride nanocomposites

Nano-sized precipitated silica coated calcium carbonate fillers (PCC-Si) were modified by an alkyl- and a fluoro-alkoxysilane derivative, respectively. PCC-Si surface modification was characterized by elemental analysis, Fourier transform infrared analysis and X-ray photoelectron spectroscopy. The modification conditions used for surface treatment led to a similar grafting density (around 3.2 μmol m^?2) for the two alkoxysilane derivatives. A significant decrease of filler hydrophilicity was observed after the alkoxysilane treatment. Nanocomposites prepared by melt mixing the modified fillers (10 wt.%) with polyvinylidene fluoride (PVDF) depicted no color change, an enhanced filler dispersion state with an homogeneous dispersion of very small filler aggregates (less than 150 nm diameter size), an increase of the thermal stability at high temperature and no change of the PVDF crystalline morphology. The oxygen permeability decrease measured on the nanocomposite prepared from the perfluorooctyltriethoxysilane modified filler was in good agreement with Maxwell law. The permeability increase evidenced for the nanocomposite based on the octyltriethoxysilane modified PCC suggested the formation of weak interfaces in this system.     

Surface immobilization of poly(ethylene oxide): Structure and properties

We covalently immobilized poly(ethylene oxide) (PEO) chains onto a fluorinated ethylene propylene copolymer (FEP) surface. On the FEP surface, aldehyde groups were first deposited by plasma polymerization of acetaldehyde or acrolein. Then, amino‐PEO chains were immobilized through Schiff base formation, which was followed by reduction stabilization with sodium cyanoborohydride. The PEO‐grafted polymer surfaces thus prepared were characterized by X‐ray photoelectron spectroscopy (XPS), atomic force microscopy, contact‐angle measurements, and protein adsorption. The dramatic increase in the C O intensity of the high‐resolution XPS C 1s spectrum, together with an overall increase in oxygen content, indicated the successful attachment of PEO chains onto the acetaldehyde plasma surfaces. The amount of grafted PEO chains depended on the superfacial density of the plasma‐generated aldehyde groups. The grafted monoamino‐PEO chains formed a brushlike structure on the polymer surface, whereas the bisamino‐PEO chains predominately adopted a looplike conformation. The PEO surface had a regular morphology with greater roughness than the aldehyde surface underneath. Surface hydrophilicity increased with the grafting of PEO. Also, the bisamino‐PEO‐grafted surface had slightly higher surface hydrophilicity than its monoamino‐PEO counterpart. These PEO coatings reduced fibrinogen adsorption by 43% compared with the substrate FEP surface. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2323–2332, 2000     

以PEG为间隔基固定赖氨酸制备血液相容的聚氨酯材料

通过多步表面改性方法制备了血液相容性好的聚氨酯材料. 以PEG为间隔基将ε-赖氨酸通过Schiff碱反应和进一步的还原反应连接于聚氨酯表面. 该表面的水接触角和XPS结果表明, PEG和ε-赖氨酸成功接枝. 用蛋白质吸附和血栓溶解实验对材料的血液相容性进行了研究. 蛋白质吸附结果表明, 相对于改性前的聚氨酯, ε-赖氨酸改性后的表面能减少纤维蛋白原的吸附量近80%. 血栓溶解测试结果显示, ε-赖氨酸改性后的表面能够在13 min内使初生的血栓溶解. 这些结果证实, 改性后的表面不仅能抑制非特异性蛋白质的吸附, 而且在测试条件下能溶解初生的血栓.     

Amphiphilic PPESK-g-PEG graft copolymers for hydrophilic modification of PPESK microporous membranes

Amphiphilic graft copolymers comprising poly(phthalazinone ether sulfone ketone) (PPESK) backbones and poly(ethylene glycol) (PEG) side chains were synthesized and blended into PPESK casting solutions to prepare hydrophilic and anti-fouling microporous membranes. The graft copolymer was prepared by a modified Williamson etherification method. Sodium alkoxide of methoxyl PEG (PEG-ONa) was used to react with chloromethylated PPESK (CMPPESK). FT-IR spectroscopy, ¹H NMR and solid-state ¹³C CP-MAS NMR analysis confirmed the covalent linking of PEG with PPESK backbones. The incorporation ratio of PEG calculated from ¹H NMR was in agreement with that from TGA tests. The graft products were added into PPESK casting solutions to prepare composite porous membranes using phase inversion method. X-ray photoelectron spectroscopy (XPS) and water contact angle examinations indicated that the grafting copolymers were preferentially excluded to the membrane-coagulant interface during membrane forming, contributing the membranes with improved hydrophilicity and surface wettability. Compared with the neat membrane, the blend membranes exhibited a larger surface pore size and less susceptible to protein fouling.     

In-vitro hemocompatibility evaluation of a thermoplastic polyurethane membrane with surface-immobilized water-soluble chitosan and heparin

The surface of a thermoplastic polyurethane (TPU) membrane was treated with low temperature plasma (LTP) and was then grafted with poly(acrylic acid) (PAA), followed by the grafting of water-soluble chitosan (WSC) and heparin (HEP). The surface was characterized with static contact-angle and X-ray photoelectron spectroscopy (XPS). The results showed that the surface densities of peroxides and PAA reached a maximum when treated with LTP for 90 s. A higher pH of the reacting solution led to higher graft densities of WSC and HEP. After WSC and HEP grafting, the hydrophilicity of the TPU membrane was increased. The adsorption of proteins on HEP-grafted TPU membranes was effectively curtailed. In addition, HEP grafting also reduced platelet adhesion, elevated thrombin inactivation, and prolonged the blood coagulation time. According to the L929 fibroblast cell growth inhibition index, the HEP-grafted TPU membranes exhibited non-cytotoxicity. Overall results demonstrated that the HEP immobilization could not only improve the hydrophilicity but also the hemocompatibility of the TPU membrane, while maintaining the ascendant biocompatibility.     

Antibacterial activity of pH‐sensitive genipin cross‐linked chitosan/poly(ethylene glycol)/silver nanocomposites

Novel nanocomposites consisting of genipin cross‐linked chitosan (GC), poly(ethylene glycol) (PEG), and silver nanoparticles were prepared for such biomedical applications as the wound‐healing materials. Various amounts of silver nanoparticles were dispersed in the GC/PEG hydrogel matrix without severe aggregation. The effects of composition and silver nanoparticles on the physico‐chemical properties of samples were evaluated by infrared analysis, contact angle measurements, and swelling tests. The GC/PEG/Ag nanocomposite showed a pH‐sensitive swelling behavior. The surface hydrophilicity of GC/PEG/Ag nanocomposites was improved with the increase of silver nanoparticle content. L929 cell attachment was improved in the presence of silver nanoparticles. The antimicrobial function was assessed for the GC/PEG/Ag nanocomposites containing the silver content over 100 ppm. The silver nanoparticles had the dual functions of reinforcing structural stability and enhancing antimicrobial activity of GC/PEG/Ag nanocomposites. Copyright © 2010 John Wiley & Sons, Ltd.     

聚己内酯聚醚嵌段共聚物和共混物的表面性质对其药物释放行为的影响

聚己内酯聚醚嵌段共聚物和共混物的表面性质对其药物释放行为的影响王卫华，贝建中，王智峰，王身国（中国科学院化学研究所北京１０００８０）关键词聚己内酯聚醚嵌段共聚物，共混物，电子能谱，表面性质，药物释放行为聚己内醋（ＰＣＬ）具有优良的药物通透性和生物相容...     

Enhanced Cu(II) and Cr(VI) biosorption capacity on poly(ethylenimine) grafted aerobic granular sludge

The biosorption characteristics of cations and anions from aqueous solution using polyethylenimine (PEI) modified aerobic granules were investigated. Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis exhibit the presence of PEI on the granule surface. Compared with the raw granule, the modified aerobic granules with PEI showed a significant increase in sorption capacity for both metal ions. The monolayer biosorption capacity of granules for Cu(II) and Cr(VI) ions was found to be 71.239 and 348.125mg/g. The optimum solution pH for adsorption of Cu(II) and Cr(VI) from aqueous solutions was found to be 6 and 5.2, respectively. The biosorption data fitted better with the Redlich-Peterson isotherm model. FTIR showed chemical interactions occurred between the metal ions and the amide groups of PEI on the biomass surface. XPS results verified the presence of Cr(III) on the biomass surface, suggesting that some Cr(VI) anions were reduced to Cr(III) during the sorption.     

Surface bio-modification of poly(hydroxybutyrate-co-hydroxyhexanoate) and its aging effect

In this work, poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) film was fabricated by a solution-casting method and subsequently was modified by NaOH treatment to improve the surface hydrophilic property. Surface properties including hydrophilicity, surface appearance and functional groups were characterized by water contact angle measurement, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The results showed the hydrophilicity of PHBHHx film was obviously improved by the NaOH treatment due to the topography changes promoted by the NaOH-etching and the introduction of polar groups included hydroxyl and carboxyl on the topmost surface layers. However, the modified film exhibited an aging effect: the hydrophilicity decreases with time elapsed during storage. It was found that the aging rate was strongly dependent on the crystallinity of the film and the storage environment. The sample with high-crystallinity lost hydrophilic property slower than that with low-crystallinity. Hydrophilic and low-temperature environment also prevented the modified PHBHHx from fast losing of the hydrophilicity.     

Preparation and characterization of polyethyleneimine modified ion-exchanger based on poly(methacrylate-co-ethylene dimethacrylate) monolith

A polyethyleneimine (PEI) modified ion-exchanger was prepared based on poly(methacrylate-co-ethylene dimethacrylate) monolith cast in 100 mm x 4.6 mm I.D. stainless steel tube with heptane as the porogenic solvent at 65 degrees C for 12 h. The pores larger than 500 nm presented 85% of total pore volume of PEI monolith and provided the better permeability for separation. Bovine serum albumin (BSA) binding capacity on the column was enhanced with increasing the molecular weight of PEI, indicated that the brush ligand emanated from the surface and captured more protein by multiple binding sites. Titration experiment as well as BSA retention versus the pH of mobile phase showed that the monolith exhibited weak ion-exchange property, and recovered BSA on the monolith reached 97% when NaCl content in mobile phase was higher than 0.5 M. Frontal analysis and gradient elution of BSA indicated that PEI monolith provided the rapid mass transfer in chromatographic procedure, which made the dynamic binding capacities as well as column efficiency keep as constants at high operating flow rate. Fast separation of three mode proteins mixture (lysozyme, hemoglobin and BSA) on the monolith was achieved within 3 min at velocity of 1445 cm/h. This demonstrated the potential of PEI monolith for the rapid analysis and separation of proteins.     

Kinetic study of chitosan‐tripolyphosphate complex reaction and acid‐resistive properties of the chitosan‐tripolyphosphate gel beads prepared by in‐liquid curing method

Chitosan gel beads were prepared using an in‐liquid curing method by the ionotropic crosslinking with sodium tripolyphosphate. Crosslinking characteristics of the chitosan‐TPP beads were improved by the modification of in‐liquid curing mechanism of the beads in TPP solution. Chitosan gel beads cured in pH value lower than 6 were really ionic‐crosslinking controlled, whereas chitosan gel beads cured in pH values higher than 7 were coacervation‐phase inversion controlled accompanied with slightly ionic‐crosslinking dependence. According to the result, significantly increasing the ionic‐crosslinking density of chitosan beads could be achieved by transferring the pH value of the curing agent, TPP, from basic to acidic. The swelling behavior of various chitosan beads in acid appeared to depend on the ionic‐crosslinking density of the chitosan‐TPP beads that were deeply affected by the curing mechanism of the beads. The mechanism of chitosan‐TPP beads swollen in weak acid was chain‐relaxation controlled, while the mechanism of chitosan‐TPP beads swollen in strong acid seem to be not only chain‐relaxation but also chain‐scission controlled. Chitosan‐TPP beads prepared in acidic TPP solution decreased the chain‐scission ability due to the increase of ionic crosslinking density of the beads. By the transition of curing mechanism, the swelling degree of chitosan‐TPP beads was depressed, and the disintegration of chitosan‐TPP beads would not occur in strong acid. The mechanism of ionic‐crosslinking reaction of chitosan beads could be investigated by an unreacted core model, and the curing mechanism of the chitosan beads is mainly diffusion controlled when higher than 5% of chitosan was employed. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1551–1564, 1999     

Surface Heparinization of Poly(ether ether ketone)

Photo-grafting of hydrophilic monomer and space arms was used to enhance the hydrophilicity of poly(ether ether ketone)(PEEK) with the aim of extending its application to biological fields. PEEK films were surface modified by UV grafting of acrylic acid(AA) to introduce ―COOH on PEEK surface. Adipic amine was used as a space arm to introduce heparin on PEEK surface based on the condensation reaction between ―NH₂ and ―COOH. The modified PEEK(PEEK-COOH, PEEK-NH₂ and PEEK-Hep) was characterized by energy-disperse spectroscopy (EDS), X-ray photoelectron spectroscopy(XPS) and water contact angle measurements, which show that heparin was grafted on PEEK surface. The contact angles of modified PEEK films were lower than those of original films, demonstrating a significant improvement of surface hydrophilicity.     

Enhancement of Resistance to Protein Fouling of Poly(ether imide) Membrane by Surface Grafting with PEG under Organic Solvent-free Condition

Poly(ether imide) (PEI) membrane with enhanced antifouling property was successfully prepared in a mild and simple procedure. The virgin membrane was firstly functionalized with an aqueous solution of diamino-terminated poly(ethylene oxide) block copolymer (PEG-diamine). Glutaraldehyde was used in a second step as a linker to chemically attach additional PEG-diamine to the primary amine groups grafted on PEI membrane surface. Immobilization of PEG segments was confirmed using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy. Ultrafiltration experiments revealed that the enhancement of a PEG coverage on the membrane surface provided superior anti-protein-fouling property. Cycles of protein filtration also demonstrated that the antifouling surface was stable over time and excellent ultrafiltration performance could be maintained without the need of harsh cleansing operation.     

Surface modification of polycarbonate urethane by grafting polyethylene glycol and bivalirudin drug for improving hemocompatibility

As the clinical demand for blood-contacting materials increases, higher requirements are placed on their physicochemical properties, durability and hemocompatibility in vivo. In this work, a multiple functionalized material was developed through a facile modification process. Herein, polycarbonate urethane (PCU) surface was co-modified with polyethylene glycol (PEG) and bivalirudin (BVLD). PCU provides excellent physical and mechanical properties, PEG and BVLD, especially BVLD, enable the surface with outstanding anticoagulant capacity. Specifically, PCU surface was first treated with hexamethylene diisocyanate to introduce active isocyanate groups onto the surface, followed by hydroxy-PEG grafting to improve the hydrophilicity. Finally, BVLD was immobilized on the surface via Michael addition reaction to improve antithrombotic properties. Attenuated total reflection Fourier transforms infrared spectroscopy and UV spectrophotometers were used to confirm the modified surfaces. The hydrophilicity was characterized by static water contact angle measurement, the morphology of the modified surfaces was observed by scanning electron microscopy. Blood compatibility of the modified surfaces was characterized by the hemolysis rate, platelet adhesion assay and cell culture test. The results showed that the BVLD immobilized surface has excellent anticoagulant properties, good fibrin-bound thrombin inhibition, and good resistance against non-specific adhesion of proteins. Hence, the co-modification with PEG and BVLD was proved an encouraging strategy for improving hemocompatibility.     

Surface-grafted polystyrene beads with comb-like poly(ethylene glycol) chains: preparation and biological application

We prepared surface-grafted polystyrene (PS) beads with comb-like poly(ethylene glycol) (PEG) chains. To accomplish this, conventional gel-type PS beads (35-75 microm) were treated with ozone gas to introduce hydroperoxide groups onto the surface. Using these hydroperoxide groups, poly(methyl methacrylate) (PMMA, Mn= 22,000-25,000) was grafted onto the surface of the PS beads. The ester groups of the grafted PMMA were reduced to hydroxyl groups with lithium aluminum hydride (LAH). After adding ethylene oxide (EO) to the hydroxyl groups, we obtained the PS-sg-PEG beads, which had a rugged surface and a diameter of 80-150 microm. We could obtain several kinds of the PS-sg-PEG beads by controlling the chain lengths of the grafted PMMA and the molecular weights of the PEG chains. The grafted PEG layer was about 30-50 microm thick, which was verified from the cross-sectioned views of the fluorescamine-labeled beads. These fluorescence images proved that the beads possessed a pellicular structure. Furthermore, we found that the surface-grafted PEG chains had the characteristic property of reducing non-specific protein adsorption on the beads.