Lysine-PEG-modified polyurethane as a fibrinolytic surface: Effect of PEG chain length on protein interactions, platelet interactions and clot lysis

Li, Dan; Chen, Hong; McClung, W. Glenn; Brash, John L.

doi:10.1016/j.actbio.2009.03.001

Cited by 107 publications

(67 citation statements)

References 22 publications

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“…[41] It was concluded that lysinated surfaces with PEG spacers of relatively short length adsorb plasminogen more rapidly than those with longer PEG, although the ultimate adsorbed quantities are the same, and correspondingly, the surface with the greater plasminogen binding capacity lyzed clot more rapidly.…”

Section: Regulation Of Specific Protein/surface Interactions By Surfamentioning

confidence: 99%

Surface Modification to Control Protein/Surface Interactions

Lin

et al. 2011

Macromolecular Bioscience

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Protein/surface interactions are well known to play an important role in various biological phenomena and to determine the ultimate biofunctionality of a given material once it is in contact with a biological environment. Control over the interactions between proteins and material surfaces are not only of great theoretical interest but also of crucial importance for many biomedical applications. In this Feature Article, we summarize various successful approaches used in our laboratory and other groups for controlling protein adsorption through chemical modification of the surface and/or the introduction of specific topographic features. Some perspectives on future research in these areas are also presented.

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Section: Regulation Of Specific Protein/surface Interactions By Surfamentioning

confidence: 99%

Surface Modification to Control Protein/Surface Interactions

Lin

et al. 2011

Macromolecular Bioscience

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“…The reduced platelet adhesion should be attributed to the surface introduction of the PEG chains and carboxylic groups, and thus resulted in increased hydrophilicity and relatively low BFG adsorption for the composite membranes. 26,27,30 Both the outspread and the pseudopodium deformation of the platelet were obviously suppressed for the composite membranes, which indicated that the blood compatibility of the PES/PU composite membranes was improved significantly.…”

Section: Resultsmentioning

confidence: 93%

“…24,25 Its superior resistance to nonspecific protein adsorption may attribute to the lack of ionic charge, high hydrophilicity, flexibility, and mobility in the aqueous environment. 26,27 The immobilization of PEG onto a material surface to form a hydrophilic layer is an effective way to improve antifouling property. Citric acid (CA), an important weak acid, is widely used in food and biomedical industry.…”

Section: Introductionmentioning

confidence: 99%

Hemocompatible polyethersulfone/polyurethane composite membrane for high-performance antifouling and antithrombotic dialyzer

Yin

Cheng

Qin

et al. 2014

J. Biomed. Mater. Res.

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Researches on blood purification membranes are fuelled by diverse clinical needs, such as hemodialysis, hemodiafiltration, hemofiltration, plasmapheresis, and plasma collection. To approach high-performance dialyzer, the integrated antifouling and antithrombotic properties are highly necessary for the design/modification of advanced artificial membranes. In this study, we propose and demonstrate that the physical blend of triblock polyurethane (PU) and polyethersulfone (PES) may advance the performance of hemodialysis membranes with greatly enhanced blood compatibility. It was found that the triblock PU could be blended with PES at high ratio owing to their excellent miscibility. The surfaces of the PES/PU composite membranes were characterized using attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, water contact angle measurement, and surface ζ-potentials. The results indicated that the membrane surfaces were assembled with hydrophilic segregation layer owing to the migration of amphiphilic PU segments during membrane preparation, which might confer the composite membranes with superior hemocompatibility. The cross-section scanning electron microscopy images of the composite membranes exhibited structure transformation from finger-like structure to sponge-like structure, which indicated that the composite membrane had tunable porosity and permeability. The further ultrafiltration experiments indicated that the composite membranes showed increased permeability and excellent antifouling ability. The blood compatibility observation indicated that PES/PU composite membranes owned decreased protein adsorption, suppressed platelet adhesion, and prolonged plasma recalcification time. These results indicated that the PES/PU composite membranes exhibited enhanced antifouling and antithrombotic properties than the pristine PES membrane. The strategy may forward the fabrication of blood compatible composite membranes for clinical blood dialysis by using the various functional miscible polymers.

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“…Thrombin adsorption on SAMs corresponds to less than 5% of the theoretical maximum for a thrombin monolayer, which was estimated to be between 271 and 301 ng cm À2 for molecules lying perpendicular or parallel to the surface [58]. This lower thrombin adsorption can be related to the non-fouling nature of the EG3 background, which can counteract the uptake of the protein of interest as described in other protein-surface systems [40,[59][60][61]. Immobilization of GGfPrt in higher concentrations did not increase thrombin adsorption since although GGfPrt-80-SAMs have six times more peptide than GGfPrt-20-SAMs, the amount of adsorbed thrombin was similar (13 ± 0.8 and 12 ± 1.1 ng cm À2 , respectively).…”

Section: Discussionmentioning

confidence: 99%

Selective albumin-binding surfaces modified with a thrombin-inhibiting peptide

Freitas¹,

Maia²,

Figueiredo³

et al. 2014

Acta Biomaterialia

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a b s t r a c tBlood-contacting medical devices have been associated with severe clinical complications, such as thrombus formation, triggered by the activation of the coagulation cascade due to the adsorption of certain plasma proteins on the surface of biomaterials. Hence, the coating of such surfaces with antithrombotic agents has been used to increase biomaterial haemocompatibility. Biomaterial-induced clotting may also be decreased by albumin adsorption from blood plasma in a selective and reversible way, since this protein is not involved in the coagulation cascade. In this context, this paper reports that the immobilization of the thrombin inhibitor D-Phe-Pro-D-Arg-D-Thr-CONH 2 (fPrt) onto nanostructured surfaces induces selective and reversible adsorption of albumin, delaying the clotting time when compared to peptide-free surfaces. fPrt, synthesized with two glycine residues attached to the N-terminus (GGfPrt), was covalently immobilized onto self-assembled monolayers (SAMs) having different ratios of carboxylate-hexa(ethylene glycol)-and tri(ethylene glycol)-terminated thiols (EG6-COOH/EG3) that were specifically designed to control GGfPrt orientation, exposure and density at the molecular level. In solution, GGfPrt was able to inactivate the enzymatic activity of thrombin and to delay plasma clotting time in a concentration-dependent way. After surface immobilization, and independently of its concentration, GGfPrt lost its selectivity to thrombin and its capacity to inhibit thrombin enzymatic activity against the chromogenic substrate n-p-tosyl-Gly-Pro-Arg-p-nitroanilide. Nevertheless, surfaces with low concentrations of GGfPrt could delay the capacity of adsorbed thrombin to cleave fibrinogen. In contrast, GGfPrt immobilized in high concentrations was found to induce the procoagulant activity of the adsorbed thrombin. However, all surfaces containing GGfPrt have a plasma clotting time similar to the negative control (empty polystyrene wells), showing resistance to coagulation, which is explained by its capacity to adsorb albumin in a selective and reversible way. This work opens new perspectives to the improvement of the haemocompatibility of blood-contacting medical devices.

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Lysine-PEG-modified polyurethane as a fibrinolytic surface: Effect of PEG chain length on protein interactions, platelet interactions and clot lysis

Cited by 107 publications

References 22 publications

Surface Modification to Control Protein/Surface Interactions

Surface Modification to Control Protein/Surface Interactions

Hemocompatible polyethersulfone/polyurethane composite membrane for high-performance antifouling and antithrombotic dialyzer

Selective albumin-binding surfaces modified with a thrombin-inhibiting peptide

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