Modified Polyurethane Surfaces Research Articles

Surface Immobilization of Oxidized Carboxymethyl Cellulose on Polyurethane for Sustained Drug Delivery.

Polyurethane (PU) has a diverse array of customized physical, chemical, mechanical, and structural characteristics, rendering it a superb option for biomedical applications. The current study involves modifying the polyurethane surface by the process of aminolysis (aminolyzed polyurethane; PU-A), followed by covalently immobilizing Carboxymethyl cellulose (CMC)polymer utilizing Schiff base chemistry. Oxidation of CMC periodically leads to the creation of dialdehyde groups along the CMC chain. When the aldehyde groups on the OCMC contact the amine group on a modified PU surface, they form an imine bond. Scanning electron microscopy (SEM), contact angle, and X-ray photoelectron spectroscopy (XPS) techniques are employed to analyze and confirm the immobilization of OCMC on aminolyzed PU film (PU-O). The OCMC gel incorporates Nitrofurantoin (NF) and immobilizes it on the PU surface (PU-ON), creating an antibacterial PU surface. The confirmation of medication incorporation is achieved using EDX analysis. The varying doses of NF have demonstrated concentration-dependent bacteriostatic and bactericidal effects on both Gram-positive and Gram-negative bacteria, in addition to sustained release. The proposed polyurethane (PU-ON) surface exhibited excellent infection resistance in in vivo testing. The material exhibited biocompatibility and is well-suited for biomedical applications.

Polyurethane surface modified with a hydrophilic polymer containing quaternary ammonium bromide

Surface with antibacterial function is important in inhibiting bacteria or biofilm formation on biomedical materials. This study reports synthesis of a quaternary ammonium bromide and N-vinylpyrrolidone-constructed antibacterial copolymer, coating it onto polyurethane surface, and evaluation of the coated surface. Antibacterial activity, surface contact angle, and protein adsorption of the coated surface were evaluated. With N-vinylpyrrolidone and quaternary ammonium bromide incorporation, the coated surface showed significantly increased hydrophilicity by exhibiting a 7 to 49% decrease in contact angle, enhanced antibacterial properties by exhibiting a 16 to 60% decrease in bacterial viability, reduced protein adsorption by demonstrating a 4 to 44% decrease in human serum albumin adsorption, and reduced bacterial adhesion by showing a 32–68% decrease in bacterial adhesion, as compared to unmodified polyurethane, as compared to unmodified polyurethane. The result indicates that the longer the substitute chain on the quaternary ammonium bromide, the higher the contact angle, the stronger the antibacterial activity, and the higher the protein adsorption as well as bacterial adhesion that the modified polyurethane surface exhibits.

Polyurethane Modified with Plasma-Ion Implantation for Medical Applications

Medical polyurethane was treated with 20 keV nitrogen ions with a fluence of 1014–1016 ions/cm2. The modified polyurethane has a layered structure consisting of a 70-nm carbonized layer and a partly depolymerized layer below the carbonized layer. The high level of activity of the polyurethane due to free radicals provides stable adhesion of protein molecules to the surface layer of the polyurethane. The high level of hydrophilicity of the modified polyurethane surface preserves the biological activity of the attached proteins. This contributes to the attachment of endothelial cells to the polyurethane surface and their proliferation. Thus, this modified polyurethane can be used as a material for soft-tissue medical implants.

Dopamine-assisted deposition of lubricating and antifouling coatings on polyurethane surfaces by one-pot ATRP and click chemistry

Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(N,N′-dimethyl-(methylmethacryloyl ethyl) ammonium propanesulfonate) (PDMAPS) were grafted on polyurethane (PU) surfaces by one-pot ATRP and click chemistry in order to improve the lubricating and antifouling properties. The successful grafting of PMPC and PDMAPS was confirmed by X-ray photoelectron spectroscopy. The immobilization of zwitterionic polymer brushes significantly improved the surface hydrophilicity and lubricating property of PU. In addition, the protein and bacteria adsorption on the modified PU surfaces were reduced greatly due to the presence of hydrated layer around the zwitterionic groups. The present surface modification approach was simple and versatile for functionalization of polymer surfaces.

Characterization of active screen plasma modified polyurethane surfaces

In order to improve the surface properties of polyurethane (PU), samples of polyurethane have been surface modified using a newly developed active screen plasma modification (ASPM) technique. The change in the surface topography was investigated by profilometry, atomic force microscopy (AFM) and scanning electron microscopy (SEM); the chemical composition and bonding structure of the plasma modified PU surface were characterized by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR); and the wettability of the modified surface was studied by contact angle and surface energy was calculated. The results show that the ASPM technique not only can effectively alter the surface topography of polyurethane from a closed cell structure to porous open structure but also result in transformation of ester groups into new OH groups in the top surface layer. The changes of surface topography, structure and chemical composition by plasma treatment have also effectively modified the wettability of the polyurethane surface.

Lysine–poly(2-hydroxyethyl methacrylate) modified polyurethane surface with high lysine density and fibrinolytic activity

We have developed a potentially fibrinolytic surface in which a bioinert polymer is used as a spacer to immobilize lysine such that the ε-amino group is free to capture plasminogen when in contact with blood. Adsorbed plasminogen can be activated to plasmin and potentially dissolve nascent clots formed on the surface. In previous work lysine was immobilized through a poly(ethylene glycol) (PEG) spacer; however, the graft density of PEG was limited and the resulting adsorbed quantity of plasminogen was insufficient to dissolve clots efficiently. The aim of the present work was to optimize the surface using graft-polymerized poly(2-hydroxyethyl methacrylate) (poly(HEMA)) as a spacer to increase the grafting density of lysine. Such a poly(HEMA)–lysine modified polyurethane (PU) surface is expected to have increased plasminogen binding capacity and clot lysing efficiency compared with PEG–lysine modified PU. A lysine density of 2.81nmolcm−2 was measured on the PU–poly(HEMA)–Lys surface vs. 0.76nmolcm−2 on a comparable PU–PEG–Lys surface reported previously. The poly(HEMA)–lysine-modified surface was shown to reduce non-specific (fibrinogen) adsorption while binding plasminogen from plasma with high affinity. With increased plasminogen binding capacity these surfaces showed more rapid clot lysis (20min) in a standard in vitro assay than the corresponding PEG–lysine system (40min). The data suggest that poly(HEMA) is superior to PEG when used as a spacer in the immobilization of bioactive molecules at high density. This method of modification may also provide a generic approach for preparing bioactive PU surfaces of high activity and low non-specific adsorption of proteins.

CD34 monoclonal antibody-immobilized electrospun polyurethane for the endothelialization of vascular grafts

Targeting endothelial progenitor cells (EPC) for in vivo endothelialization is an emerging and promising approach for the development of cardiovascular medical devices. This study examined the efficacy of capturing CD34 positive EPC onto polyurethane (PU) immobilized with CD34 monoclonal antibodies (mAbs) (a biomecial polymer for cardiovascular devices). Electrospun PU matrices were fabricated and heparin was immobilized along with CD34 mAb. The modified PU surfaces at each step were characterized by contact angle measurements, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). XPS showed that each surface was modified, as expected in terms of the chemical composition. The amine-terminated poly(ethylene glycol)(PEG)-PU surface was considerably more hydrophilic than the PU surface. In addition, its surface roughness was similar to the PU surface, indicating that PEG was sufficiently and evenly grafted onto the PU surface. The CD34 mAb-immobilized PEG-PU surface was less hydrophilic than PEG-PU and extremely rough as compared to the other two surfaces. These results demonstrate that relatively large CD34 mAbs were immobilized on the PU surface. The surface density of the immobilized CD34 mAb, which was quantified using an enzyme-linked immune-sorbent assay (ELISA), was increased to ∼40 ng/cm2 by varying the feed amount up to ∼200 ng/cm2 and co-immobilizing with heparin. These results suggest that the co-immobilization with heparin can provide two benefits: inhibiting initial occlusion and improving the surface density of CD34 mAb. The in vitro cell study also demonstrated that the CD34 mAb-immobilized PU surface was favorable for cell attachment and proliferation. Therefore, in this study, a novel approach was developed to achieve endothelialization for cardiovascular applications by immobilizing CD34 onto PU, and the synergistic effects of co-immobilization with heparin on the bioactivity of the PU surfaces was demonstrated.

Fabrication of endothelial cell-specific polyurethane surfaces co-immobilized with GRGDS and YIGSR peptides

Polyurethane (PU) is widely used as a cardiovascular biomaterial due to its good mechanical properties and hemocompatibility, but it is not adhesive to endothelial cells (ECs). Cell adhesive peptides, GRGDS and YIGSR, were found to promote adhesion and spreading of ECs and showed a synergistic effect when both of them were used. In this study, a surface modification was designed to fabricate an EC-active PU surface capable of promoting endothelialization using the peptides and poly(ethylene glycol) (PEG) spacer, The modified PU surfaces were characterizedin vitro. The density of the grafted PEG on the PU surface was measured by acid-base back titration to the terminal-free isocyanate groups. The successful immobilization of peptides was confirmed by amino acid analysis, following hydrolysis, and contact angle measurement. The uniform distribution of peptides on the surface was observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). To evaluate the EC adhesive property, cell viability test using human umbilical vein EC (HUVEC) was investigatedin vitro and enhanced endothelialization was characterized by the introduction of cell adhesive peptides, GRGDS and YIGSR, and PEG spacer. Therefore, GRGDS and YIGSR co-immobilized PU surfaces can be applied to an EC-specific vascular graft with long-term patency by endothelialization.

Protein-resistant polyurethane prepared by surface-initiated atom transfer radical graft polymerization (ATRgP) of water-soluble polymers: Effects of main chain and side chain lengths of grafts

Water-soluble poly(oligo(ethylene glycol) methacrylate) (poly(OEGMA)) with various main chain and side chain lengths were grafted to polyurethane (PU) surface by surface-initiated atom transfer radical graft polymerization (s-ATRgP). The polymer main chain length was varied by varying the molar ratio of monomer to free initiator in solution (typically 5:1, 50:1, 100:1). Three different side chain lengths were obtained using different OEGMA monomers (MW 300, 475, 1100 g/mol). Water contact angle and X-ray photoelectron spectroscopy (XPS) were used to characterize the modified PU surfaces. The respective effects of poly(OEGMA) main chain and side chain lengths on fibrinogen (Fg) and lysozyme (Lys) adsorption were investigated in single protein systems at room temperature in TBS, pH 7.4. The poly(OEGMA)-grafted PU surfaces were found to be highly protein-resistant, with reductions of Fg and Lys adsorption in the range of 84–98% and 67–91%, respectively, compared to the unmodified PU surface. The adsorption of both proteins decreased with increasing poly(OEGMA) main chain length for a given side chain length (number of EO units). For a given main chain length, the Fg adsorption level did not change significantly with increasing side chain length. However, Lys adsorption increased with increasing side chain length, possibly due to decreasing graft density as monomer size and footprint on the surface increase. Adsorption resistance was generally greater for the bigger protein.

Biomembrane mimetic polymer poly (2‐methacryloyloxyethyl phosphorylcholine‐co‐n‐butyl methacrylate) at the interface of polyurethane surfaces

Polyurethane (PU) is widely used to make artificial heart and blood vessel wells; however, its thrombogenicity in vivo is still in question. The biomembrane-mimetic and water-soluble polymers, poly (2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB), were used to modify polyurethane (PU) surfaces for improving their hemocompatibility. The morphologies of the PMB modified PU surfaces were examined by using atomic force microscopy and the parameters of the PMB absorption kinetics were extracted from dynamic water contact angle measurements. Two-phase domains, the hard and soft segment phases, were observed on the PU surfaces under the aqueous conditions. The absorbed PMB molecules formed the isolated layers first on the hydrophobic hard segments, and subsequently networked as the PMB concentration increased. The increments of PMB concentration led to the decrement of the effective molar activation (wetting) free energy DeltaG.

200. Cholesterol Modified Polyurethane as a Matrix for Cell Based Cardiovascular Therapy Using Blood Outgrowth Endothelial Cells (BOEC): Potential for Lentivirus Mediated Gene Therapy

Polyurethane is a durable elastomer capable of serving as a gene delivery platform in the cardiovascular system. Precoating polyurethane cardiovascular devices with a layer of autologous endothelial cells would hypothetically protect the device from thrombus formation. However, biocompatibility issues often hinder attempts to seed vascular devices with endothelial cells. In these studies, blood outgrowth endothelial cells (BOEC's) were used to test the hypothesis that covalent attachment of cholesterol to the polyurethane amide group would create a high affinity surface for attachment and adhesion of autologous BOEC's, prior to implantation as cardiovascular devices. Cholesterol was covalently appended to the polyether polyurethane Tecothane, by activating polyurethane nitrogens and attaching a bromo-alkyl side chain. Expanded ovine BOEC's were cultured on the modified polyurethane to compare viability and cell retention under vascular flow conditions. BOEC susceptibility to lentivirus mediated ectopic gene expression was also analyzed, using a VSV-g pseudotyped, self-inactivating lentivirus with an internal CMV promoter driving an eGFP gene, in conjunction with growth on cholesterol modified polyurethane. Cell adhesion was investigated with BOEC's cultivated until confluence on Tecothane ± appended cholesterol, exposed to physiological shear stress (25 dynes/cm2) for two hours. BOEC's growing on cholesterol modified polyurethane retained 94.1 ± 0.36 % of cells. In contrast cells cultured on unmodified polyurethane retained only 4.56 ± 0.85 % (p = 0.02, n = 3) of the initial cells. Green fluorescent protein (GFP) encoding lentivirus (MOI = 250) vectors transduced 100% of cultured BOEC's. GFP expression was observed in all subcultured BOEC's beyond four cell passages strongly suggesting permanent ectopic gene incorporation. GFP expressing BOEC's continued to grow and express GFP on cholesterol modified polyurethane surfaces. In conclusion, cholesterol modified polyurethane seeded with BOEC's represent a formulation with great potential for intravascular cell based therapies.

Interaction of fibrinogen with surfaces of end-group-modified polyurethanes: a surface-specific sum-frequency-generation vibrational spectroscopy study.

Fibrinogen adsorption on polyurethanes with different surface-modifying end groups (SMEs) has been studied with sum-frequency-generation vibrational spectroscopy (SFG). The results show very different protein adsorption properties for different SMEs on the same backbone polymer. Fibrinogen binds weakly on the hydrophilic backbone of a poly(dimethyl siloxane) (PDMS)-modified polyurethane surface but leaves the hydrophobic PDMS part untouched. On sulfonate end-group-modified (SO(3(-) )) polyurethane surfaces, fibrinogen adsorbs well. However, on poly(ethylene oxide) (PEO)-modified surfaces, it adsorbs poorly. The protein-resistant character of PEO is probably due to steric repulsion. This work demonstrates the utility of SFG in the study of protein adsorption on polymeric biomaterials at the molecular level and the ability of SMEs to mediate protein adsorption.

Photochemical grafting of α-propylsulphate-poly(ethylene oxide) on polyurethane surfaces and enhanced antithrombogenic potential

The aim of this study is the grafting of photoreactive α-propylsulphate-poly(ethylene oxide) (PEO-SO 3), one end of which is capped with an azidophenyl group, on polyurethane (PU) surfaces via a photochemical technique. The anti-Factor Xa activity and the platelet adhesion characteristics of the modified PU surface were evaluated by a chromogenic assay method and by a flow-controlled chamber method, respectively. X-ray photoelectron spectroscopy analysis showed that PEO-SO 3 was covalently grafted on the PU surface. The grafted surface showed anti-Factor Xa activity in the presence of antithrombin III, and significantly reduced platelet adhesion characteristics as compared with those of the unmodified PU surface. These results suggest that the grafting of PEO-SO 3 improves the antithrombogenicity of PU surfaces.

Synthesis of a new photoreactive derivative of dipyridamole and its use in the manufacture of artificial surfaces with low thrombogenicity.

Photoimmobilization of dipyridamole (Persantin) was accomplished through the use of a new synthetic conjugate molecule, 1. Persantin is a powerful inhibitor of platelet activation and aggregation and is widely used as a vasodilator. Conjugate 1 consists of triply protected dipyridamole [three of the four hydroxyl groups carry a tert-butyldimethylsilyl (TBDMS) protective group) and the photoreactive 4-azidobenzoyl group. A short hydrophilic spacer chain, derived from triethylene glycol, separates the protected dipyridamole system and the photoreactive group. Compound 1 was immobilized on polyurethane sheets (Pellethane D-55) through irradiation with ultraviolet (UV) light, and the protective groups were removed afterward. The resulting modified polyurethane surfaces were characterized by different physicochemical techniques: UV extinction, contact angle measurements (captive bubble technique), and X-ray photoelectron spectroscopy (XPS). The UV extinction measurements showed the presence of 13 +/- 1 nmol of immobilized dipyridamole/cm2. The contact angle measurements revealed that the modified surface was markedly more hydrophilic than the control (i.e. unmodified polyurethane). XPS measurements clearly established the presence of immobilized dipyridamole in the outermost layers of the modified surface. This was especially clear from the XPS spectra recorded at a low take-off angle (approximately 6 degrees). Furthermore, the XPS spectra showed that the TBDMS protective groups had been quantitatively removed during the deprotection/washing treatment. The in vitro blood compatibility of the modified surface was studied with the thrombin generation assay as developed in our group, as well as with scanning electron microscopy. The thrombin generation test produced a lag time of 1275 s for the modified surface, as opposed to 569 s for the control. Scanning electron microscopy showed that far fewer platelets adhere to the modified surface (approximately 7 x 10(3)/mm2) as compared to the control (approximately 6 x 10(2)/mm2). Taken together, the experimental data reveal that the modified surface has excellent blood compatibility in vitro. It is discussed that the use of conjugate 1 leads to simultaneous exposure of dipyridamole at the modified surface and to a marked increase of the surface hydrophilicity, which is likely to hamper adsorption of plasma proteins. The combination of these effects is uniquely related to the molecular buildup of 1. Conjugate 1 will be used in future work that is aimed at preparing small-caliber polyurethane vascular grafts with a blood compatible lumenal surface.

In vitro leukocyte adhesion to modified polyurethane surfaces: III. Effect of flow, fluid medium, and platelets on PMN adhesion

The operation of filters used to remove leukocytes from red cell concentrates may depend on the adhesion and mechanical trapping of leukocytes. If adhesion is a major component of filtration then filter materials which augment leukocyte adhesion will be useful. In previous leukocyte adhesion studies, done without flow, poly(ethyleneimene) (PEI) modified polyurethane (PU) films were shown to have greater adhesion when compared with unmodified PU. Since filtration is done under flow conditions, it was decided to study PMN adhesion at a number of flow rates using an established parallel plate flow cell. The influence of divalent cations, plasma and platelets were investigated in the presence of red cells, 40% Hematocrit. The number of adherent PMNs to the PEI modified films was always substantially higher than that for the unmodified ones when the shear rate was set at 30 s-1. When using Tyrode's solution containing albumin, with or without divalent cations, a maximum in PMN adhesion was found between the shear rates of 10 and 100 s-1. With Tyrode's solution containing albumin and with 10% (v/v) plasma in saline, the addition of platelets increased PMN adhesion when divalent cations were absent. Adhesion levels with 10% (v/v) plasma in saline were reduced when compared to Tyrode's solution containing albumin without divalent cations. These results support the use of filtration conditions where the concentration of plasma is reduced and the concentration of divalent cations is increased. Detailed evaluation of filter function with flow rate is also recommended. A cell adhesion promoting polymer coating, such as PEI, may be useful in improving filter efficiency.