Bulk, surface and blood-contacting properties of polyether polyurethanes modified with polydimethylsiloxane macroglycols

The bulk, surface and blood-contacting properties of a series of polyether polyurethanes, modified with three different polydimethylsiloxane (PDMS) macroglycol segments, were evaluated. The PDMS oligomers were terminated with hydroxy-tipped end groups of varying polarity. The effect of substituting the polytetramethylene oxide (PTMO) soft segment of a base polyurethane with 5 and 15 wt% of these PDMS-containing polyols was investigated. The ultimate tensile strength and elongation at break appeared to be the bulk properties most significantly affected by the addition of the PDMS-containing polyols. Underwater contact angle data indicate that the block copolymer surface became more hydrophilic with increasing PDMS content. In a vacuum, as determined from the ESCA data, the relatively non-polar PDMS soft segments preferentially oriented at the surface with increasing PDMS incorporation. Despite the variation in the surface properties, the blood compatibility of these polymers was not significantly affected by the addition of the PDMS-containing polyols.     

Biological responses to polyethylene oxide modified polyethylene terephthalate surfaces.

Polyethylene oxide (PEO) of molecular weights 5,000, 10,000, 18,500, and 100,000 g/mol was covalently grafted to surfaces of otherwise cell adhesive polyethylene terephthalate (PET) films. Analysis of these surfaces by measurement of contact angles and ESCA verified the presence of the grafted PEO. Protein adsorption assays of radiolabeled albumin and fibrinogen showed a marked reduction in adsorbed protein for the 18,500 and 100,000 molecular weight PEO coupled surfaces. Cell growth assays using human foreskin fibroblasts in culture showed that the higher-molecular-weight PEO surfaces supported cell growth to a much lower extent than the two lower-molecular-weight PEOs. Flow of whole blood over these surfaces and visualization of platelet adherence using epifluorescence video-microscopy showed very low platelet adherence only on the two higher-molecular-weight PEO coupled surfaces. Scanning electron microscopy corroborated these results. It was concluded that PEO of molecular weights neighboring 18,500 and higher was effective in reducing protein adsorption and cellular interactions on these surfaces.     

Ex vivo interactions and surface property relationships of polyetherurethanes

Despite the use of polyurethanes in a number of blood-contacting applications, little is known about the contributing effects of the various polyurethane components in thrombogenesis. In order to investigate blood-polyurethane interactions, a number of different polyurethanes were examined in an acute canine ex vivo series shunt experiment. Multiprobe surface characterization techniques, including contact angle measurements, ESCA, ATR-IR, and SEM were used to obtain surface property information on the materials studied. The polyurethanes examined included several with different soft segment types, a series of materials with different hard segment diisocyanates and chain extenders, a series consisting of the same polymer cast from different solvents, a zwitterionomer, and a hard segment analog. Two commercial urethanes were also examined, and the effect of methanol extraction on these materials was studied. The blood-contact and surface characterization results indicated that both the surface concentration and type of hard segment were of importance in determining blood response. The relative concentration of hard segment on the polymer surface was found to affect the observed blood-material interaction, although the extent of this effect was found to depend on the hard and soft segment components of the copolymer system. Both the surface properties and thrombogenicity of a particular polyurethane were changed by casting from different solvents, indicating the need to optimize and control fabrication conditions. Methanol extraction was found to improve the thromboresistance of the commercial polyurethanes.     

Biostability and blood-contacting properties of sulfonate grafted polyurethane and Biomer

Sulfonate-containing polyurethanes were evaluated for in vivo biodegradation using subcutaneously implanted tensile bars. In addition, these anionically charged polyurethanes were evaluated for in vivo activation of human complement C3a and ex vivo platelet deposition in arteriovenouslyshunted canines. The sulfonate derivatized polymers included laboratory synthesized polyurethane and Biomer. Other polymers used for references included Intramedic^TM polyethylene, Silastic^TM and a poly(ethylene oxide) based polyurethane. The biodegradation results indicated that Biomer and the laboratory sulfonated Biomer (both manufactured with stabilizers), remained mechanically stable, retaining both tensile strength and elasticity after 4 weeks of subcutaneous implantation. The unstabilized polyurethanes (with or without sulfonation), however, showed marked cracking and a loss of mechanical properties after the same period of subcutaneous implantation. Sulfonated polyurethanes depressed human complement C3a activation in plasma, as indicated by decreased levels of anaphylatoxin production. The results of canine ex vivo blood contacting experiments were conducted in both an acute and chronic model and demonstrated decreased platelet deposition and activation for the sulfonated polyurethanes.     

In vitro study of blood-contacting properties and effect on bacterial adhesion of a polymeric surface with immobilized heparin and sulphated hyaluronic acid

The blood-contacting properties and the effect on bacterial adhesion of a material based on polyurethane and poly(amido-amine) (PUPA), both in its native form and with the anticoagulant molecules heparin or sulphated hyaluronic acid (HyalS3.5) electrostatically bonded to its surface, were evaluated and compared in vitro. The presence of the biological molecules on the surface was revealed by a dye test and ATR/FTIR analysis. Bound heparin was found to maintain its physiological action, in terms of thrombin inactivation, as well as did free heparin. Moreover, it reduced the degree of platelet adhesion. On the contrary, bound HyalS3.5 lost its anticoagulant activity, though it reduced platelet adhesion. The number of platelets on both modified surfaces was low. Their shape distribution, as determined by SEM, did not differ significantly on the two modified surfaces or with respect to the bare PUPA surface. HyalS3.5 and heparin also inhibited adhesion of Staphylococcus epidermidis to the material. A possible relationship between the platelet and bacterial adhesion is ascribed to the mediating role of plasma proteins.     

In vitro study of blood-contacting properties and effect on bacterial adhesion of a polymeric surface with immobilized heparin and sulphated hyaluronic acid

The blood-contacting properties and the effect on bacterial adhesion of a material based on polyurethane and poly(amido-amine) (PUPA), both in its native form and with the anticoagulant molecules heparin or sulphated hyaluronic acid (HyalS3.5) electrostatically bonded to its surface, were evaluated and compared in vitro. The presence of the biological molecules on the surface was revealed by a dye test and ATR/FTIR analysis. Bound heparin was found to maintain its physiological action, in terms of thrombin inactivation, as well as did free heparin. Moreover, it reduced the degree of platelet adhesion. On the contrary, bound HyalS3.5 lost its anticoagulant activity, though it reduced platelet adhesion. The number of platelets on both modified surfaces was low. Their shape distribution, as determined by SEM, did not differ significantly on the two modified surfaces or with respect to the bare PUPA surface. HyalS3.5 and heparin also inhibited adhesion of Staphylococcus epidermidis to the material. A possible relationship between the platelet and bacterial adhesion is ascribed to the mediating role of plasma proteins.     

Biostability and blood-contacting properties of sulfonate grafted polyurethane and Biomer.

Sulfonate-containing polyurethanes were evaluated for in vivo biodegradation using subcutaneously implanted tensile bars. In addition, these anionically charged polyurethanes were evaluated for in vivo activation of human complement C3a and ex vivo platelet deposition in arteriovenously-shunted canines. The sulfonate derivatized polymers included laboratory synthesized polyurethane and Biomer. Other polymers used for references included Intramedic polyethylene, Silastic and a poly(ethylene oxide) based polyurethane. The biodegradation results indicated that Biomer and the laboratory sulfonated Biomer (both manufactured with stabilizers), remained mechanically stable, retaining both tensile strength and elasticity after 4 weeks of subcutaneous implantation. The unstabilized polyurethanes (with or without sulfonation), however, showed marked cracking and a loss of mechanical properties after the same period of subcutaneous implantation. Sulfonated polyurethanes depressed human complement C3a activation in plasma, as indicated by decreased levels of anaphylatoxin production. The results of canine ex vivo blood contacting experiments were conducted in both an acute and chronic model and demonstrated decreased platelet deposition and activation for the sulfonated polyurethanes.     

Antibacterial activity of zinc modified titanium oxide surface

Titanium-based implants are successfully used for various biomedical applications. However, in some cases, e.g. in dental implants, failures due to bacterial colonization are reported. Surface modification is a commonly proposed strategy to prevent infections. In this work, titanium oxide, naturally occurring on the surface of titanium, was modified by promoting the formation of a mixed titanium and zinc oxide, on the basis of the idea that zinc oxide on titanium surface may act as the zinc oxide used in pharmaceutical formulation for its lenitive and antibacterial effects. The present work shows that it is possible to form a mixed titanium and zinc oxide on titanium surfaces, as shown by Scanning Electron Microscopy and XPS analysis. To this end titanium was preactivated by UV on crystalline titanium oxide, both in the anatase form or in the co-presence of anatase and rutile. By performing antibacterial assays, we provide evidence of a significant reduction in the viability of five streptococcal oral strains on titanium oxide surfaces modified with zinc. In conclusion, this type of chemical modification of titanium oxide surfaces with zinc might be considered a new way to reduce the risk of bacterial colonization, increasing the lifetime of dental system applications.     

Synthesis and nonthrombogenicity of fluoroalkyl polyetherurethanes

New polyetherurethanes carrying fluoroalkyl substituents in the side chains were synthesized from N,N-di(hydroxyethyl)heptadecafluorooctyl-sulfonamide (a chain extender), 4,4'-disocyanatodiphenylmethane, and poly(tetramethylene glycol). Various kinds of polyetherurethanes having different tensile properties were prepared by changing the content of fluoroalkyl chain extender or the molecular weight of poly(tetramethylene glycol). The surface of a film made from the fluoroalkyl polyetherurethane was strongly water-repulsive. The in vitro thrombus formation on the fluoroalkyl polyetherurethanes was reduced by increasing the content of chain extender for the same molecular weight of poly(tetramethylene glycol). Protein adsorption, platelet adhesion, and platelet activation on the fluoroalkyl polyetherurethanes were also investigated.     

Surface modification with polyethylene glycol-corn trypsin inhibitor conjugate to inhibit the contact factor pathway on blood-contacting surfaces

Blood contacting surfaces bind plasma proteins and trigger coagulation by activating factor XII (FXII). The objective of this work was to develop blood contacting surfaces having the dual properties of protein resistance and inhibition of coagulation. Gold was used as a model substrate because it is amenable to facile modification using gold-thiol chemistry and to detailed surface characterization. The gold was modified with both polyethylene glycol (PEG) and corn trypsin inhibitor (CTI), a potent and specific inhibitor of activated FXII (FXIIa). Two methods of surface modification were developed; sequential and direct. In the sequential method PEG was first chemisorbed on gold; CTI was then attached to the PEG. In the direct method a conjugate of PEG and CTI was first prepared; the conjugate was then immobilized on gold. The surfaces were characterized by water contact angle and XPS. Biointeractions with the modified surfaces were assessed by measuring fibrinogen adsorption from buffer and plasma and by immunoblot analysis of eluted proteins after plasma exposure. Inhibition of FXIIa, autoactivation of FXII, and clotting times of plasma in contact with the surfaces were also measured. Both the sequential and direct surfaces showed reduced protein adsorption, increased FXIIa inhibition and longer clotting times compared with controls. Although the CTI density was lower on surfaces prepared using the sequential method, surfaces so prepared exhibited greater CTI activity than those generated by the direct method. It is concluded that the activity of immobilized PEG-CTI depends on the method of attachment and that immobilized CTI may be useful in rendering biomaterials more blood compatible.     

The efficacy of an acrylic intraocular lens surface modified with polyethylene glycol in posterior capsular opacification

To investigate if the surface modification of intraocular lens (IOL) is efficient in the prevention of posterior capsular opacification (PCO), the acrylic surface of intraocular lens (Acrysof) was polymerized with polyethylene glycol (PEG-IOL). The human lens epithelial cells (1 x 10(4) cells/mL) were inoculated on PEG grafted or unmodified acrylic lenses for the control. The adherent cells on each IOL surface were trypsinized and counted. The every PEG-IOL was implanted in 20 New Zealand rabbits after removal of crystalline lens. The formations of PCO were checked serially through retroilluminated digital photography, and the severity scores were calculated using POCOman. The cell adherence patterns on each IOL were examined by scanning electron microscopy. As a result, the mean number of adherent cells of PEG-IOL (3.2+/-1.1 x 10(3)) tended to be smaller than that of the acrylic controls (3.6+/-1.9 x 10(3)) without a statistical significance (p=0.73). However, the mean severity of PCO formation in PEG-IOL was significantly lower than that in the control during the third to sixth weeks after surgery. Scanning electron microscopy revealed that the more patch-like cells were found firmly attached to the IOL surface in control than in the PEG-IOL. Conclusively, PEG polymerization to the acrylic IOL would possibly lessen the formation of PCO after cataract removal.     

Hybrid polycaprolactone/polyethylene oxide scaffolds with tunable fiber surface morphology,improved hydrophilicity and biodegradability for bone tissue engineering applications

In the present study, we attempt to modify Polycaprolactone (PCL) by blending it with a water soluble polymer Polyethyleneoxide (PEO) having two different molecular weights (Mv ~1,00,000 and 6,00,000) using electrospinning technique. The effect of PEO molecular weight and blend ratio on fiber morphology, porosity, surface wettability, static and dynamic mechanical properties of PCL was investigated. In vitro degradation studies in phosphate buffer saline (PBS) at 37 °C demonstrated formation of pores on fiber surface especially in blend scaffolds with 50:50 ratios. In vitro studies using human osteoblast sarcoma (hOS) cell lines on blend scaffolds showed improved cellular response with good cell adhesion, viability and proliferation. The study revealed that incorporation of PEO on PCL scaffolds complemented the properties of PCL and facilitated fabrication of scaffolds with improved hydrophilicity, mechanical property and tunable degradation profile with better cell viability which makes it an ideal candidate for bone tissue engineering applications.     

Segmented polyurethane modified by photopolymerization and cross-linking with 2-methacryloyloxyethyl phosphorylcholine polymer for blood-contacting surfaces of ventricular assist devices

To improve the biocompatibility of pulsatile ventricular assist devices (VADs), the blood-contacting surface of the segmented polyurethane (SPU) diaphragm employed in an electromechanical VAD was modified by introducing 2-methacryloyloxyethyl phosphorylcholine (MPC) units into its surface and forming an interpenetrating polymer network (IPN) structure, which contained independently cross-linked MPC polymer and SPU. The SPU diaphragm modified with an IPN structure was then assembled into a target test pump and underwent continuous pump operation at 37°C for 2 weeks in a simulated systemic circulation using a mock circulatory loop. The surface characteristics of the pump diaphragm after 2 weeks of pump operation were then analyzed with an X-ray photoelectron spectroscope (XPS) and gold-colloid-labeled immunoassay. The XPS surface analysis of the IPN-modified SPU indicated the firm anchoring of MPC units even after 2 weeks of pump operation (the phosphor : carbon ratio was reduced by only 0.09%). The IPN-modified diaphragm prevented protein adsorption as well as cell adhesion in comparison to the unmodified SPU surface. This result thus validated that (1) the IPN structure could firmly secure MPC units to the SPU surface even in a high-mechanical-stress and high-shear environment, (2) the antithrombogenic power of MPC units remained unchanged after 2 weeks of continuous exposure to a high-shear environment, and (3) the IPN modified SPU cross-linked with MPC could be a powerful antithrombogenic surface for blood pumps used for chronic circulatory support of cardiac patients.     

Poly(DL-lactic acid) film surface modification with heparin for improving hemocompatibility of blood-contacting bioresorbable devices

This work describes a simple method to immobilize heparin by covalent bonding to the surface of poly(lactic acid) film with the aim of showing improved hemocompatibility. Carboxyl groups present in heparin molecules were activated by reaction with N-hydroxy-succinimide and allowed to react with free amino groups created at the surface of poly(DL-lactic acid) films by controlled aminolysis. Contact angle measurements and XPS analysis confirmed the binding. Quantification was determined by radioactivity using heparin labeled with tritium. The surface exhibited anti factor Xa activity, thus confirming the presence of bounded heparin that kept some biological activity. Finally platelets adhesion showed less platelet adhesion on heparin modified films as well as preserved morphology.     

Properties of extruded poly(tetramethylene oxide)-polyurethane block copolymers for blood-contacting applications

The bulk and surface properties and blood compatibility of a series of polyurethanes based on methylene bis(p-phenyl isocyanate), 1,4-butanediol, and poly(tetramethylene oxide) of molecular weight 1000 were studied. The hard-to-soft segment ratio of these multiphase polymers was varied, and the effect of substituting a poly(dimethylsiloxane)-containing polyol in place of 5% of the polyether soft segment was studied. Bulk properties such as tensile strength and modulus increased with hard segment content, as did surface wettability and ESCA nitrogen content. However, blood compatibility measured by a canine ex vivo blood-contacting experiment was not found to vary with hard/soft segment ratio. The addition of the silicone-containing polyol did not significantly lower the surface wettability, although ESCA-measured silicon content increased and physical properties were unfavourably affected by the incorporation of this co-soft segment. Incorporation of the siloxane-containing component resulted in increased platelet adhesion and fibrinogen deposition at most blood contact times in comparison with the other polyurethanes.     

表面修饰煅烧骨的制备及其理化性质的研究

探讨一种新的仿生骨材料表面修饰煅烧牛松质骨的制备方法,以提高煅烧牛松质骨作为组织工程骨的活性。将制备好的大小一致的煅烧牛松质骨随机分成两组,分别浸泡在配制好的单倍模拟体液(SBF)和1.5倍SBF中。每组材料的浸泡时间均为7、14和21d共3个时间点。浸泡结束干燥后用扫描电镜(SEM)观察材料表面形态并分析材料表面矿化成分。通过比较筛选出效果最理想的表面修饰煅烧牛松质骨材料,研究其孔径、孔隙率、抗压和抗折强度等理化性质,并与未经表面修饰的煅烧骨材料进行比较。研究表明,煅烧骨材料在1.5倍SBF中浸泡14d可以获得最佳表面修饰效果,同时保留了原有煅烧骨材料的基本理化特性。     

Polymers incorporating nitric oxide releasing/generating substances for improved biocompatibility of blood-contacting medical devices

The current state-of-the-art with respect to the preparation, characterization and biomedical applications of novel nitric oxide (NO) releasing or generating polymeric materials is reviewed. Such materials show exceptional promise as coatings to prepare a new generation of medical devices with superior biocompatiblity. Nitric oxide is a well-known inhibitor of platelet adhesion and activation, as well as a potent inhibitor of smooth muscle cell proliferation. Hence, polymers that release or generate NO locally at their surface exhibit greatly enhanced thromboresistivity and have the potential to reduce neointimal hyperplasia caused by device damage to blood vessel walls. In this review, the use of diazeniumdiolates and nitrosothiols as NO donors within a variety polymeric matrixes are summarized. Such species can either be doped as discrete NO donors within polymeric films, or covalently linked to polymer backbones and/or inorganic polymeric filler particles that are often employed to enhance the strength of biomedical polymers (e.g., fumed silica or titanium dioxide). In addition, very recent efforts to create catalytic polymers possessing immobilized Cu(II) sites capable of generating NO from endogenous oxidized forms of NO already present in blood and other physiological fluids (nitrite and nitrosothiols) are discussed. Preliminary literature data illustrating the efficacy of the various NO release/generating polymers as coatings for intravascular sensors, extracorporeal blood loop circuits, and arteriovenous grafts/shunts are reviewed.     

Vacuum ultraviolet treatment of polyethylene to change surface properties and characteristics of protein adsorption

The purpose of this study was to investigate the mineralization leading to osseointegration of strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement injected into cancellous bone in vivo. Sr-HA cement was injected into the ilium of rabbits for 1, 3, and 6 months. The bone mineralization area was found to be largest at 3 months, then at 1 month, and smallest at 6 months (p < 0.01) measured with tetracycline labeling. Osseointegration of Sr-HA cement was achieved at 3 months as observed by scanning electron microscopy. A high calcium and phosphorus area was observed at the interface of bone-Sr-HA cement determined by energy-dispersive X-ray analysis. Transmission electron microscopy gave evidence of the mechanism of bone formation. Dissolution of Sr-HA into debris by the bone remodeling process was thought to increase the concentration of calcium and phosphorus at the interface of bone-Sr-HA cement and stimulate bone formation. Crystalline Sr-HA formed an amorphous layer and dissolved into the surrounding solution, then apatite crystallites were precipitated and formed new bone at 3 months. This young bone then becomes mature bone, which bonds tightly to the Sr-HA cement with collagen fibers inserted perpendicularly after 6 months.     

In vivo biostability of polyether polyurethanes with fluoropolymer and polyethylene oxide surface modifying endgroups; resistance to metal ion oxidation

Polyether polyurethanes are subject to oxidation catalyzed by, and through direct (redox) reaction with transition metal ions (metal ion oxidation, MIO). The source of the ions is corrosion of metallic parts within an implanted device. A Shore 80A polyether polyurethane was modified with fluoropolymer (E80AF) or polyethylene oxide (E80AP) surface modifying end groups (SME). The SME migrates to the surface to form a covalently bonded monolayer, while maintaining the bulk properties of the polyurethane. In vitro tests in H(2)O(2) solution indicated that both SME's accelerated MIO. Tubing samples containing cobalt mandrels were implanted in the subcutis of rabbits for up to 2 years. In vivo, E80AF significantly slowed the rate of visible degradation, but did not prevent MIO. E80AP had virtually identical visual performance to the unmodified control in vivo. Infrared spectroscopy and molecular weight correlated well with visual appearance. When cracks were seen, polyether soft segment oxidation was occurring. Both E80AP and the control developed severe loss of molecular weight in vivo. The changes were much less severe for E80AF. Thus, contrary to in vitro test results, the PEO SME had no effect at all on MIO resistance, while the fluoropolymer SME produced a significant improvement in biostability.     

Physical and blood-contacting properties of polyurethanes based on a sulfonic acid-containing diol chain extender.

Polyurethanes chain extended with N,N-bis (2-hydroxyethyl)-2-aminoethane-sulfonic acid (BES) were synthesized. The effect of the sulfonic acid group on the polymers' bulk, surface, and blood-contacting properties was evaluated by comparing the BES-based polymers with polyurethanes based on N-ethyldiethanolamine (EDEA). In addition, the effect of soft-segment polarity was addressed by comparing polyurethanes based on polytetramethylene oxide (PTMO) (MW = 1000) with polymers based on polyethylene oxide (PEO) (MW = 1000). The EDEA control samples had physical properties similar to a viscous fluid. The presence of the sulfonic acid group dramatically enhanced the degree of microphase separation and the mechanical strength of all the polymers. The more polar PEO soft segment resulted in polymers which were more phase mixed than the PTMO-based polyurethanes. Surface characterization studies revealed that in vacuum, all the surfaces were enriched in the polyether soft-segment phase. After 24-h equilibration in water, all the surfaces had similar surface polarities independent of the SO3H content. The canine ex vivo blood-contacting results showed that the sulfonic acid group in the PTMO-based polymers significantly reduced the number and activation of the adherent platelets. Fibrinogen deposition, however, increased with increasing sulfonic acid content. In contrast, platelet and fibrinogen deposition on the sulfonic acid-containing PEO-based polymers was greatly enhanced.