Evaluation of antithrombogenic thermodilution catheter

In order to prevent the complications accompanied with pulmonary-artery (Swan-Ganz) catheterization, we have developed an antithrombogenic coating, tradenamed Anthron. Anthron-coated thermodilution catheters show excellent antithrombogenicity due to continuous release of heparin from its surface to the blood stream in animal experiments. As controls, a poly (vinyl chloride) thermodilution catheter was evaluated in the similar manner. All of Anthron-coated thermodilution catheters were completely free from thrombus formation and kept excellent sensing functions for more than 3 days, while in control catheters severe thrombus formations were found both on the surfaces of the catheters and blood vessels. The sensing functions of the control catheters deteriorated with passage of time because of the deposition of the blood constituents on the thermistor.     

Chitosan/poly(vinyl alcohol) blending hydrogel coating improves the surface characteristics of segmented polyurethane urethral catheters

Segmented polyurethane (SPU) is commonly used to manufacture urethral catheters. Surface modifications for SPU catheters are needed to reduce friction and protein adsorption, in order to minimize catheter-related complications, including urethral trauma, encrustation, catheter obstruction, bacterial colonization, and infection. In this study, a four-step surface modification method was developed to create a thin lubricious layer of chitosan/poly(vinyl alcohol) (PVA) hydrogel on the SPU catheter. Modification steps included oxidation of the SPU surface, functionalities modification, carbodiimide reaction and coupling, and hydrogel crosslinking. The success of each modification step was confirmed by Fourier transform infrared spectroscopy. Measurement of the water contact angle revealed that hydrogel coating created a highly hydrophilic surface and atomic force microscope analyses demonstrated that the surface was slippery. Protein absorption of the SPU catheter was significantly reduced by coating hydrogel. Chitosan in the hydrogel could provide antimicrobial activity, and the hydrogel coating SPU samples showed significant antibacterial effects in this study. In summary, the four-step modification method developed in this study provided a simple and effective way to coat the surface of SPU catheters with a chitosan/PVA blending hydrogel that could help to minimize the risk of complications related to the use of urethral catheters.     

Gentamicin-releasing urethral catheter for short-term catheterization

Urethral catheters, widely used for the drainage of the bladder, are associated with most urinary tract infections (UTIs) that account for 40% of all episodes occurring in acute-care hospitals. This study aimed to develop a gentamicin-releasing catheter that effectively prevents UTIs for short-term catheterization. For physical loading of gentamicin, the urethral catheters were coated by the simple dipping method with poly(ethylene-co-vinyl acetate) (EVA) and EVA/poly(ethylene oxide) (PEO) blends containing gentamicin. By varying the molecular weight (MW) and contents of PEO in the blends, various catheter surfaces were produced. In vitro drug release studies demonstrated that all the coated catheters exhibited sustained release up to 7 days; however, the release pattern was significantly dependant on the coating layers. Of the coated catheters, EVA/PEO (MW = 100k)-coated catheters were utilized to evaluate the antibacterial activity using an inhibition zone test, since they showed a promising drug release behavior and had PEO-rich biocompatible surfaces. In accordance with drug release behavior, EVA/PEO-coated catheters exhibited antibacterial activities for 7 days against Proteus vulgaris, Staphylococcus aureus and Staphylococcus epidermidis. These results imply that the catheters coated with EVA/PEO have a potential for short-term catheterization.     

Analysis of cellular morphology, adhesion, and proliferation on uncoated and differently coated PVC tubes used in extracorporeal circulation (ECC)

The biggest challenge to improve extracorporeal circulation (ECC) circuits lays on avoiding platelet adhesion to their surfaces, because this contributes to thrombus formation, resulting in the activation of blood coagulation. One approach to minimize this effect is to improve the biocompatibility of ECC circuits by modifying their surfaces. This can be achieved by coating them with heparin or phospholipids. The present study investigated the adhesion and morphology characteristics of fibroblastic and blood cells cultured on uncoated poly (vinyl) chloride PVC tubes as well as on heparin, phosphatidylcholine (DMPC), and phosphatidylethanolamine (DMPE) -coated tubing. The results showed the importance of uniform coating regardless of the substance used, because the coatings cover the grooves on PVC surfaces, which favor cell adhesion. The comparison among the three different coatings showed the best biocompatibility results for the PVC tubes coated with heparin, followed by the coating with DMPE and with DMPC. For all coated tubes, cells did not spread on the PVC surfaces and, consequently, did not adhere to their surfaces, increasing the overall biocompatibility of PVC tubes. However, possible DMPE's alkylation, caused by sterilization, resulted in increased material hydrophobicity, which explains the decrease in fibroblastic adhesion. Furthermore, sterilization of DMPC-PVC improves its hydrophilic character, also decreasing adhesion. Based on these results, coating PVC with the phospholipids DMPC and DMPE seems to be a promising technique to improve the biocompatibility of PVC tubes, and is worthy of further investigation.     

Norfloxacin-releasing urethral catheter for long-term catheterization

Norfloxacin-releasing urethral catheters were prepared for the purpose of preventing urinary tract infections during long-term catheterization. The outer and inner surfaces of the catheters were coated with poly(ethylene-co-vinyl acetate) (EVA) and an amphiphilic multiblock co-polymer (PEO2kPDMS), composed of poly(ethylene oxide) and poly(dimethyl siloxane). Norfloxacin, a fluoroquinolone synthetic antibiotic, was impregnated into a coating layer. The in vitro drug release behavior was monitored for 30 days, the surface topography was investigated using scanning electron microscopy (SEM) and the antibacterial activity against different bacteria implicated in urinary tract infection was evaluated by the in vitro inhibition zone test. All the coated catheters showed continuous delivery of norfloxacin for up to 30 days owing to hydrophobic natures of norfloxacin and EVA. PEO2kPDMS incorporated in a coating layer produced a smooth and uniform surface. The coated catheters created considerable inhibition zones for 10 days against Escherichia coli. Klebsiella pneumoniae and Proteus vulgaris, indicating the continuous release of norfloxacin. Overall, it was evident that the catheters coated with EVA/PEO2kPDMS blends containing norfloxacin have a promising potential for the clinical use in patients undergoing long-term catheterization.     

Norfloxacin-releasing urethral catheter for long-term catheterization

Norfloxacin-releasing urethral catheters were prepared for the purpose of preventing urinary tract infections during long-term catheterization. The outer and inner surfaces of the catheters were coated with poly(ethylene-co-vinyl acetate) (EVA) and an amphiphilic multiblock co-polymer (PEO_2kPDMS), composed of poly(ethylene oxide) and poly(dimethyl siloxane). Norfloxacin, a fluoroquinolone synthetic antibiotic, was impregnated into a coating layer. The in vitro drug release behavior was monitored for 30 days, the surface topography was investigated using scanning electron microscopy (SEM) and the antibacterial activity against different bacteria implicated in urinary tract infection was evaluated by the in vitro inhibition zone test. All the coated catheters showed continuous delivery of norfloxacin for up to 30 days owing to hydrophobic natures of norfloxacin and EVA. PEO_2kPDMS incorporated in a coating layer produced a smooth and uniform surface. The coated catheters created considerable inhibition zones for 10 days against Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris, indicating the continuous release of norfloxacin. Overall, it was evident that the catheters coated with EVA/PEO_2kPDMS blends containing norfloxacin have a promising potential for the clinical use in patients undergoing long-term catheterization.     

Surface modification and evaluation of some commonly used catheter materials. I. Surface properties

Double catheter systems consisting of a stiff outer catheter and a flexible, buoyant, flow-directed, inner catheter which is often balloon-tipped have been employed with increasing frequency recently in both therapeutic and diagnostic procedures. Their use, however, has been restricted because of the excessive friction generated between the two catheters. In an attempt to decrease friction between polymers commonly used as catheter materials, oxidation of polyethylene, fluorinated ethylene-propylene copolymer, poly(vinyl chloride), silicone rubber, and polystyrene surfaces was induced by exposing the polymers to radio frequency glow discharge (RFGD) in a helium environment. All polymers were surface characterized utilizing x-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and contact angle measurements before and after oxidation. This article describes the materials and methods used to fabricate and characterize the polymer surfaces and the results of the characterization. The results indicate that increases in oxygen concentration at the surface of the polymers and decreases in air-water contact angles occur with increased RFGD exposure time. Plateau values were usually obtained after 5-30 s exposure time, yet no apparent changes in surface topography were noted by scanning electron microscopy. The hydrophilic surfaces produced were stable for up to three months storage time in air.     

介入治疗导管表面润滑处理研究

介绍了一种用于介入治疗导管表面润滑处理的方法。对润滑涂层的作用原理、涂覆工艺等进行了论述，并讨论了用于润滑处理的聚合物、溶剂的选择及润滑处理后介入治疗导管表面摩擦系数的变化情况。通过生物安全性试验和临床试用，证明了本方法是安全可靠的。     

Radiation grafting of hydrophilic monomers on to plasticized poly(vinyl chloride) sheets. II. Migration behaviour of the plasticizer from N-vinyl pyrrolidone grafted sheets

The grafting of N-vinyl pyrrolidone, a hydrophilic monomer, on to flexible poly(vinyl chloride) sheets used in medical applications using ionizing radiation from a 60Co source was studied. The graft yield was found to increase linearly with monomer concentration and also with increasing radiation doses. The migration of the plasticizer di-(2-ethylhexyl)phthalate into a strong organic extractant such as n-hexane was studied at different time intervals for different grafted systems of poly(vinyl chloride) at 30 degrees C. The results indicated a drastic reduction in the leaching of the plasticizer from grafted systems versus ungrafted controls. Incorporation of ethylene dimethacrylate cross-linker during grafting did not seem to affect the graft yield considerably but appeared to further reduce the plasticizer migration. Surface energy calculations of the grafted samples indicate that the surfaces are highly hydrophilic compared to ungrafted poly(vinyl chloride) and the polar and dispersion components tend to vary with increasing cross-linker concentration.     

Gentamicin-releasing urethral catheter for short-term catheterization

Urethral catheters, widely used for the drainage of the bladder, are associated with most urinary tract infections (UTIs) that account for 40% of all episodes occurring in acute-care hospitals. This study aimed to develop a gentamicin-releasing catheter that effectively prevents UTIs for short-term catheterization. For physical loading of gentamicin, the urethral catheters were coated by the simple dipping method with poly(ethylene-co-vinyl acetate) (EVA) and EVA/poly(ethylene oxide) (PEO) blends containing gentamicin. By varying the molecular weight (MW) and contents of PEO in the blends, various catheter surfaces were produced. In vitro drug release studies demonstrated that all the coated catheters exhibited sustained release up to 7 days; however, the release pattern was significantly dependant on the coating layers. Of the coated catheters, EVA/PEO (MW = 100k)-coated catheters were utilized to evaluate the antibacterial activity using an inhibition zone test, since they showed a promising drug release behavior and had PEO-rich biocompatible surfaces. In accordance with drug release behavior, EVA/PEO-coated catheters exhibited antibacterial activities for 7 days against Proteus vulgaris, Staphylococcus aureus and Staphylococcus epidermidis. These results imply that the catheters coated with EVA/PEO have a potential for short-term catheterization.     

All‐Dry Hydrophobic Functionalization of Paper Surfaces for Efficient Transfer of CVD Graphene

In this study, the successful transfer of chemical vapor deposition (CVD)‐grown graphene on an ordinary printing paper surface is demonstrated. Pristine paper is not a suitable substrate for graphene transfer because of its fragile and hydrophilic nature against the chemicals used during the transfer process. Two different fluoroalkyl polymers, namely poly(hexafluorobutyl acrylate) (PHFBA) and poly(perfluorodecyl acrylate) (PPFDA) are coated on paper surfaces by an initiated CVD (iCVD) technique to make the paper surfaces hydrophobic. Hydrophobicity is found to be an important factor in order for the graphene to be transferred onto the paper substrate. Although surfaces coated with PPFDA possess better hydrophobicity owing to their longer perfluoroalkyl group and higher roughness, the graphene transfer is found to be more successful on a PHFBA‐coated surface. A thin film of PHFBA on the paper surface acts as a prime layer for effective and defect‐free transfer of graphene and makes the paper surface ideal and robust during the graphene transfer process. The as‐transferred graphene layer on the PHFBA‐coated paper surface shows high conductivity values, even after repeated folding and flattening cycles.     

Modification of central venous catheter polymers to prevent in vitro microbial colonisation

The efficacy of an antimicrobial catheter for the prevention of bacterial colonisation was investigated. The catheter was hydrophilic coated (Hydrocath) and impregnated with the quaternary ammonium antimicrobial agent, benzalkonium chloride (BZC). Microbial colonisation of this central venous catheter was compared to that of polyurethane catheters with or without a hydrophilic coating. Adherence of five strains ofStaphylococcus epidermidis to the three catheter types was determined with a microbial colonisation model. Adherence of three strains ofStaphylococcus epidermidis to Hydrocath catheters was significantly reduced in comparison to polyurethane catheters (p<0.01). BZC-impregnated Hydrocath catheters prevented bacterial colonisation of both the internal and external catheter surfaces (p<0.01). These results were confirmed by scanning electron microscopy. The findings demonstrate that hydrophilic-coated Hydrocath catheters can inhibit bacterial adherence in vitro. Bacterial colonisation was further restricted by the addition of BZC to these coated catheters.     

Enhanced wear resistance of orthopaedic bearing due to the cross-linking of poly(MPC) graft chains induced by gamma-ray irradiation

We assumed that the extra energy supplied by gamma-ray irradiation produced cross-links in 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer grafted cross-linked polyethylene (CLPE-g-MPC) and investigated its effects on the tribological properties of CLPE-g-MPC. In this study, we found that the gamma-ray irradiation produced cross-links in three kinds of regions of CLPE-g-MPC: poly(MPC) layer, CLPE-MPC interface, and CLPE substrate. The dynamic coefficient of friction of CLPE-g-MPC slightly increased with increasing irradiation doses. After the simulator test, both the nonsterilized and gamma-ray sterilized CLPE-g-MPC cups exhibited lower wear than the untreated CLPE ones. In particular, the gamma-ray sterilized CLPE-g-MPC cups showed extremely low and stable wear. As for the nonsterilized CLPE-g-MPC cups, the weight change varied with each cup. When the CLPE surface is modified by poly(MPC) grafting, the MPC graft polymer leads to a significant reduction in the sliding friction between the surfaces that are grafted because water thin films formed can behave as extremely efficient lubricants. Such a cross-link of poly(MPC) slightly increases the friction of CLPE by gamma-ray irradiation but provides a stable wear resistant layer on the friction surface. The cross-links formed by gamma-ray irradiation would give further longevity to the CLPE-g-MPC cups.     

Hydrophilic-hydrophobic microdomain surfaces having an ability to suppress platelet aggregation and their in vitro antithrombogenicity

Block copolymers were synthesized by a coupling reaction of hydrophilic chains of poly(2-hydroxyethyl methacrylate) (PHEMA) with hydrophobic chains of polystyrene (PSt), or poly(dimethyl siloxane) (PDMS). Microstructures of films of the block copolymers exhibited a hydrophilic-hydrophobic microphase separated structure. For evaluation of in vivo antithrombogenicity, small diameter tubes (1.5 mm I.D. and 20 cm length) coated by the copolymers on their internal surfaces were implanted in rabbits as arteriovenous shunts. Occlusion times of the tubes, measured by formation of thrombus, were three days for PHEMA, two days for PSt, and three days for PDMS. The block copolymers showed excellent antithrombogenic properties: occlusion times were 20 days for HEMA-St block copolymer and 12 days for HEMA-DMS block copolymers. In vitro examination of polymer-platelet interaction in terms of platelet adhesion and aggregation, which are important initial processes of blood coagulation, demonstrated suppressed adhesion and aggregation on microdomain surfaces constructed of hydrophilic and hydrophobic block copolymers. From both in vivo and in vitro examination, it was concluded that HEMA-St and HEMA-DMS block copolymers showed promising antithrombogenic activities by suppressing activation and aggregation of platelets.     

Poly(ethylene oxide) surfactant polymers

We report on a series of structurally well-defined surfactant polymers that undergo surface-induced self-assembly on hydrophobic biomaterial surfaces. The surfactant polymers consist of a poly(vinyl amine) backbone with poly(ethylene oxide) and hexanal pendant groups. The poly(vinyl amine) (PVAm) was synthesized by hydrolysis of poly(N-vinyl formamide) following free radical polymerization of N-vinyl formamide. Hexanal and aldehyde-terminated poly(ethylene oxide) (PEO) were simultaneously attached to PVAm via reductive amination. Surfactant polymers with different PEO:hexanal ratios and hydrophilic/hydrophobic balances were prepared, and characterized by FT-IR, 1H-NMR and XPS spectroscopies. Surface active properties at the air/water interface were determined by surface tension measurements. Surface activity at a solid surface/water interface was demonstrated by atomic force microscopy, showing epitaxially molecular alignment for surfactant polymers adsorbed on highly oriented pyrolytic graphite. The surfactant polymers described in this report can be adapted for simple non-covalent surface modification of biomaterials and hydrophobic surfaces to provide highly hydrated interfaces.     

Apatite Coating of Electrospun PLGA Fibers Using a PVA Vehicle System Carrying Calcium Ions

A novel method to coat electrospun poly(D,L-lactic-co-glycolic acid) (PLGA) fiber surfaces evenly and efficiently with low-crystalline carbonate apatite crystals using a poly(vinyl alcohol) (PVA) vehicle system carrying calcium ions was presented. A non-woven PLGA fabric was prepared by electrospinning: a 10 wt% PLGA solution was prepared using 1,1,3,3-hexafluoro-2-propanol as a solvent and electrospun under a electrical field of 1 kV/cm using a syringe pump with a flowing rate of 3 ml/h. The non-woven PLGA fabric, 12 mm in diameter and 1 mm in thickness, was cut and then coated with a PVA solution containing calcium chloride dihydrate (specimen PPC). As controls, pure non-woven PLGA fabric (specimen P) and fabric coated with a calcium chloride dihydrate solution without PVA (specimen PC) were also prepared. Three specimens were exposed to simulated body fluid for 1 week and this exposure led to form uniform and complete apatite coating layer on the fiber surfaces of specimen PPC. However, no apatite had formed to the fiber surfaces of specimen P and only inhomogeneous coating occurred on the fiber surfaces of specimen PC. These results were explained in terms of the calcium chelating and adhesive properties of PVA vehicle system. The practical implication of the results is that this method provides a simple but efficient technique for coating the fiber surface of an initially non-bioactive material with low-crystalline carbonate apatite.     

Blends of stearyl poly(ethylene oxide) coupling-polymer in chitosan as coating materials for polyurethane intravascular catheters.

To optimize the surface biocompatibility of the intravascular catheter, an amphiphilic coupling-polymer of stearyl poly (ethylene oxide) -co- 4,4'-methylene diphenyl diisocyanate-co- stearyl poly (ethylene oxide), for short MSPEO, was specially designed as the surface modifying additive (SMA). The blend of MSPEO in chitosan was coated on the outer wall of the catheters by the dip-coating method. The surface analysis was carried out by ATR-FTIR and contact angle measurements. The surface enrichment of MSPEO was confirmed. On the water interface, the larger the molecular weight of PEO was, the higher the surface enrichment. While on air interface, the case was the contrary. Three kinds of static test of clotting time, plasma recalcification time (PRT), prothrombin time (PT), and thrombin time (TT), as well as the static platelet adhesion experiment were carried out. The results indicated that the coated surface could resist the clotting effectively. In order to test the blood-compatibility of the coated catheters under a shear of blood flow, the dynamic experiment was performed through a closed-loop tubular system with the shear rate of 1500 s(-1). The results of blood regular testing at six different times (0, 5,10, 20, 30, and 60 min) indicated that the biocompatibility of the coating was nearly ideal. Finally, the SMA-MSPEO was proved to be non-chronic-toxic by animal experiments with rats and suitable as a coating material for clinical use.     

Poly(dimethylsiloxane) thin films as biocompatible coatings for microfluidic devices: cell culture and flow studies with glial cells

Oxygen plasma treatment of poly(dimethylsiloxane) (PDMS) thin films produced a hydrophilic surface that was biocompatible and resistant to biofouling in microfluidic studies. Thin film coatings of PDMS were previously developed to provide protection for semiconductor-based microoptical devices from rapid degradation by biofluids. However, the hydrophobic surface of native PDMS induced rapid clogging of microfluidic channels with glial cells. To evaluate the various issues of surface hydrophobicity and chemistry on material biocompatibility, we tested both native and oxidized PDMS (ox-PDMS) coatings as well as bare silicon and hydrophobic alkane and hydrophilic oligoethylene glycol silane monolayer coated under both cell culture and microfluidic studies. For the culture studies, the observed trend was that the hydrophilic surfaces supported cell adhesion and growth, whereas the hydrophobic ones were inhibitive. However, for the fluidic studies, a glass-silicon microfluidic device coated with the hydrophilic ox-PDMS had an unperturbed flow rate over 14 min of operation, whereas the uncoated device suffered a loss in rate of 12%, and the native PDMS coating showed a loss of nearly 40%. Possible protein modification of the surfaces from the culture medium also were examined with adsorbed films of albumin, collagen, and fibrinogen to evaluate their effect on cell adhesion.     

Friction and wear behavior of poly(vinyl alcohol)/poly(vinyl pyrrolidone) hydrogels for articular cartilage replacement

Many hydrogels have been proposed as articular cartilage replacements as an alternative to partial or total joint replacements. In the current study, poly(vinyl alcohol)/poly(vinyl pyrrolidone) (PVA/PVP) hydrogels were investigated as potential cartilage replacements by investigating their in vitro wear and friction characteristics in a pin-on-disk setup. A three-factor variable-level experiment was designed to study the wear and friction characteristics of PVA/PVP hydrogels. The three different factors studied were (a) polymer content of PVA/PVP hydrogels, (b) load, and (c) effect of lubricant. Twelve tests were conducted, with each lasting 100,000 cycles against Co-Cr pins. The average coefficient of friction for synovial fluid lubrication was a low 0.035 compared with 0.1 for bovine serum lubrication. Frictional behavior of PVA/PVP hydrogels did not follow Amonton's law of friction. Wear of the hydrogels was quantified by measuring their dry masses before and after the tests. Higher polymer content significantly reduced the wear of hydrogel samples with 15% PVA/PVP samples, showing an average dry polymer loss of 4.74% compared with 6.05% for 10% PVA/PVP samples. A trend change was observed in both the friction and wear characteristics of PVA/PVP hydrogels at 125 N load, suggesting a transition in the lubricating mechanism at the pin-hydrogel interface at the critical 125 N load.     

A preliminary report on a novel electrospray technique for nanoparticle based biomedical implants coating: precision electrospraying

The compatibility and biological efficacy of biomedical implants can be enhanced by coating their surface with appropriate agents. For predictable functioning of implants in situ, it is often desirable to obtain an extremely uniform coating thickness without effects on component dimensions or functions. Conventional coating techniques require rigorous processing conditions and often have limited adhesion and composition properties. In the present study, the authors report a novel precision electrospraying technique that allows both degradable and nondegradable coatings to be placed. Thin metallic slabs, springs, and biodegradable sintered microsphere scaffolds were coated with poly(lactide-co-glycolide) (PLAGA) using this technique. The effects of process parameters such as coating material concentration and applied voltage were studied using PLAGA and poly(ethylene glycol) coatings. Morphologies of coated surfaces were qualitatively characterized by scanning electron microscopy. Qualitative observations suggested that the coatings were composed of particles of various size/shape and agglomerates with different porous architectures. PLAGA coatings of uniform thickness were observed on all surfaces. Spherical nanoparticle poly(ethylene glycol) coatings (462-930 nm) were observed at all concentrations studied. This study found that the precision electrospraying technique is elegant, rapid, and reproducible with precise control over coating thickness (mum to mm) and is a useful alternative method for surface modification of biomedical implants.