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Hydrophilic polyurethane versus autologous femoral vein as substitutes in the femoral arteries of dogs: quantification of platelets and fibrin deposits.

Hydrophilic, microporous polyurethane vascular prostheses displayed good mechanical characteristics and the behaviour in vitro was excellent. The in-vivo results were, however, disappointing. To obtain a better understanding of the phenomena involved in the acute and early thrombosis, we implanted the polyurethane graft in the canine left femoral artery and an autologous femoral vein in the right for 4 and 24 h. At 4 h, one polyurethane graft was totally occluded and the other two were close to complete occlusion; at 24 h, none was patent. On the other hand, all autologous veins were patent. The thrombotic matrix incorporating both platelets and fibrinogen, quantified by labelling, was anchored along the anastomotic lines. This study confirms that polyurethane occlusion is initiated by hyperplastic reaction, but does not explain why.

Animals

Effect of polyol molecular weight on the physical properties and haemocompatibility of polyurethanes containing polyethylene oxide macroglycols.

The physical properties and haemocompatibility of polyurethanes containing polyethylene oxide (PEO) of varying molecular weights but constant weight fraction of hard segment are investigated. The PEO molecular weights studied were 600, 1450 and 8000. Analysis of polyurethane phase separation and crystallinity using dynamic-mechanical analysis and differential scanning calorimetry show that the degree of phase separation and crystallinity increase with polyol molecular weight, but level off at the highest molecular weights. The degree of water absorption increases substantially with increasing PEO molecular weight, levelling off at the highest molecular weight. Tensile data show a maximum in extensibility at a polyethylene glycol (PEG) molecular weight of 1450, while ultimate strength increases with increasing segment length. When the materials are hydrated, there is a significant drop in the modulus, ultimate stress and ultimate elongation. Dynamic contact angle measurements show that surface hydrophobicity decreases as the soft segment molecular weight increases. Using electron spectroscopy for chemical analysis (ESCA) to determine the surface composition of these polyurethanes, it was found that the hard segment content at the surface increases as the polyol block length decreases. The haemocompatibility of these polyurethanes was investigated in an ex vivo canine blood-contacting model. Only for the shortest block length studied, PEG-600, are differences in blood compatibility observed. This material was found to be the most thrombogenic. The PEG-1450 sample shows comparable blood compatibility to PEG-8000.

Animals

Neutrophil-mediated degradation of segmented polyurethanes.

The biostability of polyurethanes was evaluated using a human neutrophil cell culture. The polymers were synthesized with 14C radiolabelled components incorporated into the polyurethane chain and the amount of radiolabel released during exposure to cells and medium was used as a marker for material degradation. The effect of diisocyanate, soft segment and chain extender chemistry on the susceptibility of polymer degradation was examined. All polymers showed a release of material into the tissue culture medium which was unrelated to the cells. A significant cell-dependent release of radiolabel-containing material was found from one of the polymers (a polyester urea-urethane, TDI/PCL/ED) which increased linearly up to 96 h. The polyether-containing polyurethanes showed no significant cell-mediated degradation under similar conditions as measured by radiolabel release. Scanning electron microscopy (SEM) showed that the cells adhered to the different polyurethanes. However, no effect of neutrophils on polymer structure could be detected by this technique. The cellular response to each polymer was evaluated by measuring release of elastase-like activity (ELA) into the tissue culture media. After 24h TDI/PCL/ED showed the highest levels of ELA in the tissue culture medium. When TDI/PCL/ED was incubated with commercial elastase in vitro, a significant release of radiolabel was found which was comparable to the amount of radiolabelled material released from this polymer in contact with the neutrophils in culture. No significant amount of radiolabel was released from the corresponding polyether material (TDI/PTMO/ED) under similar conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodegradation, Environmental

Hybrid biomaterials based on the interaction of polyurethane oligomers with porcine pericardium.

Hybrid biomaterials have been produced by the interaction of polyurethane oligomers with both fresh and glutaraldehyde-fixed porcine pericardium. The hybrid biomaterials so formed were translucent with occasional white streaks and/or spots, had increased stiffness (to touch) but remained pliable. No shrinkage temperature was detected for fresh porcine pericardium hybrid up to 100 degrees C compared to porcine pericardium (approximately 67 degrees C) and glutaraldehyde-fixed porcine pericardium (approximately 87 degrees C). Amino acid analysis of the fresh porcine pericardium hybrid showed a reduction in lysine content after active isocyanate-terminated polyurethane oligomers exposure, indicating cross-linking between the polymer and tissue. Histological examination of the hybrid material shows a thin grey coating on both surfaces of the tissue, implying at least surface cross-linking of the tissue with polyurethane. The results suggest that fresh porcine pericardium can be reacted with active isocyanate-terminated polyurethane oligomers to produce hybrid biomaterials with covalent bonding.

Animals

Physical and biological effects of a surface coating procedure on polyurethane catheters.

Central venous catheters are widely used in clinical practice; however, complications such as venous thrombosis or infection are frequent. The physical and biological effects of a coating procedure designed to improve the blood-contacting properties of polyurethane central venous catheters (CVCs) were studied. The surface atomic composition of poly(vinyl pyrrolidone) (PVP)-coated or uncoated Pellethane single lumen CVCs was characterized by electron spectroscopy for chemical analysis (ESCA), which confirmed the presence of an oxygen-rich PVP layer on the former material. Topological analysis of both single and triple lumen CVCs by scanning force microscopy (SFM) revealed a very smooth surface in PVP-coated catheters compared to the more frequent surface irregularities found either in uncoated Pellethane or in four additional randomly selected, commercially available triple lumen polyurethane CVCs. The PVP-coated Pellethane showed a strong reduction in either fibrinogen or fibronectin adsorption compared to all other PVP-free polyurethane CVCs. This decreased protein adsorption led to a proportional reduction in protein-mediated adhesion of either Staphylococcus aureus or Staphylococcus epidermidis and in the binding of a monoclonal antibody directed against the cell-binding domain of fibronectin. Increased surface smoothness and hydrophilic properties of polyurethane CVCs might decrease the risk of bacterial colonization and infection.

Adsorption

Polyurethane film (Opsite) vs. impregnated gauze (Jelonet) in the treatment of outpatient burns: a prospective, randomized study.

As it has been shown that re-epithelialization of partial skin thickness wounds can be accelerated if the wound is kept moist, a prospective, randomized clinical study compared the water vapour-semipermeable polyurethane film, Opsite, with the conventional impregnated gauze dressing, Jelonet, in the treatment of outpatient partial skin thickness burns. Fifty-five patients were included: 30 were treated with the polyurethane film and 25 with the conventional dressing. The patients were followed at regular intervals until healing had occurred and were seen 3 months later for evaluation of residual scars and pigmentation. The burns treated with polyurethane films healed with a median of 10 days, while the conventionally treated burns healed with a median of 7 days (P greater than 0.05). Residual scars were noted in 21 per cent of the patients treated with polyurethane films and in 8 per cent treated conventionally (P greater than 0.05). Prophylactic methods should be publicly stressed since one-quarter of the patients were children of 3 years or less who were scalded by split hot liquids. Furthermore the patients' wounds were only briefly cooled before attending medical care. With small burns we advise that cooling should be prolonged until the pain fades then professional assistance should be sought.

Adolescent

Comparison of transverse strength and dimensional variations between die stone, die epoxy resin, and die polyurethane resin.

This study compared transverse strength and dimensional variations of die stone, epoxy resin, and polyurethane resin. The polyurethane resin was tested unfilled, then filled with 20%, 40%, and 60% silica, by weight. Transverse strength was evaluated for five test strips for each material, and an original calibration plate technique closely simulating intraoral conditions was introduced to evaluate dimensional accuracy. Two series of five measurements for dimensional variations were recorded on each test strip. The first series was 15 minutes after removal from mold and the second series of 5 minutes a week later. The results were computed with a parametric ANOVA and Scheffe's test at 95% confidence level (p < or = 0.05). These results confirmed that die stone recorded the least dimensional change but was rigid and brittle, whereas epoxy resin and polyurethane resin had suitable mechanical properties including greater dimensional variations. Incorporating silica filler in polyurethane resins also reduced their transverse strength and sponsored minimal dimensional variations.

Analysis of Variance

Physical property analysis and bacterial adhesion on a series of phosphonated polyurethanes.

Glycerophosphorylcholine (GPC) was incorporated as the chain extender in a series of poly(tetramethylene oxide)-based polyurethane block copolymers. In order to determine the feasibility of use of these polyurethanes in biomedical devices, the effects of GPC incorporation on physical properties were studied. The effect of soft-segment molecular weight was also investigated. Biocompatibility of these materials was studied with regard to bacterial adhesion and protein deposition. Tensile testing showed that as GPC content increased, elongation at break decreased, while Young's modulus increased. Differential scanning calorimetry (DSC) results showed slightly decreased glass transition temperatures (Tgs) with increasing GPC content, indicating increased phase separation. Dynamic mechanical analysis (DMA) confirmed the decrease in Tg and the increase in rubbery plateau modulus with increasing GPC content. Water absorption was also increased with GPC content. Decreased bacterial adhesion was found on the GPC-containing materials compared to other functionalized polyurethanes. These experiments were carried out in a radial flow chamber utilizing automated video microscopy. Bacterial attachment was found to be lower on the GPC-containing polyurethanes both in the absence of and after pre-adsorption with plasma proteins.

Bacterial Adhesion

Controlled release of antibiotics from biomedical polyurethanes: morphological and structural features.

Polymer-associated infections are of increasing importance. Antistaphylococcal antimicrobial substances (ciprofloxacin, gentamycin, fosfomycin, flucloxacillin) were incorporated into polyurethanes by the solvent casting technique. Drug release rates, bacterial colonization and morphological features were evaluated to predict and understand the antimicrobial activity of these delivery systems. Drug release characteristics were investigated by standard bioassay and high-performance liquid chromatography (HPLC), and the physico-chemical mechanisms of the delivery were discussed. Ciprofloxacin hydrochloride showed a fast initial release rate, whereas gentamicin-base was characterized by a more continuous release type of behaviour. Bacterial colonization to the antibiotic-loaded polyurethanes was inhibited effectively by preparations showing a slower but more sustained antimicrobial delivery. Polyurethane-antibiotic combinations were most homogeneous for gentamicin-base and flucloxacillin as shown by scanning electron microscopy (SEM). In polymers loaded with fosfomycin and ciprofloxacin a granular structure of the crystallized drug embedded in the polyurethane matrix could be demonstrated. Physico-chemical similarity of the polymeric material and the antibiotics is important for the homogeneity of polymer-antibiotic combinations. High homogeneity is required for a sustained and prolonged release over time and effective inhibition of bacterial colonization.

Anti-Bacterial Agents

Neutrophil adhesion on phosphorylcholine-containing polyurethanes.

Polyurethanes have been synthesized using glycerophosphorylcholine (GPC) as a chain extender. By altering the ratio of GPC to butanediol (BD), a series of polymers was obtained composed of different contents of phosphorylcholine. Bulk and surface characterization of the polymers was carried out. Differential scanning calorimetry and dynamic mechanical analysis showed that the polymer with the highest phosphorylcholine content (PU-GPC-20) had the lowest soft segment Tg and the highest tensile strength and Young's modulus among the polymers studied. This is due to the high degree of microphase separation in PU-GPC-20 as a result of by ionic aggregation and hydrogen bonding from the zwitterionic phosphorylcholine moiety. PU-GPC-20 contained approximately 20 wt%, of glycerophosphorylcholine. Dynamic contact angle analysis showed that these polymers, especially the ones with high phosphorylcholine content, rearranged themselves to minimize their interfacial tension upon contacting an aqueous environment. Under shear rates of from 20 to 120 s(-1), neutrophils did not adhere to PU-GPC-20. Under similar conditions neutrophil adhesion was observed only at 20 s(-1) on PU-GPC-10, PU-GPC-5 and on the control polyurethane (PU-base). Cell spreading was observed on the control polyurethane but not on any of the other surfaces. The incorporation of phosphorylcholine into the polyurethane backbone effectively reduced neutrophil adhesion and thus potentially could result in lower inflammatory and foreign body responses.

Absorption

Preparation of porous polyurethane particles and their use in enzyme immobilization.

Porous polyurethane particles were prepared as follows: (1) Two low molecular weight polymers, namely, poly[methylene(polyphenyl isocyanate)] and poly(propylene glycol) were mixed with stirring at room temperature and allowed to react. (2) The reacted mixture was dispersed with stirring in mineral oil containing small amounts of water, the catalyst dibutyltin dilaurate, and CaCO3 powder. In the presence of the catalyst, the reaction between the two polymers proceeded to completion. Small particles of polyurethane are thus formed which contain mineral oil and CaCO3 as porogens. The particles obtained, separated by filtration, were treated with a solution of HCl in order to generate additional pores, extracted with benzene to eliminate the mineral oil present in the pores, and finally subjected to drying and sieving. The particles were investigated by scanning electron microscopy (SEM), infrared (IR) spectroscopy, and specific surface area measurements. Lipase from Candida rugosa was immobilized by adsorption on the porous polyurethane particles and cross-linked with glutaraldehyde to enhance the stability of the immobilization. The biocatalytic particles were used for the hydrolysis of triacylglycerides. The high activity of the immobilized enzyme, which per enzyme molecule can be higher than that of the free enzyme, reveals that the porous polyurethane particles constitute excellent supports for lipase.

Emulsions

Epicardial administration of ibutilide from polyurethane matrices: effects on defibrillation threshold and electrophysiologic parameters.

Polymer-drug composites known as controlled-release systems have been used effectively to prevent and treat ventricular arrhythmias in experimental studies. We wished to determine if such systems could be useful in reducing ventricular defibrillation energy requirements in an acute canine model without producing undesirable electrophysiologic effects. Ibutilide-polyurethane monolithic controlled-release matrices were formulated with ibutilide fumarate and a polyether polyurethane. In vitro drug-release characteristics of the drug matrices were determined. Two formulations were investigated: (a) 20% ibutilide by weight in polyether polyurethane, and (b) 4% ibutilide/16% dimethyl tartrate in polyurethane. Based on in vitro release studies, 20% ibutilide matrices (25 mg) would provide a 25-kg dog with a dose of 25 micrograms/kg ibutilide in a 2-h acute experimental period, and 4% ibutilide matrices were estimated to provide 3.5 micrograms/kg. We used each of these types of matrices in acute open-chest dog studies to assess electrophysiologic effects and the influence of epicardial controlled-release ibutilide, as compared with intravenous (i.v.) administration, on defibrillation energy thresholds (DFTs), using epicardial defibrillation electrodes. In monophasic defibrillation waveform studies, 20% matrices significantly decreased DFT as compared with a predrug control period [2.54 +/- 0.59 (mean +/- SEM) vs. 7.23 +/- 1.73 J, respectively, p = 0.038]. Administration of the same dose i.v. did not cause significant reduction in energy requirement. With a biphasic defibrillation waveform, 4% ibutilide matrices significantly decreased DFT as compared with control (2.53 +/- 0.34 vs. 3.42 +/- 0.46 J, respectively, p = 0.003). Administration of an equivalent i.v. dose did not cause a significant reduction in biphasic energy requirement. Both types of controlled-release systems significantly prolonged refractoriness and conduction times of ventricular extrastimuli as compared with vehicle. No proarrhythmia events were observed. Epicardial polymeric controlled-release ibutilide significantly prolonged ventricular refractoriness and conduction and thus may enhance antiarrhythmia activity. In addition, controlled-release ibutilide formulations significantly decreased DFT requirements. Thus, ibutilide-polymeric controlled-release matrix systems may be useful in conjunction with implantable defibrillators in preventing ventricular arrhythmias and reducing defibrillation energy requirements.

Animals

Natural-Y Même polyurethane versus smooth silicone: analysis of the soft-tissue interaction from 3 days to 1 year in the rat animal model.

The polyurethane foam-covered breast prosthesis is experiencing increased clinical use. The polyurethane is felt to be responsible for altering capsule formation and reducing the contracture rate. This study characterizes the soft-tissue response to the Natural-Y Même polyurethane foam versus smooth silicone in a rat model. Implants were fashioned from an unbacked polyurethane foam specimen used to cover the Natural-Y prosthesis, a silicone shell covered with the Natural-Y foam, and a smooth silicone control. Materials were placed subcutaneously into the backs of male Lew/SsN rats (n = 81) for 3, 7, 14, and 28 days and 3, 6, and 12 months. Implants were then harvested with their soft-tissue response and evaluated histologically. Analysis demonstrates that microstructuring of a surface, as opposed to a smooth material, will dramatically alter the early, intermediate, and late wound-healing events. The soft-tissue response was observed to be dependent on implant site, material chemistry, and morphology as characterized by exudate formation, macrophage invasion, multinucleated giant cell formation, collagen deposition, foam degradation, and angiogenesis.

Animals

Comparative experience with smooth and polyurethane breast implants using the Kaplan-Meier method of survival analysis.

Smooth-walled silicone implants have been widely used in breast surgery. Capsular contracture, causing undesirable firmness and spherical deformity, has been a common problem. Recent studies suggest that polyurethane-covered breast implants are associated with a lower incidence of capsular contracture. The statistical methodology employed in some of these studies, however, may be subject to criticism. Between July of 1984 and June of 1990 (72 months), 427 polyurethane breast implants were used in 279 patients and 439 smooth prostheses were used in 250 patients for a variety of aesthetic and reconstructive procedures. The occurrence of capsular contracture was carefully monitored and then analyzed using the Kaplan-Meier method of survival analysis. This method is particularly well suited to analysis of these types of clinical data because it allows for the fact that contractures occur at varying intervals after surgery and that follow-up of patients is incomplete. The probability of capsular contracture with smooth-walled prostheses was found to be significantly greater than with polyurethane-covered implants in each group of patients studied (p less than 0.05). Other complications occurred at a similar rate regardless of prosthesis type. This study supports the belief that polyurethane breast implants have a lower contracture rate; furthermore, it introduces the Kaplan-Meier method for analyzing the outcome of alternative plastic surgical therapies.

Breast

The biomechanical and histopathologic effects of surface texturing with silicone and polyurethane in tissue implantation and expansion.

There has been considerable interest in determining the effect of morphologic alterations of prosthetic surfaces on capsule response in breast surgery. The purpose of this study was to provide a precise, three-dimensional evaluation of soft-tissue response to surface modifications in both implantation and expansion. Expandable 100-cc prostheses were designed with one of three surfaces: textured silicone (Biocell), standard smooth silicone, or polyurethane (Natural-Y, Meme). A new submuscular implantation site in the rabbit was developed. Each animal randomly received a smooth-surface device on one side and either a textured silicone or polyurethane device on the other. In one group of animals, the prostheses were expanded monthly. Capsular response was evaluated monthly in vivo using standardized techniques as well as biomechanical methods for up to 6 months in the expander group (n = 7 to 16) and 8 months in the implant group (n = 7 to 15). Analysis of biomechanical and histologic data revealed that prosthetic surface morphology can specifically alter capsular response. Polyurethane was the only effective surface in preventing capsular contracture in implantation. In expansion, both textured silicone and polyurethane surfaces resulted in significantly less capsular contracture and less resistance to expansion than comparable smooth-surfaced controls. Statistical comparisons reveal that the biomechanical methods utilized in this study provide the most precise and objective method of defining overall soft-tissue contracture around implanted biomaterials.

Animals

In vitro function and durability assessment of a novel polyurethane heart valve prosthesis.

While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.

Biocompatible Materials

Thermoplastic polyurethanes as insulating materials for long-life cardiac pacing leads.

Historically, the material most widely used for permanent cardiac pacing lead insulation has been silicone elastomer. We have recently evaluated a variety of polyether polyurethanes and found them also to be suitable as insulating materials for cardiac pacing leads. Test results showed that these polyurethanes are extremely tough, hydrolytically very stable, non-toxic, non-carcinogenic, and very inert in a biological environment. In addition, because polyurethane has a higher tensile strength than silicone elastomer, a thinner insulating layer can be used to construct smaller diameter leads. This facilitates the introduction of one or two leads through small veins or split sheath introducers. The smooth polyurethane material is also very easy to advance through the venous circulation, thus improving the handling characteristics of the lead or leads.

Animals

Long-term performance of polyurethane pacing leads: mechanisms of design-related failures.

Environmental stress cracking has been identified as a crack propagating mechanism in polyurethane-insulated, heart pacemaker leads, which is directly related to specific lead design parameters. Lead designs imposing excessive stress on the polyurethane insulation through an interference fit between the coil and polymer have demonstrated insulation failures. Conversely, low-stress designs have shown virtually no insulation problems. The higher-stress designs have used organic solvents to facilitate coil placement during manufacturing, which may result in lowering the polymer's ability to resist the higher stress. In addition, a specific silver-containing coil wire composition has been found to galvanically corrode upon body fluid intrusion into the lead, ionizing the silver. These ions interact with the polyurethane polymer resulting in the loss of polymer strength. All polyurethane lead failures to date have been specific to high stress and/or chemical interaction. Leads using low-stress designs and nonreactive coil wire compositions continue to demonstrate a positive clinical experience.

Animals