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Reduced platelet adhesion on the surface of polyurethane bearing structure of sulfobetaine.

Poly(etherurethane)s are widely used as blood-contacting biomaterials due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for the more demanding applications. Surface modification is an effective way to improve the blood compatibility and retain the bulk properties of biomaterials. The purpose of present study was to design and synthesize a novel nonthrombogenic biomaterial by modifying the surface of poly(etherurethane) with zwitterionic monomer. Films of polyurethane were grafted with sulfobetaine by a three-step procedure. In the first step, the film surfaces were treated with hexamethylene diisocyanate (HDI) in toluene at 50 degrees C in the presence of di-n-butyl tin dilaurate (DBTDL) as a catalyst. The extent of the reaction was measured by ATR-IR spectra; a maximum number of free NCO group was obtained after a reaction time of 90 min. In the second step, the hydroxyl group of 4-dimethylamino-1-butanol (DMAB) was allowed to react in toluene with isocyanate groups bound on the surface. In the third step, sulfobetaine was formed on the surface through the ring-opening reaction between tertiary amine of DMAB and 1,3- propane-sultone (PS). It was characterized by ATR-IR, XPS. The data showed that the grafted surfaces were composed of sulfobetaine. The results of the contact angle measurements showed that they were strongly hydrophilic. The state of platelet adhesion and shape variation for the attached platelets was described. The modified surface shows excellent blood compatibility feature by the low platelet adhesion.

Betaine↗

In vitro interactions of biomedical polyurethanes with macrophages and bacterial cells.

Three commercial medical-grade polyurethanes (PUs), a poly-ether-urethane (Pellethane), and two poly-carbonate-urethanes, the one aromatic (Bionate) and the other aliphatic (Chronoflex), were tested for macrophages and bacterial cells adhesion, in the presence or absence of adhesive plasma proteins. All the experiments were carried out on PUs films obtained by solvent casting. The wettability of these films was analysed by measuring static contact angles against water. The ability of the selected PUs to adsorb human fibronectin (Fn) and fibrinogen (Fbg) was checked by ELISA with biotin-labelled proteins. All PUs were able to adsorb Fn and Fbg (Fn > Fbg). Fn adsorption was in the order: Pellethane > Chronoflex > Bionate, the highest Fbg adsorption being detected onto Bionate (Bionate > Chronoflex > Pellethane). The human macrophagic line J111, and the two main bacterial strains responsible for infection in humans (Staphylococcus aureus Newman and Staphylococcus epidermidis 14852) were incubated in turn with the three PUs, uncoated or coated with plasma proteins. No macrophage or bacterial adhesion was observed onto uncoated PUs. PUs coated with plasma, Fn or Fbg promoted bacterial adhesion (S. aureus > S. epidermidis), whereas macrophage adhered more onto PUs coated with Fn or plasma. The coating with Fbg did not promote cell adhesion. Pellethane showed the highest macrophage activation (i.e. spreading), followed, in the order, by Bionate and Chronoflex.

Biotin↗

Synthesis, physical properties and preliminary investigation of hemocompatibility of polyurethanes from aliphatic resources with castor oil participation.

The synthesis of polyurethanes (PURs) from oligoetherdiol, two low molecular diols, castor oil and 4,4'-Methylenebis(cyclohexylisocyanate) is described. These polymers are characterized by measurements of the mechanical bulk and surface properties, preliminary investigation of compatibility with human blood and calcification in static conditions. The critical surface energy of synthesized PURs is similar to the critical surface energy of natural surfaces. Material-induced hemolysis and the changes of platelet counts in blood samples after contact with PURs are very low. Static seven-weeks-calcification testing in a synthetic calcification fluid did not indicate calcification by optical density measurements and by visual inspection and computer image processing of the X-ray films for PURs with and without castor oil.

Biocompatible Materials↗

In vitro biocompatibility of PTMO-based polyurethanes and those containing PDMS blocks.

In this work, a series of different polyurethanes based on poly(tetramethylene oxide) (PTMO, MW approximately 2000) and chain extended with butenediol were synthesized by a two-step solution polymerization. Three of them contained silanol terminated polydimethylsiloxane (PDMS, MW approximately 2000) blocks. It was shown that these polymers exhibited various degrees of micro-phase separation that further influenced their biological performances in vitro. The formulation with diphenylmethane diisocyanate/PTMO/PDMS/2-butene-1,4-diol at a molar ratio of 2: 0.75: 0.5: 1 in synthesis was favorable due to a combination of enhanced mechanical properties, biostability, cellular affinity as well as platelet nonadherence.

Biocompatible Materials↗

Blood compatible polyurethane elastomers.

Medical applications of blood compatible polyurethane elastomers contribute significantly to the quality and effectiveness of the nation's health system. These projects range from artificial hearts to diagnostic/therapeutic cardiac catheters which are saving the lives of many critically ill patients.

Animals↗

Softening of thermoplastic polyurethanes: a structure/property study.

Softening of thermoplastic polyurethanes (TPU) in a simulated body environment (37 degrees C n-saline) was studied as a function of composition, structure and resultant morphology of these (AB)n type block copolymers. The structural variations were attempted by changing chemical composition and molecular weight of both hard A and soft B segments and their weight ratio in the polymer. In addition, the influence of bulk and/or surface modifiers, such as "reacted-in" polysiloxanes and fluorinated polyalkylether glycols, was also investigated. The degree of softening, expressed as a percentage decrease of the elastic modulus (5% tensile modulus) upon two hours exposure to the testing environment, is significant, reversible and depends on the ratio of hard to soft segment and the extent of microphase separation. Since these parameters can be selected during the polymer synthesis and processing into desirable shapes, the degree of softening can thus be controlled. This softening at body temperature represents one of the most notable performance advantages of these biomaterials.

Elasticity↗

Biocompatible polyurethane-based hydrogel.

A polyurethane polymer developed at W. R. Grace has been evaluated for a variety of biomedical applications. The primary property of the polymer exploited for these applications is its ability to prevent protein adsorption when coated on a surface. The prepolymer consists of a trifunctional poly(ethyleneoxide-propylene oxide) triol end capped with isophorone diisocyanate. The prepolymer is reactive with water and can be converted to a hydrogel, a thin coating, or a soluble conjugate with another compound. Each category lends itself to separate biomedical applications which are described in detail. The non-toxic nature of the polymer was demonstrated in a number of systems and suggests its utility in biomedical applications.

Adsorption↗

Formation and elution of toxic compounds from sterilized medical products: methylenedianiline formation in polyurethane.

The formation of a toxic and carcinogenic compound, methylenedianiline (MDA), in sterilized medical use polyurethane (PU) is discussed. Due to good biocompatibility and biostability, PU is widely used for blood-containing devices. There are two types of PU currently available for medical use. One is chain-extended thermoplastic PU, the other is thermosetting PU used for potting material connecting fibers and modules in artificial dialyzers and plasma separators. Both gamma-ray irradiation and autoclave sterilization are predominantly used for the sterilization of these devices. MDA formation in sterilized PUs by gamma-ray irradiation and by autoclave treatment is compared. The Delany clause in the USA prohibits the manufacture of medical devices producing any toxic compound during fabrication and sterilization, therefore, the formation and elution of MDA and other toxic compounds should be seriously considered. Although MDA formation at a concentration of a few to a few hundred ppb in autoclaved chain-extended thermoplastic PU has been reported, there have been no papers describing MDA formation in autoclaved thermosetting PU potting material, or describing MDA formation in gamma-ray irradiated chain-extended thermoplastic PU and thermosetting PU. We elected to determine whether MDA was in fact produced in Pus sterilized by gamma-ray irradiation or by autoclave sterilization. Our objective was to estimate the risk factor to the human patients or recipient. Our conclusion is to confirm which sterilization of gamma-ray or autoclave is more appropriate. No formation of MDA was observed in autoclaved thermosetting PU potting material at 121 degrees C for 60 min. A few ppm of MDA was formed in irradiated potting material. MDA formation increased with increasing irradiation doses. MDA formed in irradiated potting material at 2.5 Mrad (less than one ppm) is not a significant risk to the recipient. The estimated cancer causing risk factor when absorbing one mg MDA/kg body weight/day is 0.29. Twenty-nine persons per 100 persons exhibit a cancer potential. More importantly, our experimental evidence indicated that serum extracts from irradiated potting material contained unknown compounds other than MDA. The presence of these compounds is considerably more significant and toxic. When tested, these compounds proved to be mutagenic in the absence of metabolic activity, thus promoting a need to identify and study further. Compounds indicating mutagenicity increased with increasing irradiation. Small amounts of mutagenic compounds were determined in extract from autoclaved potting material, smaller than that by gamma-ray irradiation. Therefore, autoclave sterilization is more appropriate, providing materials can withstand the process.(ABSTRACT TRUNCATED AT 400 WORDS)

Aniline Compounds↗

[Investigation of the cause of polyurethane catheter cracking during constant infusion of etoposide (VP-16) injection (2)--Analysis of ethanol eluting materials from catheter].

We studied the cause of cracking of clinically used polyurethane (PU) catheters during the constant infusion of etoposide (VP-16) injection (Lastet inj.) without dilution. After the vehicles used for VP-16 injection, ethanol or polyethylene glycol 400 (PEG400), were infused into the PU catheters at a constant infusion rate (30 ml/h) for 24 h, obvious degradation of the internal wall of the catheter was observed under an electron microscope. When the PU catheter was immersed in ethanol for 24 h, condensed polymers of 1,4-butanediol (BD), contained in PU catheters as an elasticizer, were detected in the ethanol elute using the ESI/MS method. Moreover, time-dependent elution of BD from PU catheters with the infusion of ethanol into the catheter for 24 h at 30 ml/h was observed using the GC/MS method. The cumulative amount of BD eluted from the PU catheter with ethanol vehicle for 24 h was 130 micrograms. In conclusion, degradation and subsequent cracking of PU catheters during the infusion of VP-16 injection were caused by ethanol and PEG400 contained in the injection solution. Furthermore, to prevent the elution of BD from PU catheters, we suggest that PU catheters should not be used for the administration of VP-16 injection without dilution in consideration of safety and efficacy.

Butylene Glycols↗

[The cause of polyurethane catheter cracking during constant infusion of etoposide (VP-16) injection].

We studied the cause of cracking of a clinically used polyurethane (PU) catheter during the constant infusion of etoposide (VP-16) injection (Lastet), administered without dilution to patients as a part of combination high-dose chemotherapy. After VP-16 injection was infused into the PU catheter at a constant infusion rate (30 ml/h) for 24 h, a decrease in the elasticity (36% of untreated) and on increase in the length of the catheter (3.7%) were observed. These changes were significantly higher than those treated with the control saline. The similar changes of the PU catheter were observed after treatment with a basal solution containing polyethylene glycol 400 (PEG 400), polysorbate 80 and ethanol, which is the vehicle of the VP-16 injection, and with ethanol alone. Moreover, obvious degeneration of the internal wall (occurrence of spots like melting) and cutting face (micro-cracking) of the catheter was observed with an electron microscope after treatment with the vehicle. On the other hand, the elasticity or extension of the PU catheter were not changed after treatment with saline or PEG 400. From these findings, it was suggested that the degeneration and subsequent cracking of the PU catheter during the infusion of VP-16 injection was caused by ethanol contained in its injection solution. No cracking or morphological changes of polyvinyl chloride (PVC) and silicone catheters were found after treatment with the vehicle solution. However, since it has been reported in previous reports that di(2-ethylhexyl)phthalate was leached from PVC bags, the high dose chemotherapy with the dilution-free VP-16 injection should be achieved safely and effectively using a silicon catheter, rather than the PU catheter.

Antineoplastic Agents, Phytogenic↗

Reconstruction of large fronto-orbital defects with Dacron polyurethane custom prosthesis and autogenous bone.

Reconstruction of large defects of the frontal bone and bony orbit may be required following trauma or ablative tumor surgery. Autogenous bone or alloplastic implants used alone may prove inadequate due to difficulties obtaining symmetric contours with bone and lack of strength and resistance to infection with alloplastic materials. These problems can be overcome with the combined use of a prefabricated Dacron polyurethane mesh prosthesis (Osteo-Mesh, Xomed, Inc.) to establish contour of the forehead and superciliary ridges, and underlying split-rib grafts to protect the brain and isolate the paranasal sinuses. This technique is not indicated for small frontal defects, but it should be considered for use by the head and neck surgeon who is faced with the challenge of reconstructing a major fronto-orbital defect.

Adult↗

Pulmonary response to polyurethane dust.

Weanling and 9 months or older rats were exposed to particles of an aged (PUF I) or freshly prepared (PUF II) rigid polyurethane foam by intratracheal intubation. The dose was 5 mg of particles. The response of the lung tissue was examined morphologically by serial sacrifices. Inflammation and macrophage activity were the initial responses. Fibrosis developed after 6 months. Nodular scars and perifocal emphysema were seen after 12 months. Four rats had a papillary adenoma in a major bronchus after 18 months exposure to PUF II.

Age Factors↗

Mefilm: an adherent polyurethane dressing for superficial wounds.

Research has demonstrated that wounds heal faster in a moist environment. Film dressings are used to promote a moist environment. Mefilm is part of the Mölnlycke Health Care chronic wound care system and is a gentle, adherent polyurethane dressing. This product focus discusses the development of the semi-permeable film dressing, Mefilm, examining its uses, application and removal.

Humans↗

Evaluation of a new polyurethane foam dressing.

The treatment of moderately to heavily exuding wounds requires a dressing that will remove excess exudate while ensuring optimum conditions at the wound site and preventing maceration of the surrounding skin tissue. This prospective, stratified, randomised clinical trial was designed to assess the performance and safety of a new polyurethane foam dressing compared with a hydrocellular dressing. Both dressings are currently available to community nurses for the treatment of these wound types. Sixty-one patients recruited to the trial. They were grouped according to wound type: 20 leg ulcers, 20 Grade 2 or Grade 3 pressure sores and 21 other wounds that included traumatic, acute and chronic wounds and burns. Patients were randomized to treatment and dressing changes and assessments were undertaken as required. Condition of the wound and surrounding skin, comfort, ease of use and leakage from the dressing were monitored at each assessment. Treatment continued for six weeks or until the wound was lightly exuding (defined as absence of leakage with the dressing remaining in place for more than four days on two consecutive occasions). Photographs and tracings of the wounds were taken weekly. The results showed that the two dressings were similar in performance in that they could remain in place for approximately 2.5 days, irrespective of wound type. There were no statistically significant differences in surrounding skin condition, reduction in wound size, patient comfort or ease of application and removal.

Aged↗

Treating hypertrophic scars for 12 or 24 hours with a self-adhesive hydroactive polyurethane dressing.

Treatment with a self-adhesive hydroactive polyurethane dressing (Cutinova thin, Beiersdorf AG, Hamburg, Germany) applied over a period of eight weeks has been shown to have a beneficial effect on hypertrophic scars. However, the use of such dressings during the daytime on visible parts of the body is often problematic and might lead to reduced compliance. In the present study the effect of 12-hour (overnight) treatment was compared with the results of a 24-hour treatment regimen with the same dressing. The dressings were applied over an eight-week period. Evaluation of the hypertrophic scars was by clinical assessment and measurement of colour difference to normal skin, elevation and elasticity. In addition, the patients assessed the treatment effects (questionnaire) and photographs were taken. Under both regimens an improvement in the scar colour (redness) and visual assessment scores took place. The patients also gave a positive assessment of the effects of the treatment. After eight weeks there were no relevant differences between the scars treated with the self-adhesive dressings for 12 hours (overnight) and those treated for 24 hours per day.

Adhesives↗

Reactive oxygen species, cell growth, and taxol production of Taxus cuspidata cells immobilized on polyurethane foam.

Dynamic changes in reactive oxygen species (ROS) of Taxus cuspidata cells immobilized on polyurethane foam were investigated and the relation between ROS content and taxol production was discussed. Immobilization shortened the lag period of cell growth and moderately increased H2O2 and O2-* contents inside the microenvironment within the first 15 d. After 20 d, excessive production of H2O2 and O2-* was observed accompanied by marked increases in membrane lipid peroxidation and cell membrane permeability. The taxol content of immobilized cells was fourfold that of suspended cells at d 35. The addition of exogenous H2O2 barely affected malondialdehyde content and cell membrane permeability but led to an obvious accumulation of taxol. It is inferred that the intracellular and extracellular H2O2 inside the microenvironment might be one factor promoting taxol biosynthesis under the immobilization stress.

Cell Culture Techniques↗

Immobilized catalase on CoFoam hydrophilic polyurethane composite.

Catalase from bovine liver was covalently immobilized on hydrophilic polyurethane composite (CoFoam). The activity of the enzyme was assayed in the decomposition of H2O2 at pH 7.0 and 25 degrees C. The effects of water-to-prepolymer ratio, the addition of a crosslinking agent, and the utilization of a spacer on enzyme activity were examined. The results of immobilization of the enzyme in a large-scale unit are reported. The advantage of the CoFoam composite lies in the low drop in pressure in a packed-bed reactor at fairly large flow rates. For example, at flow rates of 10-12 L/min, the drop in pressure is typically 3 kPa. Enzymes immobilized on CoFoam represent a novel use as catalysts in packed-bed reactors owing to the low drop in pressure.

Animals↗

Cellular proliferation, differentiation and apoptosis in polyether-polyurethane sponge implant model in mice.

The integration of implanted material to host organism requires spatial and temporal organization of several cellular processes, such as proliferation, differentiation and apoptosis. Despite the clinical relevance of these processes, there is little information regarding the sequence of such events in synthetic matrices. Here, we present a combination of techniques used to characterize the fibrovascular response in subcutaneous polyether-polyurethane sponge implants in mice at days 4, 7, 10 and 14 postimplantation. The AgNOR technique was modified and used as a surrogate marker for proliferating and activated cells invading the implant. The number of AgNOR-stained cells increased progressively from day 4 (606+/-76) to day 14 (2146+/-71) postimplantation. The number of TUNEL-positive (apoptotic index) cells also increased progressively from day 4 (459+/-40) to day 14 (1157+/-119) postimplantation. However, the ratio of TUNEL-labeled/proliferating cells had its highest peak in the early phase of the process remaining stable until day 14. Using Picrosirius staining it was shown that thin collagen increased from day 4, peaking at day 10 and falling markedly at day 14, whereas dense collagen increased progressively during the whole period. These experiments hold potential to investigate not only distinct phases of tissue repair induced by synthetic matrices but also to study underlying mechanisms involved.

Animals↗