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Synthesis, characterization and platelet adhesion studies of novel ion-containing aliphatic polyurethanes.

Two novel ion-containing aliphatic polyurethanes based on 4,4'-methylene dicyclohexyl diisocyanate (H12MDI), polytetramethyl oxide (PTMO) were synthesized using either sulfonated or carboxylated chain extender. The nonionic polyurethane chain extended with 1,4-butanediol, which is denoted as H-M-BD, was synthesized. Pellethane, a biomedical-grade polyurethane, was also studied for comparison. The polymer's bulk, surface, and platelet-contacting properties were studied using Fourier transform infrared spectrophotometry, differential scanning calorimetry, water absorption analysis, electron spectroscopy for chemical analysis, static contact angle analysis, and in vitro platelet adhesion experiments. The effects of ion incorporation on the morphology, surface properties and blood compatibility are discussed. Unlike MDI-based Pellethane, all H12MDI-based polyurethanes are not composed of crystalline hard segment domain but are amorphous. The ionic polyurethanes exhibit a smaller fraction of hydrogen-bonded carbonyl groups, poorer phase separation, smaller fraction of PTMO residing at the surface, and smaller contact angle; however, significant higher water absorption value than H-M-BD and Pellethane. The in vitro platelet adhesion experiments indicated that ion incorporation, especially for carboxylate, significantly reduced the number and the degree of activation of the adherent platelets.

Absorption↗

Comparison of the effect of a collagen dressing and a polyurethane dressing on the healing of split thickness skin graft (STSG) donor sites.

Recent advances in the resurfacing of burn wounds with dermal equivalents and collagen preparations have shown the efficacy of collagen. To investigate the benefits (if any), standardised split skin donor areas were chosen to compare the influence of collagen on re-epithelialisation. A bovine collagen preparation consisting of type-I collagen was prospectively compared with polyurethane film dressing in a study of 20 split thickness skin graft donor sites. The rates of epithelialisation, the discomfort experienced by the patients and the convenience of the dressings were assessed. The median time from operation to the observation of complete healing was 7.5 (+/- 2.5) days for the donor sites dressed with the collagen membrane and 12.5 (+/- 3.4) days for the the donor areas dressed with a polyurethane film (p < 0.001). The discomfort experienced by the two groups of patients was significantly less after wound coverage with collagen (p < 0.005). Haematomas or seromas that required repeated aspiration was seen under the polyurethane film dressing. The collagen dressing was more expensive than the polyurethane film, but improved wound healing compared with the polyurethane dressings.

Collagen↗

Degradation of dimethylphthalate by cells of Bacillus sp. immobilized in calcium alginate and polyurethane foam.

A Bacillus sp. which is capable of degrading dimethylphthalate (DMP) was immobilized in calcium alginate and polyurethane foam for efficient and long term degradation of DMP. Freely suspended cells (10(12) cfu ml-1) degraded a maximum of 20 mM DMP. Whereas, alginate-(10(12)cfu g-1 beads) and polyurethane foam-entrapped (0.34 x 10(6-9) cfu g-1 foam cubes) cells degraded a maximum of 40 mM DMP within 12-15 days of incubation. Polyurethane foam-entrapped cells degraded 30 mM of DMP at 4 days and alginate-entrapped cells degraded within 10 to 12 days of incubation irrespective of the cell population. When the initial concentration of DMP increased to 50 mM, the DMP degrading ability of the immobilized cells was not increased even after 20 days. Repeated batch cultures by alginate-entrapped cells with initial 35 mM DMP loading could be reused for a maximum of 20 cycles. However, the degradation rate was gradually decreased when the beads were reused for more than 15 cycles. On the other hand, the foam-entrapped cells, with the same initial DMP loading there was no decrease in DMP degrading ability and could be reused for more than 20 cycles. The packed bed reactor with alginate-entrapped cells (1 x 10(10-12) cfu g-1 bead) could be continuously operated for 7-8 days with an initial 25 mM DMP at a flow rate of 50 ml h-1. Whereas, the polyurethane foam-entrapped cells (1 x 10(6-9) cfu g-1 foam cubes) could be operated continuously for more than 90 days with the same initial DMP loading at a flow rate of 100 ml h-1. Thus the enhanced degradation of DMP could be achieved by immobilizing the cells of Bacillus sp. in calcium alginate and polyurethane foam as compared to that of freely suspended cells.

Alginates↗

Biodegradation of polyurethane foam, revisited, in the rat model.

In a prospective, randomized, controlled animal study, we systematically analyzed implanted polyurethane foam to determine the rate of degradation in the rat and to compare it to our previous human data. Sixteen 1-cm2 silicone-backed pieces of polyurethane foam were randomly implanted into dorsal subcutaneous pockets in each of 16 Sprague-Dawley rats. Eight animals had polyurethane implants removed at 3 and 6 months and the remaining 8 animals at 9 and 12 months. Specimens were examined either by histology or by scanning electron microscopy of recovered foam after collagenase digestion of the capsule. Histologically, there was evidence of foam degradation and a multinucleated giant cell inflammatory response surrounding the implants. With the scanning electron microscope, the strut width of the polyurethane foam upon implantation measured 51.4 +/- 1.3 microns (mean+SEM). This progressively decreased to 29.1 +/- 1.3 microns at 3 months, 16.6 +/- 0.6 micron at 6 months, 14.9 +/- 0.5 micron at 9 months, and 13.2 +/- 0.3 micron at 12 months (p < 0.0001). Duration of implantation has a significant impact on polyurethane degradation as measured by scanning electron microscopy in the rat animal model. The rate of degradation in the rat is much faster than in our human study, indicating that the rat studies cannot be used to draw conclusions regarding rate of biodegradation in humans.

Animals↗

Polyurethane real-size models used in planning complex spinal surgery.

STUDY DESIGN: The application of polyurethane real-size models for planning and performing complex spinal surgery is described. OBJECTIVE: To determine the feasibility of using polyurethane real-size models to plan osteotomies, resections, and designs of custom-made spinal implants in complex spinal surgery. SUMMARY OF BACKGROUND DATA: In selected patients with complex spinal pathology, exact planning of the surgical procedure is not possible using current imaging methods. In these cases, real-size spinal models would be desirable to enhance pre- and perioperative planning by visual and tactile feedback, and to improve the production of custom-made spinal implants. METHODS: A real-size spinal model of six patients was produced from hardened polyurethane foam on the basis of data from contiguous computer tomography slices. In two patients, the models were used to plan correction osteotomies and resections, with the assistance of image-guided surgery in one of the patients. In four patients, the models were used to plan tumor resections and to produce custom-made spinal implants. RESULTS: In all the patients, the surgical procedure could be performed exactly according to the preplanned intervention. The polyurethane real-size models provided essential and additional information by direct visual and tactile feedback. They allowed in vitro testing of custom-made spinal implants with a perfect fit. CONCLUSIONS: Real-size spinal models made from polyurethane foam can be used to provide excellent understanding of the complex spinal pathology in highly selected patients. These models allow complex spinal surgery with a more predictable outcome.

Adolescent↗

Isocyanates, polyurethane and childhood asthma.

Isocyanates are the most prominent and well-studied cause of occupational asthma. Over the decades, airborne isocyanates have been regulated to extremely low levels in the workplace, some of the lowest for any organic compound. Yet the incidence of isocyanate-induced occupational asthma remains high and the role of dermal exposure in disease etiology is only slowly being recognized. Almost completely overlooked is the potential relationship between isocyanates in consumer products and increasing prevalence of asthma in the general population, especially children. The steady rise in asthma over the past decades points strongly to a potential role of environmental exposures in its development. Imbalances in the immune system favoring respiratory diseases have been linked to biological and chemical stressor exposures early in life. Evidence for the presence of isocyanates in many polyurethane-containing materials, especially polyurethane foams, is presented as a possible contributor to the increase in asthma. Polyurethane foam is ubiquitous in western societies and used in bedding, furniture, automobile seats, footwear, etc., and numerous medical materials. Theoretical, epidemiologic, experimental and clinical evidence of a role for isocyanates and polyurethanes in the genesis of non-occupational allergy and respiratory disease are reviewed. These data all point to the urgent need for additional research on the links between isocyanates, polyurethanes and the role of the skin in non-occupational asthma.

Adult↗

Long-term comparison of the electrical characteristics of polyurethane and polyethylene insulated ventricular leads.

Two types of pacing leads with different insulation material, polyurethane, and polyethylene, were followed for 44 months with respect to their electrophysiological characteristics and complications. In 48 patients, 32 polyurethane leads (Lifeline 493-03) and 16 polyethylene leads (EMT 588 D) were implanted and connected in all cases to the same type of programmable ventricular inhibited (VVI) pulse generator (Programalith, Pacesetter). There was a significant fall during the follow-up in lead impedance with the polyurethane leads (495 +/- 62 to 444 +/- 58 ohms, P less than 0.01), whereas the corresponding measurements for the polyethylene leads were essentially unchanged (360 +/- 58 to 378 +/- 71 ohm, ns). The energy of the stimulation threshold tended to increase in the polyurethane group, whereas an opposite tendency was observed in the polyethylene group. Pacing and/or lead failures were not observed in any case. The observed fall in impedance with the polyurethane leads was seemingly of no clinical significance.

Aged↗

Polyethylene terephthalate and polyurethane coatings for endovascular stents: preliminary results in canine experimental arteriovenous fistulas.

PURPOSE: To evaluate polyethylene terephthalate and polyurethane as coatings of vascular endoprostheses in the treatment of experimental arteriovenous fistulas (AVFs). MATERIALS AND METHODS: Nineteen bilateral carotid artery-to-external jugular vein AVFs were created in 10 adult dogs. Fourteen polyethylene terephthalate-coated and five polyurethane-coated self-expandable nitinol stents were placed with a transfemoral approach. Angiography was performed immediately after placement, after 1 and 3 weeks, and at months 3, 6, 9, and 12. All grafts were examined histopathologically. RESULTS: The AVF was successfully occluded with all but one of the polyethylene terephthalate-coated stents. Graft patency was seen with 12 polyethylene terephthalate-coated stents, while acute vessel occlusion was evident with two polyethylene terephthalate-coated stents following percutaneous transluminal angioplasty immediately after implantation. In the group with polyurethane-coated stents, three graft dislocations and two delayed vessel occlusions were observed. In both groups, histologic examination disclosed a mild foreign body reaction with a few macro-phages. No inflammatory reactions were seen. An unorganized fibrin layer was found adjacent to the polyurethane coating. CONCLUSION: Polyethylene terephthalate-coated nitinol stents showed good biocompatibility and a high rate of occlusion of experimental AVFs. The mechanical properties of the polyethylene terephthalate coating were similar to those of the nitinol stents, which facilitated handling. Polyurethane-coated stents showed frequent dislocation.

Alloys↗

High density culturing of porcine hepatocytes immobilized on nonwoven polyurethane-based biomatrices.

OBJECTIVE: Hepatocytes are increasingly used as functional units in bioartificial liver devices. The objective of the present study was to investigate the feasibility of culturing porcine hepatocytes in high density on a novel polyurethane-based nonwoven three-dimensional matrix. We investigated (1) the optimal cell density within this culture configuration, (2) the maintenance of liver-specific morphology and cell functions over long-term periods and (3) the necessity to apply an additional extracellular matrix component (collagen gel). METHODS: Nonwoven polyurethane matrices were manufactured by a specially developed fiber extrusion technology. Pig hepatocytes were cultured at various cell densities of 0.1, 0.25, 0.5, 0.75, 1 and 2 x 10(6) cells/cm(2) on three-dimensional networks of nonwoven polyurethane matrices and cell adhesion as well as functional parameters (DNA of nonattached/attached cells, lactate dehydrogenase release and cytochrome P450 activity) were determined. To assess the performance of cells within this configuration albumin and urea excretion was measured over 8 days. The potentially beneficial effect of an additional extracellular matrix configuration was evaluated by comparing the average albumin synthesis in groups of identical cell numbers. RESULTS: The optimal cell density in this three-dimensional culture configuration was 1 x 10(6) cells/cm(2). The functional capacity of hepatocytes was stable for 8 days at an average level of 53.7 +/- 5.6 ng/h/microg DNA and of 1.8 +/- 0.14 microg/h/microg DNA for albumin and urea excretion, respectively. The supplementation of an extracellular matrix configuration did not improve functional activity of cells. Average albumin synthesis was 35.6 ng/h/microg DNA (28.7, 42.8) and 32.7 ng/h/microg DNA (23.4, 49.2) for collagen-immobilized and control cultures, respectively. CONCLUSION: The results of the study indicate that nonwoven polyurethane sheets supply a biocompatible support structure for functionally active high density cultures. Thus, nonwoven polyurethane matrices should be further investigated on with respect to their role in the development, optimization and design of bioartificial liver systems.

Animals↗

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) soft segment.

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) glycol (HPIP) and 4,4'-methylendiphenyl diisocyanate (MDI) was synthesized using 2-[bis(2-hydroxyethyl)methyl-ammonio]ethylstearylphosphate (BESP) and 1,4-butanediol (BD) as chain extender. The bulk and surface characteristics of this material was investigated by differential scanning calorimetry (DSC), dynamic viscoelasticity and tensile property measurements, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurement. This polymer possessed a hydrophobic surface revealed by contact angle measurement. The haemocompatibility of this polyurethane was evaluated by platelet rich plasma (PRP) contacting studies and scanning electron microscopy (SEM) observation using medical grade poly(vinyl chloride) (PVC) as the reference. The results show that this new polyurethane had relatively lower platelet adhesion and limited shape change for the attached platelets compared to PVC. The clotting time of the materials in contact with platelet poor plasma (PPP) was 99, 75, and 62 s and in contact with PRP was more than 240, 100, and 86 s for new polyurethane, PVC, and glass, respectively. This new phospholipid polyurethane is expected to have wide applications as coating or structural material for blood-contacting medical equipment due to its outstanding haemocompatibility and excellent mechanical strength.

Biocompatible Materials↗

Bacterial adhesion to polyurethane surfaces in the presence of pre-adsorbed high molecular weight kininogen.

The factors which affect the adherence of a bacteria cell to the surface of a biomaterial include the surface chemistry of the cell and material, as well as the composition of the adsorbed protein layer when the biomaterial is exposed to circulating blood. In an effort to better understand the mechanisms by which bacteria adhere to such surfaces, and specifically to determine the effects of high molecular weight kininogen on bacterial adhesion, experiments were performed in which the attachment of Staphylococcus aureus was directly observed on glass and on a series of functionalized polyurethanes. These surfaces had been pre-adsorbed with various concentrations of high molecular weight kininogen and fibrinogen. Attachment was observed using a radial flow chamber, in which shear stress varied inversely with radial distance. Protein adsorption studies were also performed using 125I labeled fibrinogen to investigate the relationship between surface chemistry, protein adsorption, and bacterial attachment. Bacterial attachment was significantly decreased when the glass surface was pre-adsorbed with high molecular weight kininogen--either alone, or following adsorption of fibrinogen. High molecular weight kininogen thus exhibited anti-adhesive effects. On polyurethane surfaces pre-adsorbed with fibrinogen, kininogen, and albumin, the highest bacterial attachment was found on the base polyurethane, while significant decreases were seen on the hydrophilic polyurethanes. In addition, it was found that the surface with the least bacterial attachment and fibrinogen deposition was the polyurethane with pendant phosphonate groups.

Adsorption↗

Comparison between polyurethanes containing castor oil (soft segment) and cancellous bone autograft in the treatment of segmental bone defect induced in rabbits.

The aim of this study is to compare polyurethanes containing castor oil (soft segment) in granular form compared to cancellous bone autograft applied to a segmental bone defect. Norfolk adult female rabbits - approximately 13 months of age with a mean body weight of 4.5 kg - are used. In both radial diaphyses, 1 cm osteoperiosteal segmental defects are created. The defect in the left radius is filled with the castor-oil-based polyurethane, and the right one, filled with cancellous bone autograft, collected from the left proximal humerus. The rabbits are euthanazed at 15, 30, 60, and 120 days postsurgery (5 animals/ period), for histological analyses. By radiographic analyses, at these time points, the bone regeneration is more evident and accelerated in the bone defects treated with the cancellous bone autograft. At 120 days postsurgery, the segmental bone defects treated with the cancellous bone autograft are totally reconstituted and remodeled, while the bone defects treated with polyurethane polymer have bone formation of 79%. Histological study shows that the polyurethane acts as a space filler, minimizing the local production of fibrous tissue. No granule degradation, resorption or any inflammatory reaction is detected. Thus, it is possible to conclude that the castor-oil-plant-based polyurethane - in the granule presentation - is biocompatible and osteointegrated, but does not show the same bone regeneration capacity as the cancellous bone autograft.

Animals↗

Factors and interactions affecting the performance of polyurethane elastomers in medical devices.

Polyurethanes offer the greatest versatility in compositions and properties of any family of polymers. For implantable medical devices, a few specific elastomeric polyurethane compositions have demonstrated a combination of toughness, durability, biocompatibility and biostability not achieved by any other available material. Because of the complex behavior of implantable polyurethanes in the body environment, designers and fabricators of polyurethane-containing devices must pay particular attention to the choice of composition and design of components. Subsequent treatment during qualification, fabrication, sterilization, storage, implantation, in vivo operation and explantation also determine the performance and provide the means for assessing the efficacy of the polyurethane in the implanted device.

Biocompatible Materials↗

The use of silicone/polyurethane graft polymers as a means of eliminating surface cracking of polyurethane prostheses.

The long-term biodegradation of various polyurethanes with and without surface modifications was evaluated by implanting small porous filamentous patches of these materials subcutaneously in the backs of dogs for one month. Data were compared to those obtained with spun polyurethane vascular grafts of similar materials implanted in the aorto-iliac position in dogs. The extremely high surface area of approximately 7 m2/cm3 of these porous filamentous patches provided numerous sites for surface cracking and the very fine filaments (10 microns in diameter) provided an easily identifiable structure to study the cracking phenomenon. Results from numerous one month implants clearly demonstrated that the subcutaneous implant model effectively reproduced the biodegradation behavior observed in vascular graft implants. The degradation was most pronounced in the softer Shore 80A polyurethanes and less pronounced in the harder 55D and 75D polyurethanes. The degradation could not simply be stopped by stress annealing the polyurethane and the degradation did not require the presence of metallic ions. Antioxidants, surface adsorbed albumin, poly(2-hydroxyethyl-methacrylate) grafting, silicone copolymerization, tetrafluoroethylene plasma discharge and the addition of urea linkages to the polymer were also shown to be ineffective in stopping the biodegradation process. In contrast, covalent bonding or grafting of silicone polymer to the surface of the urethane successfully inhibited the biodegradation process.

Animals↗

Polyurethane elastomer biostability.

Polyurethanes have unique mechanical and biologic properties that make them ideal for many implantable devices. They are subject to some in vivo degradation mechanisms, however. Polyester polyurethanes are subject to hydrolytic degradation and are no longer used in long-term implanted devices. Polyether polyurethanes, while hydrolytically stable, are subject to oxidative degradation in several forms, including environmental stress cracking and metal ion oxidation. Mineralization is also known to occur. A new polycarbonate polyurethane has superior biostability in early in vivo qualification tests compared to the polyether polyurethanes, including no evidence of hydrolysis, ESC or MIO.

Animals↗

Biomedical applications of polyurethanes: a review of past promises, present realities, and a vibrant future.

Polyurethanes, having extensive structure/property diversity, are one of the most bio- and blood-compatible materials known today. These materials played a major role in the development of many medical devices ranging from catheters to total artificial heart. Properties such as durability, elasticity, elastomer-like character, fatigue resistance, compliance, and acceptance or tolerance in the body during the healing, became often associated with polyurethanes. Furthermore, propensity for bulk and surface modification via hydrophilic/hydrophobic balance or by attachments of biologically active species such as anticoagulants or biorecognizable groups are possible via chemical groups typical for polyurethane structure. These modifications are designed to mediate and enhance the acceptance and healing of the device or implant. Many innovative processing technologies are used to fabricate functional devices, feeling and often behaving like natural tissue. The hydrolytically unstable polyester polyurethanes were replaced by more resistant but oxidation-sensitive polyether polyols based polyurethanes and their clones containing silicone and other modifying polymeric intermediates. Chronic in vivo instability, however, observed on prolonged implantation, became a major roadblock for many applications. Presently, utilization of more oxidation resistant polycarbonate polyols as soft segments, in combination with antioxidants such as Vitamin E, offer materials which can endure in the body for several years. The applications cover cardiovascular devices, artificial organs, tissue replacement and augmentation, performance enhancing coatings and many others. In situ polymerized, cross-linked systems could extend this biodurability even further. The future will expand this field by revisiting chemically-controlled biodegradation, in combination with a mini-version of RIM technology and minimally invasive surgical procedures, to form, in vivo, a scaffold, by delivery of reacting materials to the specific site in the body and polymerizing the mass in situ. This scaffold will provide anchor for tissue regeneration via cell attachment, proliferation, control of inflammation, and healing.

Animals↗

Estimation of organophosphoric acid triesters in soft polyurethane foam using a concentrated sulfuric acid dissolution technique and gas chromatography with flame photometric detection.

A concentrated sulfuric acid dissolution technique and a GC method are described for the estimation of tributyl phosphate, tris(2-chloroethyl) phosphate, tris(chloropropyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, triphenyl phosphate and tris(butoxyethyl) phosphate in soft polyurethane foam. A soft polyurethane foam sample containing organophosphoric acid triesters was dissolved in concentrated sulfuric acid. The solution was added to water, where only the polyurethane was separated out. The pH of the solution was adjusted, and organophosphoric acid triesters were extracted with toluene. After purification, the compounds were determined by GC. The detection limits of the organophosphoric acid triesters were 0.3 - 0.9 microg g(-1). The recoveries of the organophosphoric acid triesters from a 0.05 g sample of soft polyurethane foam were 80.0 - 90.0%, when the spiked amounts were 0.25 - 1 microg. The compounds were detected from soft polyurethane foam at the level of 0.4 - 23.3 microg g(-1).

Chemical Fractionation↗

Subchronic 10 day immunotoxicity of polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice.

Millions of people have been exposed to silicones because of the widespread use in consumer products such as cosmetics and toiletries, food products, household products and paints. Silicones have wide use in medical practice, including lubricants in tubing and syringes, and as implantable devices. The most prevalent silicone in medical use is polydimethylsiloxane. This study was undertaken to determine the subchronic immunotoxicologic potential of the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones did not alter the distribution of B cells and T cells in the spleen, but polyurethane perturbed the distribution of CD4+CD8+ and CD4-CD8- T cells. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, but polyurethane evoked an enhanced phagocytosis of Covaspheres by adherent peritoneal cells. Natural killer cell activity and serum complement were not altered. All silicone materials afforded modest protection to a challenge with Listeria monocytogenes that killed 40 to 58% of control mice. Host resistance to Streptococcus pneumoniae or the B16F10 tumor was not affected by any of the treatments. There is a pattern indicative of some perturbation of T cell differentiation in mice implanted with a polyurethane disk.

Animals↗