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Preparation and surface properties of PEO-sulfonate grafted polyurethanes for enhanced blood compatibility.

In order to improve the thromboresistance of the commercial polyurethane(PU), its surface modification was accomplished by three new different methods and their surface characteristics were investigated using ATR-FTIR, ESCA, SEM, and dynamic contact angle measurements. Sulfonations using propane sultone were performed directly onto PU or onto hydrophobic dodecanediol (DDO) grafted PU or onto hydrophilic poly(ethyleneoxide) (PEO) grafted PU. ESCA data coincided well with ATR-IR results, as more 0 at. % for PEO grafted PUs and the presence of S for the sulfonated PUs were revealed. At SEM observation the surfaces of PU-DDO and PU-PEO were relatively smooth, whereas all the sulfonated PU surfaces showed excellent smoothness and homogeneity. The hydrophilicity of the surfaces was considerably increased after PEO grafting or sulfonation. In addition, all the sulfonated PU surfaces, particularly PU-PEO-SO3, which has further hydrophilicity, exhibited complete wetting behavior due to the negatively charged SO3 groups.

Alkanesulfonates↗

In vitro leukocyte adhesion to modified polyurethane surfaces: III. Effect of flow, fluid medium, and platelets on PMN adhesion.

The operation of filters used to remove leukocytes from red cell concentrates may depend on the adhesion and mechanical trapping of leukocytes. If adhesion is a major component of filtration then filter materials which augment leukocyte adhesion will be useful. In previous leukocyte adhesion studies, done without flow, poly(ethyleneimene) (PEI) modified polyurethane (PU) films were shown to have greater adhesion when compared with unmodified PU. Since filtration is done under flow conditions, it was decided to study PMN adhesion at a number of flow rates using an established parallel plate flow cell. The influence of divalent cations, plasma and platelets were investigated in the presence of red cells, 40% Hematocrit. The number of adherent PMNs to the PEI modified films was always substantially higher than that for the unmodified ones when the shear rate was set at 30 s-1. When using Tyrode's solution containing albumin, with or without divalent cations, a maximum in PMN adhesion was found between the shear rates of 10 and 100 s-1. With Tyrode's solution containing albumin and with 10% (v/v) plasma in saline, the addition of platelets increased PMN adhesion when divalent cations were absent. Adhesion levels with 10% (v/v) plasma in saline were reduced when compared to Tyrode's solution containing albumin without divalent cations. These results support the use of filtration conditions where the concentration of plasma is reduced and the concentration of divalent cations is increased. Detailed evaluation of filter function with flow rate is also recommended. A cell adhesion promoting polymer coating, such as PEI, may be useful in improving filter efficiency.

Cell Adhesion↗

Antithrombogenicity of hydrophilic polyurethane-hydrophobic polystyrene IPNs. I. Synthesis and characterization.

A series of interpenetrating polymer networks (IPNs) composed of hydrophilic polyurethane (PU) and hydrophobic polystyrene (PS) were prepared by the simultaneous polymerization method. The PU network was synthesized via the isocyanate-terminated PU prepolymer based on polyethylene glycol (PEG), a highly hydrophilic oligomer, and hexamethylene diisocyanate (HDI). The bulk and surface characteristics of these materials were analyzed by differential scanning calorimetry (DSC), tensile testing, scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), electron spectroscopy for chemical analysis (ESCA), and contact angle measurement. The PU/PS IPNs prepared in this study exhibited phase separated structures, which had dispersed PS domains in the continuous PU matrix, in both the bulk and surface showing two transition temperatures. The IPN containing 50 wt% of PS showed good mechanical properties. The enrichment of PU phase in the surface was revealed by SEM, ATR-FTIR, ESCA, and contact angle measurement.

Biocompatible Materials↗

Antithrombogenicity of hydrophilic polyurethane-hydrophobic polystyrene IPNs. II. In vitro and ex vivo studies.

To investigate the effect of hydrophilic and hydrophobic surfaces with phase separated structure on their blood responses, interpenetrating polymer networks (IPNs) composed of hydrophilic polyurethane (PU) and hydrophobic polystyrene (PS) were prepared by simultaneous polymerization. In vitro protein adsorption, in vitro platelet adhesion, and ex vivo A-A shunt test were carried out to evaluate the blood compatibility of the PU/PS IPNs. The results of protein adsorption on the PU/PS IPN surfaces indicated that albumin preferentially adsorbed on the hydrophilic surface (PU), while fibrinogen preferentially adsorbed on the hydrophobic surface (PS). The PU/PS IPNs exhibited suppressive properties for both platelet adhesion and activation. The occlusion time of U50S50 IPN containing 50 wt% of PS was twice as long as that of the PU control (50 min), indicating enhanced blood compatibility, presumably due to the selective adsorption of plasma proteins and the suppression of the adhesion and activation of platelets.

Adsorption↗

In vivo evaluation of polyurethanes based on novel macrodiols and MDI.

A series of novel polyurethane elastomers based on methylenediphenyl diisocyanate, 1,4-butanediol and the macrodiols, poly(hexamethylene oxide), poly(octamethylene oxide), and poly(decamethylene oxide) were implanted subcutaneously in sheep for periods of 3 and 6 months. The specimens that were subjected to 3 months of implantation were strained to 250% of their resting length, while those implanted for 6 months had no applied external strain. SEM examination of the explanted specimens revealed that the novel materials displayed resistance to environmental stress cracking. Proprietary materials, Pellethane 2363-80A, Biomer and Tecoflex EG-80A, which had been implanted under identical conditions, showed evidence of significant stress cracking. The extent of stress cracking in the 3-month strained experiment was similar to that from the 6-month unstrained experiment. Stress cracking was also observed in Pellethane 2363-55D, when implanted for 6 months (unstrained). Neither changes in molecular weight nor in tensile properties provided a clear indication of early susceptibility to degradation by environmental stress cracking.

Animals↗

Rapid postadsorptive changes in fibrinogen adsorbed from plasma to segmented polyurethanes.

Fibrinogen adsorbed to biomaterials plays a key role in mediating platelet interactions that can lead to blood clotting so its behavior on surfaces is of fundamental interest. In previous work showing that fibrinogen adsorbed to surfaces quickly becomes non-displaceable upon exposure to blood plasma, the fibrinogen was adsorbed from buffer, so we performed new studies in which the displaceability of fibrinogen adsorbed from plasma was characterized. Fibrinogen was adsorbed from 1% plasma to seven different surfaces for 1-64 min and then transferred to 100% plasma lacking radiolabeled fibrinogen and the amount adsorbed before and after transfer measured. The surfaces were glass, Silicone rubber, and five different polyurethanes. As adsorption time increased, the fibrinogen became increasingly resistant to displacement during the 100% plasma step, but the rate of increase in resistance varied greatly with surface type. Fibrinogen adsorbed from 1% plasma evidently undergoes rapid, surface dependent transitions. This work shows that the transitions that occur when the fibrinogen is adsorbed from blood plasma are similar to what we have previously observed for fibrinogen adsorbed from buffer.

Adsorption↗

Sulfonated poly(ethylene oxide)-grafted polyurethane copolymer for biomedical applications.

Sulfonated poly(ethylene oxide) (PEO-SO3)-grafted polyurethane (PU) copolymer (PU-PEO-SO3) was developed for utilization as a material for biomedical applications. Its bulk properties and biocompatibility were investigated and the results were compared to those of PU and PU-PEO (not sulfonated). PU-PEO-SO3 copolymer showed higher water uptake than PU and PU-PEO, indicative of increased hydrophilicity due to the grafting of PEO-SO3. Compared with PU, PU-PEO-SO3 displayed lower glass transition temperature (Tg) and melting endotherm from DSC analysis, suggesting the increase of microphase separation and the suppression of hard-segment packing. PU-PEO-SO3 had practically similar mechanical properties to PU, indicating that the chemical modification of PU was accomplished without reducing its bulk properties. From the results of biocompatibility tests, PU-PEO-SO3 copolymer showed significantly lower adhesion of platelets and S. epidermidis than PU control and PU-PEO. In addition, the platelet factor 4 (PF4) released from platelets was the lowest in PU-PEO-SO3 among the test materials. PU-PEO-SO3 copolymer, which has excellent mechanical properties and biocompatibility, is expected to be useful as coating, molding, and blending materials for artificial organs and medical devices.

Alkanesulfonates↗

Phosphorylcholine-containing polyurethanes for the control of protein adsorption and cell attachment via photoimmobilized laminin oligopeptides.

In this study, we synthesized a biomaterial whose surface inhibits non-specific protein and cell attachment. The polymer was designed to mimic the external cell plasma membrane properties through the introduction of particular chemical constituents of the cell membrane: phospholipid polar headgroups. This was done by copolymerizing phosphorylcholine (PC) groups into a polyurethane polymer backbone (PCPUR). Peptides known to induce specific cell attachment were subsequently bound to the surface of this copolymer in a photoadressible manner to obtain surfaces that allowed the attachment of cells in a specific pattern. Two polymers with different phosphorylcholine concentrations were synthesized and their bulk and surface properties were characterized through differential scanning calorimetry, wettability measurements, angle-resolved X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. Protein and lipid adsorption investigation using optical waveguide light mode spectroscopy showed that the irreversible adsorption of both proteins and lipids is drastically reduced as a result of simultaneous contributions of the PC groups, molecular mobility and strong hydrophilicity of the polymers. Consequently, this leads to a marked reduction in the cellular attachment response, which further decreases with increasing PC concentration. Finally, when the polymer surface was photo-derivatized, attachment of the neural NG108-15 cell line occurred only on the areas of the PCPUR where the laminin CDPGYIGSR peptide sequence was photoimmobilized. Cell attachment was nevertheless found to be non-specific with respect to the peptide sequence used and reasons for such results are therefore discussed.

Adsorption↗

Flexible bronchoscopic removal of radioccult polyurethane foam, with pneumonitis in a hyperventilated lobe.

An intellectually delayed adult ingested and aspirated a large quantity of polyurethane foam, developing acute respiratory failure in association with partial airway obstruction. The foam was identified by flexible bronchoscopy and successfully removed from the bronchus intermedius and left mainstem bronchus with a retrieval basket. This facilitated normalization of blood gases and eventual recovery. However, the unobstructed right upper lobe became infiltrated radiographically, presumably resulting from regional hyperinflation and/or occult focal aspiration.

Adult↗

Abnormal lung function in polyurethane foam producers. Weak relationship to toluene diisocyanate exposures.

Exposures to toluene diisocyanate (TDI) were studied for effects on respiratory health of workers in two plants manufacturing polyurethane foams. Intensive personal monitoring was used to characterize job exposures. Of 4,845 12-min personal samples, 9% exceeded 5 ppb and 1% exceeded 20 ppb. Initial questionnaire and spirometry were obtained in 386 workers (88.7% of target population). Current smoking was associated with lower mean FEV1 and FEF25-75, but percent predicted (% pred) means were normal in all smoking categories. Multiple regression showed significant adverse effects of cumulative TDI exposure on initial level of FVC and FEV1 of current smokers, and an effect at borderline significance (p less than 0.063) on FEF25-75 over all smoking categories. Logistic regression showed that chronic bronchitis was more prevalent among those with higher cumulative exposures, after controlling for smoking, age, and sex. Methacholine (MCh) reactivity was associated with reduced airway function, -8.5% pred for FEV1 and -20.0% pred for FEF25-75. In 227 with adequate follow-up, the slopes of annual change were abnormal, for example, FEV1 of -67 ml/yr in current and -53 ml/yr in never smokers. Men had worse FEV1 declines than did women, -71 ml/yr versus -43 ml/yr. TDI exposure, lifetime or concurrent, had no significant effect on slopes, despite its demonstrated effects on initial level of lung function and on prevalence of chronic bronchitis.

Adult↗

Polyurethane elastomers as maxillofacial prosthetic materials.

A series of polyurethane elastomers based on an aliphatic diisocyanate and a polyether macroglycol was polymerized with various cross-link densities and OH/NCO ratios. Stoichiometries yielding between 8,600 and 12,900 gm/mole/crosslink and an OH/NCO ratio of 1.1 resulted in polymers with the low modulus, yet high strength and elongation necessary for maxillofacial applications.

Butylene Glycols↗

Care of the central venous catheterization site: the use of a transparent polyurethane film.

Studies of care of patients with central venous catheters report a 3-7% incidence of catheter-induced sepsis when sterile gauze and tape are used as an occlusive dressing. The technique requires that the dressing be changed three times each week for catheterization site inspection. From June 1979 to September 1980, a noncomparative evaluation of a transparent, self-adhesive, polyurethane dressing which is permeable to water vapor but not bacteria was performed. This dressing was used for the care of 100 consecutive patients with central venous catheters. Dressing life averaged 5.3 days with silicone rubber catheters and 4.3 days for polyvinyl chloride catheters. One patient developed catheter induced sepsis (incidence 1%). This dressing material: (1) is acceptable for use as a dressing of central venous catheters; (2) continuously permits inspection of the insertion sites; (3) decreases nursing hours; (4) provides a comfortable dressing which secures the catheter to the patient; and (5) is durable even when exposed to high humidity therapy devices, or when possible permits the patient to take showers.

Bacterial Infections↗

Material thrombogenicity in central venous catheterization: a comparison between soft, antebrachial catheters of silicone elastomer and polyurethane.

In order to compare two types of long, soft central venous catheters with the same stiffness, 39 silicone elastomer (SE) and 36 polyurethane (PU) catheters were inserted in 75 patients via basilic or cephalic veins punctured at the cubital fossa. Mean duration of catheterization was 10.5 days. Scanning electron microscopy revealed that the SE catheters to have a more uniform, but somewhat rougher surface topography than the PU catheters. The platelet adhesion in vitro to the SE catheters was four times higher than to the PU catheters. The incidence of clinical thrombophlebitis in the arm veins was 36% with the SE catheters, and 5.5% with the PU catheters (p less than 0.01). No significant differences were found between the SE and PU catheters regarding the number and size of radiologic thrombi in the peripheral and central veins, catheter occlusion rate, and platelet adhesion to the inner side of the catheter tip at withdrawal. Platelet adhesion in vivo correlated with the duration of catheterization in both groups of catheters. Mechanical trauma to the vein endothelium seems to be of vital importance in thrombus formation, but not in the induction of clinical thrombophlebitis.

Adolescent↗

Spontaneous transpyloric passage and performance of 'fine bore' polyurethane feeding tubes: a controlled clinical trial.

Certain groups of patients requiring enteral nutritional support are at increased risk of regurgitation and pulmonary aspiration of feed. Positioning of enteral feeding tubes distal to the pylorus has been advocated as a method of reducing such complications. Various techniques have been suggested to achieve postpyloric siting. Reports have indicated that lengthening the tube or altering the distal end tip configuration, by varying the tip profile or by the addition of a weight, may facilitate spontaneous transpyloric passage of the tube. This prospective controlled clinical study using three new polyurethane tubes demonstrates that the frequency of spontaneous transpyloric passage of the tube is not affected by tip profile or by the addition of a weight. Indeed, with all three tube designs only about one-third had passed spontaneously through the pylorus at 24 hr. Once through the pylorus the unweighted tube stayed in position significantly longer than the weighted tubes (p less than 0.005). We suggest that in those patients requiring post-pyloric feeding, endoscopic or fluoroscopic techniques should be used to position the tubes at the time of insertion, and that an unweighted tube should be used to prolong tube usage.

Clinical Trials as Topic↗

Subjective distress during continuous enteral alimentation: superiority of silicone rubber to polyurethane.

A small-bore feeding tube of silicone rubber was developed in order to improve the acceptance of enteral feeding. The insertion procedure was facilitated by providing a double guidewire which allows continuous adjustment of tip rigidity. The usefulness of this tube was tested in a short-term and a long-term volunteer study as well as in a prospective follow-up of patients receiving enteral nutrition. The volunteer study showed that the newly developed tube significantly reduced subjective distress (rank value 14) when compared to a conventional tube made of polyurethane (rank value 20). In the patient study, 131 silicone rubber tubes were used in 85 patients who received enteral nutrition for a total period of 2080 days and complained about foreign-body feeling and rhinorrhea in only 3.7% and 0.5% of the days, respectively. The rate of inadvertent removals was relatively low (32%), mainly due to restricted mental status of the patients.

Enteral Nutrition↗

A cuffed polyurethane catheter for long-term central venous access: a novel technique prevents early displacement.

A new method which provides immediate fixation of a cuffed central venous catheter is described. The cuffed polyurethane catheter has a detachable hub which allows the creation of a second small tunnel distal to the cuff using the wire and the vein dilator. As the catheter exits from a "pinhole," immediate fixation is assured and is independent of tissue healing.

Catheterization, Central Venous↗

Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment.

We describe a preclinical study of our original hybrid artificial liver support system (HALSS) for a clinical trial. We designed a HALSS comprising a multi-capillary polyurethane foam packed-bed module (MC-PUF module) containing a total 200 g (2 x 10(10) cells) porcine hepatocytes, and an extracorporeal circulation device. Almost all porcine hepatocytes in the MC-PUF module formed many spherical multicellular aggregates (spheroids). This extracorporeal circulation device was improved to promote solute exchange between a living body and a MC-PUF module by including a plasma bypass line in the circulation loop. The efficacy of the HALSS was evaluated using a 25-kg pig with warm ischemic liver failure by portocaval shunt and ligation of hepatic artery (HALSS group, n=3). As a control experiment, the same system without hepatocytes in the module was used with the same kind of liver failure pig (Control group, n=3). The blood ammonia in the control group was 143 N-microg/dl at the start of circulation, and rapidly increased to 351 N-microg/dl at 2 hours and to 704 N-microg/dl at 6 hours. But the blood ammonia in the HALSS group was completely suppressed, and remained less than the hepatic coma level (over 200 N-microg/dl) during the circulation time. The blood glucose in the control group gradually decreased, and became less than 40 mg/dl within 6 hours of circulation. But the blood glucose in the HALSS group was maintained well, and remained the normal glucose level (50 - 105 mg/dl) for more than 20 hours of circulation. Improvement in blood creatinine and lactate, and the stabilization of vital signs and urinary excretion, were observed in the HALSS group. The survival time of the pigs in the HALSS group was 19.3 hours compared with 8.9 hours in the control group. In conclusion, our HALSS was effective to stabilize the general conditions of the body in addition to supporting various liver functions. These results suggest that our HALSS has a strong possibility to be used in treating liver failure patients. We have applied for approval of the clinical trial of our HALSS to our institutional ethics committee.

Animals↗

Recovery of rats with fulminant hepatic failure by using a hybrid artificial liver support system with polyurethane foam/rat hepatocyte spheroids.

We studied the recovery of rats with fulminant hepatic failure (FHF) by treating them with our original hybrid artificial liver support system (HALSS). FHF was induced by a two-thirds partial hepatectomy and 10 minutes of hepatic ischemia. Rats with FHF were treated with a polyurethane foam/spheroid HALSS including 2.0 x 10(8) hepatocytes for 1 hour (HALSS group, n = 5), and with the same system without hepatocytes in the artificial liver module as a control experiment (sham-HALSS group, n = 3). The level of blood constituents, ammonia, glucose and creatinine, showed no major difference between the two groups at the end of treatment. All rats in the sham-HALSS group died within 5 hours after treatment. However, the level of blood constituents of rats with FHF in the HALSS group improved with time, and all rats in the HALSS group recovered. Liver tissue of rats treated with HALSS showed cell mitosis and improvement from injury. These results indicated that our HALSS has a strong possibility to induce recovery from hepatic failure.

Ammonia↗