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PubMedDate not supplied

Development of novel submicron textured polyether(urethane urea) for decreasing platelet adhesion.

Ventricular assist devices have proven to be a useful clinical option for providing circulatory support as a bridge to transplantation and a mode of destination therapy. Thromboembolism is prevented by designing devices that use blood interfaces that either encourage biological material deposition and strong adhesion, or discourage deposition via surface chemistry, surface finish, and fluid flow fields. Minimum continuous or periodic wall shear forces and maximum time at reduced shear are important, and sometimes difficult-to-satisfy, design constraints. We present an approach to reducing platelet adhesion via surface topography, reducing surface area for platelet-material interaction. Large areas of polyether(urethane urea) were textured with two different sizes of ordered pillar arrays via two-stage replication molding without affecting surface chemistry. Pillars had subplatelet dimensions designed to reduce the surface area a platelet may contact. Platelet adhesion was assessed in a physiologically relevant shear stress range from 0-10 dyn/cm2 using a rotating disk and compared to smooth control. Adhesion was highest from 0-5 dyn/cm2. Surface texturing reduced platelet adhesion without increasing platelet activation in bulk suspension. This study demonstrates that material surface texture is an additional variable that may be used to reduce platelet adhesion under low shear stresses potentially reducing thromboembolism.

Biocompatible Materials↗
PubMed1995

Hydrolytic stability of silanated zirconia-silica-urethane dimethacrylate composites.

The effect of the method of silanation of zirconia-silica by 3-methacryloxypropyltrimethoxysilane (MAPM) and 3-acryloxypropyltrimethoxysilane (APM) on the diametral tensile and transverse strength of composites made from these silanated fillers and a urethane dimethacrylate was determined after 0-108 h of boiling in water. The water sorption of these composites was also measured at times up to 108 h. Silanation with either silane significantly increased the tensile and transverse strengths and decreased water sorption relative to comparable unsilanated controls. Silanation with MAPM from ethanol solution at three times the minimum uniform coverage gave the best overall results, and the tensile strength tests appeared to be most predictive of effectiveness of the silane treatments.

Absorption↗
PubMed2006

Intrathecal glutamate promotes glycinergic neuronal activity and inhibits the micturition reflex in urethane-anesthetized rats.

OBJECTIVES: In order to clarify the role of glutamate in the micturition reflex and in glutamatergic and glycinergic neuronal activity, we examined the effects of intrathecal (IT) injection of glutamate or MK-801 (an N-methyl-D-aspartate receptor antagonist) on bladder activity and on the glutamate and glycine levels in the lumbosacral cord of female rats with or without acute lower thoracic spinal cord injury (SCI). METHODS: Under urethane anesthesia, isovolumetric cystometry was performed in rats with or without SCI before and after IT injection of glutamate or MK-801 at the lumbosacral cord level. The glutamate and glycine levels of the whole lumbosacral cord were measured after IT injection of glutamate or MK-801 in both groups. RESULTS: In intact rats, IT glutamate (100 microg) prolonged the interval between bladder contractions and decreased the amplitude of contractions. IT MK-801 (3-100 microg) also prolonged the interval between bladder contractions and decreased the amplitude in intact rats. In SCI rats, cystometry demonstrated the disappearance of bladder contractions, and the glycine level in the lumbosacral cord was elevated. In intact rats, IT glutamate (0.3-100 microg) increased the glycine level in the lumbosacral cord. On the other hand, IT MK-801 (3-100 microg) decreased both glutamate and glycine levels in intact and SCI rats. CONCLUSIONS: These results suggest that glutamatergic neurons have stimulatory projections to both glutamatergic and glycinergic neurons in the lumbosacral cord, and that glutamatergic neurons inhibit the micturition reflex by stimulating glycinergic neurons.

Animals↗
PubMed1989

Clinical application of a self-sealing poly(ether-urethane) graft applicable to blood access for hemodialysis.

A poly(ether-urethane) graft (PEU) has been developed by our group and examined clinically. From July 1986, four straight and 11 loop grafts were implanted in 15 patients on maintenance hemodialysis. One straight and three loop grafts thrombosed between 1-6 months after the operation. One loop graft was ligated to remedy edema caused by a preexisting subclavian vein thrombosis. Angiographic findings of the grafts revealed a smooth positioning of the graft in most of the cases with minimal to moderate stenosis at anastomotic sites. Punctured sites were identified as tiny filling defects on the wall. However, neither stenosis nor aneurysmal dilatation were observed. Specimens of the graft were obtained from three patients to examine histological findings. Neointimal coverage was observed near the anastomotic site in a specimen obtained 6 months after the operation. The bare luminal surface still remained at the center of the graft. No clinical sign of peripheral thrombi was found. In addition to the clinical experience, this study is supplemented with the preliminary result of an animal experiment using a newly modified PEU graft with an open structure on the luminal surface.

Animals↗
PubMed2005

Structure and relaxation dynamics of poly(amide urethane)s with bioactive transition metal acetyl acetonates in hard blocks.

Structural characteristics, thermal transitions and molecular dynamics of selected poly(amide urethane)s with transition metal acetyl acetonates Me(AcAc)(2) (Me = Sn(4+), Zn(2+), Cu(2+), Pb(2+)) as chain extenders, were comparatively investigated using small- and wide-angle X-ray scattering (SAXS, WAXS), differential scanning calorimetry (DSC), and dielectric techniques (dielectric relaxation spectroscopy, DRS; thermally stimulated currents, TSC). We studied the influence of metal chelates on the mixing of the soft-segment (SS) and hard-segment (HS) domains and the related degree of microphase separation (DMS). The reactivity of Me(AcAc)(2) with macrodiisocyanate was found to decrease in the order Sn(AcAc)(2)Cl(2) > Cu(AcAc)(2) > Zn(AcAc)(2) > Pb(AcAc)(2). While Pb(AcAc)(2) shows a higher tendency for crystallisation, both the dielectric and calorimetric results suggest that the corresponding polyurethane has comparatively low DMS. The type of the transition metal has moderate effect on the glass transition temperature and no influence on the shape of the dielectric alpha relaxation signal, indicating weak interactions between metal ions and SS domains. In contrast, structural parameters and the dielectric behaviour of the beta relaxation suggest preference for hydrogen-bonding interactions between Sn(4+) and Cu(2+) metal-chelates and HS domains. The temperature dependence of dc conductivity sigma(dc) is described by the Vogel-Tammann-Fulcher equation and signifies the coupling between the mobility of polymeric chains and charges' motion. It may be expected that the present combination of techniques and particular results with respect to DMS will contribute to the development and testing of novel biodegradation-resistant and antibacterial metal-polyurethanes for biotechnological and industrial applications.

Amides↗
PubMed1983

Ectopic growth hormone-releasing factor stimulates growth hormone secretion in the urethane-anesthetized rat in vivo.

The in vivo bioactivity of ectopic growth hormone-releasing factor (GHRF) was examined in estrogen-primed, urethane-anesthetized male rats bearing intracarotid catheters. Ectopic GHRF was isolated from a carcinoid tumor metastatic to the liver from a patient with gigantism and elevated plasma growth hormone (GH) levels and was partially purified by reverse phase high performance liquid chromatography for intracarotid injection. Ectopic GHRF elicited a promt rise in plasma GH which peaked at 5 min. The time course of the response resembled that to prostaglandin E1, a known potent direct stimulator of GH secretion in vivo. The effect of ectopic GHRF was dose related in the range of 10-100 U/rat which represents approximately 30x the effective in vitro dose range/10(5) cells in rat adenohypophyseal cell cultures. The in vivo response to ectopic GHRF was completely blocked by the simultaneous intracarotid administration of the GH release inhibitory peptide, somatostatin. These findings lend further support for a role of GHRF from human tumors as a potent physiological stimulator of GH release.

Animals↗
PubMed2001

Selective binding of albumin on stearyl poly(ethylene oxide) coupling polymer-modified poly(ether urethane) surfaces.

A tri-block-coupling polymer of stearyl poly(ethylene oxide)-4,4'-methylene diphenyl diisocyanate-stearyl poly(ethylene oxide) (MSPEO), was used as a surface modifying additive (SMA) and the MSPEO-modified poly(ether urethane) (PEU) surfaces were prepared by the process of dip-coating. The surface analysis by XPS revealed the surface enrichment of poly(ethylene oxide) (PEO). On the coating-modified surfaces, the bovine serum albumin (BSA) adsorption, respectively, from the low and high BSA bulk concentration solutions was correspondingly characterized by the methods of radioactive 125I-probe and ATR-FTIR. The bovine serum fibrinogen (Fg)-adsorption from the Fg bulk solution and the BSA-Fg competing adsorption from the BSA-Fg binary solutions were also characterized by radioactive 125I-probe. The reversible BSA-selective in situ adsorption on MSPEO-modified PEU surfaces were achieved, and the performance of blood compatibility on the coating-modified surfaces was also confirmed, respectively, by plasma recalcification time (PRT) and prothrombin time (PT) tests.

Adsorption↗
PubMed2002

Influence of surface morphology and chemistry on the enzyme catalyzed biodegradation of polycarbonate-urethanes.

Polycarbonate based polyurethanes were synthesized with varying hard segment content as well as hard segment chemistry based on three different diisocyanates,1,6-hexane diisocyanate (HDI), 4.4'-methylene bisphenyl diisocyanate (MDI) and 4,4-methylene biscyclohexyl diisocyanate (HMDI). The surface chemistry and morphology were characterized using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The polymers were incubated with cholesterol esterase (CE) in a phosphate buffer solution at 37 degrees C over 10 weeks. XPS results showed that the surface chemistry changed as the size and chemistry of the hard segment varied within the materials. AFM images exhibited distinctive surface morphologies for all polymers, and this was particularly apparent with changes in the hard segment chemistry. The results showed that the surface of HDI polymers consisted of relatively stiff rod-like structures, which corresponded to the soft segment domains. Polymers with a higher HDI content exhibited a dense top layer containing a relatively higher hard segment component, covering the sub-surface matrix of rod like structures. The MDI based polyurethane had large aggregates on its top surface, which corresponded to the aggregation of harder components. The HMDI based polycarbonate-urethane presented a relatively homogeneous surface where no phase separation could be detected. The relative differences in hard and soft segment content in their surface structure was supported by XPS findings. The analysis of the biodegradation results, concluded that enzyme catalyzed biodegradation within these materials was initiated in amorphous soft segment regions located in the region of the interface between hard and soft segments. A higher hard segment content at the surface contributed significantly to an increase in biostability. The findings provided an enhanced understanding for the role of surface molecular structure in the enzyme catalyzed biodegradation of polyurethanes.

Biocompatible Materials↗
PubMed2002

Grafting sulfobetaine monomer onto the segmented poly(ether-urethane) surface to improve hemocompatibility.

Polyurethanes are widely used as blood-contacting biomaterials, due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more demanding applications. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of the present study was to synthesize a novel nonthrombogenic biomaterial by modifying the surface of polyurethane. Ozonization was used to introduce active peroxide groups onto the segmented poly(ether-urethane) (SPEU) film surface and graft polymerization of N,N'-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate (DMAPS), a sulfobetaine structure, onto the ozone-activated SPEU surface was conducted. The SPEU-g-PDMAPS film was characterized by ATR-FTIR, XPS, and contact angle measurements. ATR-FTIR and XPS confirmed the graft polymerization. The grafted film possessed a relatively hydrophilic surface, as revealed by contact angle measurement. The blood compatibility of the grafted films was evaluated by a platelet-rich plasma (PRP) adhesion study and scanning electron microscopy, using SPEU film as the reference. No platelet adhesion was observed for the grafted films incubated with PRP at 37 degrees C for 60 and 180 min. This new sulfobetaine structure grafted biomaterial might have potential for biomedical applications.

Betaine↗
PubMed2003

Synthetic studies on nonthrombogenic biomaterials 14: synthesis and characterization of poly(ether-urethane) bearing a Zwitterionic structure of phosphorylcholine on the surface.

A new Zwitterionic compound of the phosphorylcholine analogue, 4-hydroxylbutyl phosphorylcholine (HBPC), was synthesized and characterized. HBPC was chemically tethered onto the surface of poly(ether-urethane) (PEU) films with hexamethylene diisocyanate (HDI) as a coupling agent. The existence of a phosphorylcholine structure on the PEU surface was demomstrated by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FT-IR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. The nonthrombogenicity of the modified films was evaluated by platelet-rich plasma (PRP) assay. The results showed that films grafted with HBPC have excellent platelet adhesion resistance.

Biocompatible Materials↗
PubMed2005

Poly(ether urethane)s incorporating long alkyl side-chains with terminal carboxyl groups as fatty acid mimics: synthesis, structural characterization and protein adsorption.

The object of this work was to produce polyurethanes with greater affinity for albumin (Alb) and improved hemocompatibility by introduction of carboxyl-terminated alkyl side-chains that better mimic fatty acids, in contrast to methyl terminated alkyl side-chains used previously. Synthesis of poly(ether urethane)s (PEUs) with long alkyl side-chains via a multi-step solution addition polymerization is described. The synthesis is based upon the polymerization of a diisocyanate pre-polymer with various chain extenders and reaction with Br-terminated compound in the final stage. The side-chains had terminal methyl or carboxylic groups, and were attached either directly to the polymer backbone or to an oligo(ethylene glycol) spacer. The bulk structure of the PEUs was confirmed by 1H-NMR and the surface polymer structure was characterized by ToF-SIMS. The influence of the incorporated C16-alkyl, C16-carboxyalkyl and oxyethylene-C16-carboxyalkyl side-chains attached to the polymer backbone on fibrinogen (Fg) and Alb adsorption from blood plasma, and Fg adsorption from buffer solutions and binary mixtures with Alb was measured. Incorporation of C16-alkyl or C16-carboxyalkyl side-chains into PEUs caused relatively small changes in Fg and Alb adsorption. PEUs with oxyethylene-C16-carboxyalkyl side-chains exhibited the lowest Fg adsorption and the highest Alb adsorption among all the tested polymers.

Adsorption↗
PubMed2006

Atomic force microscopy visualization of poly(urethane urea) microphase rearrangements under aqueous environment.

Polyurethane biomaterials are a critically important class of polymers used in a variety of medical devices. It has been suggested that the good blood compatibility of polyurethanes arises from nanoscale chemical heterogeneities at the surface as a consequence of the microphase separated morphology. In this study, we used tapping mode atomic force microscopy with phase imaging under aqueous conditions to visualize the distribution of the surface microphases for a series of poly(urethane urea) block co-polymers with varying hard segment content. The surfaces were prehydrated for 24 h under a flow of 1 mM phosphate buffer. Topographic images showed the formation of nanometer-sized raised features on the surface, having lateral dimensions of 50-70 nm and heights of 10-15 nm. Phase images, reflecting the local distribution of the mechanical properties under aqueous conditions, were quite different from those obtained in ambient conditions, consistent with water-induced structural reorientation. Images suggest that there is little soft phase material at the polymer surface in the presence of water, while images acquired after dehydration of the samples show that the surface layer remains rich in hard domains, indicating that the films do not return to their original states over the time period studied.

Microscopy, Atomic Force↗
PubMed2006

Select bladder smooth muscle cell functions were enhanced on three-dimensional, nano-structured poly(ether urethane) scaffolds.

Bladder wall resection is often required as a treatment for invasive bladder cancer. When this happens, a suitable replacement material is needed. The present study, therefore, created three-dimensional, porous, nano-structured poly(ether urethane) (PU) matrices for use as bladder tissue-engineering scaffolds. Select cytocompatibility experiments (specifically adhesion and long-term growth studies) were performed on these scaffolds using human bladder smooth muscle cells (BdSMCs). In addition, the amount of total collagen and elastin present in each cell-seeded scaffold was determined since the production of these extracellular matrix (ECM) proteins is essential for the health and survival of cells and for the functionality of the replaced organ. Finally, to better understand how these scaffolds and resident cells would perform in the complex mechanical environment of the bladder wall, scaffolds and cells were subjected to 10 cmH2O pressure using a computer-controlled pressure chamber. Results provided evidence that compared to conventionally used, micro-dimensional PU scaffolds, the novel, nanodimensional scaffolds created in this research increased cell adhesion, growth, and ECM protein production. Additionally, scaffolds and resident cells were not affected by exposure to 10 cmH2O pressure (compared to controls maintained under atmospheric conditions). These results are promising and provide evidence that the nano-dimensional PU scaffolds created in this research are suitable bladder replacement materials that may outperform materials currently used for such purposes.

Animals↗
PubMed1993

Synthesis and characterization of putrescine-based poly(phosphoester-urethanes).

A novel set of putrescine-based segmented polyurethanes was synthesized using 1,4-butane-diisocyanate and phosphoester diols, and was characterized for its potential as a degradable biomaterial. These poly(phosphoester-urethanes) (PPU) were flexible polymers with ultimate tensile strength (UTS) from 2 to 3 MPa, elongations up to 80% and tan delta near 0.15. The incorporation of phosphoester bonds in the backbone of the polymer by using bis(2-hydroxyethyl)phosphite (BGP) and bis(6-hydroxyhexyl)phosphite (BHP) as chain extenders resulted in hydrolytic degradation which was evaluated in vitro. By varying the content of the phosphoester diol BGP, degradation rate, as followed by mass loss and GPC, could be modulated. Polymers based on the more hydrophobic monomer, BHP, showed slower degradation than corresponding BGP based polymers. Tensile properties of PPU-B2 after 22 days in vitro degradation show more than a 50% drop in UTS and ultimate elongation, likely caused by void spaces left behind in the polymer after mass loss and swelling. The attachment of a drug, PAS, pendant to the phosphoester group of the PPU was demonstrated. PAS was linked via the spacer 4-hydroxybenzaldehyde, and free, intact drug was released in about 5 h from a thin film.

Aminosalicylic Acid↗
PubMed1996

Modification of poly(ether urethane)elastomers by incorporation of poly(isobutylene)glycol. Relation between polymer properties and thrombogenicity.

Non-polar hydrophobic poly(isobutylene)glycol (PIBG) was substituted for poly(tetramethylene ether)glycol (PTMEG) in poly(ether urethanes) based on 4,4'-methylenebis-(phenylisocyanate) (MDI) and 1,4-butanediol (BD) as chain extender. Two series of polyurethanes differing in their soft segment length, polymer composition, and hard segment content were studied by dynamic mechanical analysis (DMA) and static, as well as dynamic, contact angle measurements. The thrombogenicity of these polymers was characterized by studying the adhesion and activation of platelets using ELISA for GMP 140 and fluorescence microscopy. It was found by DMA that in PIBG-containing polyurethanes (PUE) exist soft domains containing hard segments, strictly separated hard segment domains, and hard segments partially mixed with soft segments. Contact angle measurements revealed that 25% PIBG or even less, are sufficient for a remarkable enrichment of these non-polar soft segments on the polymer surface. The platelet adhesion/activation on these materials was demonstrated to increase with the rise in hard segment content, as well as with an enhancement of the PIBG content. However, comparison of PIBG-containing PUE with medical applied polypropylene and pellethane expressed that PUE with PIBG content equal or less 25% have excellent haemocompatibility.

Biocompatible Materials↗
PubMed1990

Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine.

The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.

Analysis of Variance↗
PubMed1985

Growth hormone response to thyrotropin-releasing hormone in the urethane-anesthetized rat: effect of thyroid status.

To evaluate the role of thyroid hormones in regulation of the GH-stimulatory effects of TRH and human pancreatic GH-releasing factor (hpGRF-40), we studied the plasma GH responses to these secretagogues under conditions of thyroid hormone deprivation and replacement in the urethane-anesthetized rat. In euthyroid control rats, TRH (1 microgram/kg) elicited a small transient rise in plasma GH, which peaked at 2-5 min and returned to basal by 20 min. In chronically hypothyroid rats (10 weeks after thyroidectomy), intrapituitary GH was markedly depleted to less than 0.1% of normal, and TRH was completely ineffective in eliciting a plasma GH response to TRH. In chronically hypothyroid rats given T4 (20 micrograms/kg daily) for 4 days, intrapituitary GH was partially repleted, and the GH response to TRH was markedly enhanced compared to that in euthyroid rats. The extent to which the GH response to TRH was enhanced by chronic hypothyroidism, followed by short term T4 treatment, depended on the duration of T4 administration. The plasma GH response was greatest after 1-3 days of T4 treatment; treatment for 7 days, on the other hand, suppressed the GH response to below that of euthyroid rats. The minimal duration of hypothyroidism which, in combination with short term (2 days) T4 treatment, enhanced the plasma GH response to TRH, was 6 weeks, with 8 weeks or longer being optimal. The effect of TRH on plasma GH was dose dependent in thyroidectomized rats given T4 for 2 days; the lowest maximally stimulatory dose was 10 times less than that in the euthyroid rat (1 vs. 10 micrograms/kg). The GH-stimulatory effect of TRH in thyroidectomized rats given T4 for 2 days was abolished by the simultaneous administration of SRIF (40 micrograms/kg). That the failure of TRH to stimulate GH release in the chronically hypothyroid rat may have been the consequence of a depletion of intrapituitary GH available for release was suggested by the finding that in parallel studies, hpGRF-40, a more potent stimulator of GH release in the euthyroid rat, was also without effect. In contrast to the GH response to TRH, the GH response to hpGRF-40 was only partially restored by T4 treatment of chronically hypothyroid rats for 2 days. We conclude that chronic thyroid hormone deficiency selectively sensitizes the somatotroph to TRH. Short term thyroid hormone replacement is needed to replete intrapituitary GH and allow the expression of this enhanced GH secretory response to TRH. More prolonged treatment with T4, on the other hand, appears to desensitize the somatotroph to TRH.

Animals↗
PubMed1988

Effect of pentobarbital on gastric acid secretion elicited by secretagogues or electrical vagal stimulation in rats under urethane anesthesia.

The effect of pentobarbital, which stimulates gastric acid secretion in urethane-anesthetized rats, on secretagogue-stimulated or electrically stimulated acid secretion was studied in the rat perfused stomach. 2-Deoxy-D-glucose (2-DG)-stimulated gastric acid secretion was markedly depressed by intravenous injection of pentobarbital, but was definitely increased by lateral cerebroventricular injection and was unaffected by injection into the fourth cerebroventricle. Bethanechol-stimulated secretion was augmented by intravenous injection of pentobarbital. In vagotomized rats, pentobarbital did not affect the bethanechol-stimulated or electrically vagally stimulated secretion. These findings indicate that pentobarbital produces both stimulatory and inhibitory effects on gastric acid secretion through a central mechanism, especially in the forebrain. It was proposed that the inhibitory response would result from some interaction of intravenous 2-DG and pentobarbital in the central regulatory system of gastric secretion.

Animals↗