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Synthesis of phospholipid polymers having a urethane bond in the side chain as coating material on segmented polyurethane and their platelet adhesion-resistant properties.

Surface modification of segmented polyurethanes (SPUs) was carried out using new blood compatible polymers having both phospholipid polar groups and urethane bonds in the side chains. The polymers were composed of 2-methacryloyloxyethyl phosphorylcholine (MPC), n-butyl methacrylate (BMA) and methacrylate with a urethane bond (MU). The MPC copolymers were soluble in ethanol. The SPU membranes were immersed in an ethanol solution of MPC copolymers and dried in vacuo for coating. The surface formed was completely covered with the MPC copolymer which was confirmed by X-ray photoelectron spectroscopic analysis. The polymer coatings were hardly detached in water, ethanol and 40% aqueous solution of ethanol compared with poly(MPC-co-BMA) which did not have the MU moieties. Therefore, the MU moieties had affinity for the SPU. The surface modification of the SPUs suppressed platelet adhesion effectively after contact with platelet-rich plasma for 180 min.

Biocompatible Materials↗

Dental application of polyfunctional urethane comonomers to composite resin veneering materials.

Urethane monomer/diluent monomer mixtures were used in dental composite resin veneering materials filled with various ratios of powder (filler)/liquid (comonomer), P/L. Hardness values of unfilled resins containing benzoyl peroxide only (BP0; 0.5 wt%), and filled resins (included trimethylol propane trimethacrylate (TMPT) composite filler) were tested. Significant increases in hardness were obtained with the use of TMPT composite filler in the resins. Also, their modulus values measured by bend test showed an increasing trend, compared to a commercial composite resin veneering material (a control sample; CONT) with a lower filler content (50 wt%). The DME-DPMDC/HPDM comonomer (dimethacryloxyethyl diphenylmethane-4,4'-dicarbamate/hydroxypropyl dimethacrylate), which showed a smaller fraction of surface porosity, gave greater mechanical strength values at P/L ratios of 0.55 (17.8 wt% filler content) to 1.20 (27.3 wt%) than a CONT resin. The coefficient of thermal expansion was smaller in urethane-based filling materials than a CONT resin. Also, greater activation energy of thermal decomposition was observed in the resin samples with P/L ratio 0.75 to 1.20 than in a CONT resin. Thermally-induced decomposition occurred with smaller weight loss in the experimental filled resins than in a CONT resin.

Journal Article↗

Investigation of the ability of MDHS method 25 to determine urethane-bound isocyanate groups.

Method 25 for the Determination of Hazardous Substances (MDHS 25) of the Health and Safety Executive of the United Kingdom attempts to identify and quantify all isocyanate species in an air sample. Isocyanate species are derivatized with 1-(2-methoxyphenyl)piperazine (MOPP) and analyzed by high-performance liquid chromatography (HPLC) with tandem ultraviolet/electrochemical (UV/EC) detection. The method identifies peaks as being isocyanate-derived if the EC/UV detector response ratio is between 0.75 and 1.5 times that of the derivatized monomer. This investigation sought to determine if the method correctly identifies and accurately quantifies intermediates created during polyurethane formation that possess free isocyanate groups. Model compounds derived from 2,4-toluene diisocyanate (2,4-TDI) and ethylene glycol were prepared. These urethane species contained two ("dimer") and three ("trimer") TDI units and terminal MOPP-derivatized isocyanate groups. Like monomeric 2,4-TDI/MOPP urea, each contained two derivatized isocyanate groups per molecule. This investigation found that neither the UV nor the EC response is proportional to the number of isocyanate groups present in the model compounds. Therefore, it is concluded that MDHS 25 is neither capable of correctly identifying TDI-urethane intermediates possessing MOPP-derivatized isocyanate groups nor is it capable of accurately quantifying these isocyanate groups. The proposed solution to this problem is the utilization of a derivatizing reagent that yields derivatized isocyanate species whose detector responses come more exclusively from the derivatized isocyanate moiety and, therefore, are more proportional to the number of derivatized isocyanate groups.

Chromatography, High Pressure Liquid↗

Novel poly(urethane-aminoamides): an in vitro study of the interaction with heparin.

In order to obtain heparin-binding polyurethanes, tertiary amino-groups have been introduced in the polymer backbone by attributing a key-role to the chain extender, i.e. substituting butanediol, commonly used in polyurethane synthesis, with a tailor-made diamino-diamide-diol. In this work a poly(ether-urethane-aminoamide) (PEU/PIME/al) was obtained with poly(oxytetramethylene) glycol 2000, 1,6-hexamethylene-diisocyanate and the new chain extender, in the molar ratio 1:2:1. The heparin binding capacity of PEU/PIME/al was evaluated with 125I labelled heparin, using for comparison the analogous polymer obtained with a diamide-diol (i.e. the poly(ether-urethane-amide) PEU/PIBLO/al), and two commercially available biomedical polyurethanes (Pellethane 2363 and Corethane). pH and ionic strength dependence of the heparin uptake were investigated by treating all the polyurethanes with solutions of 125I heparin into buffers from pH 4 to 9 or NaCl molarity from 0.0 to 1.0. The stability of the interaction with bound heparin was investigated by sequential washing treatments (PBS, 1 N NaOH, 2% SDS solution), then analysing the residual radioactivity on the materials. Results indicated that the heparin binding of PEU/PIME/al is significantly higher and more stable than that of the other polyurethanes, with a time-dependent kinetic. The interaction with heparin appears to be prevalently ionic, with the contribution of other electrostatic and hydrophobic interactions. Activated partial thromboplastin time (APTT), performed on human plasma with polyurethane-coated, heparinized test tubes, indicated that bound heparin maintains its biological activity after the adsorption.

Animals↗

Isocyanate-terminated urethane prepolymer as bioadhesive material: evaluation of bioadhesion and biocompatibility, in vitro and in vivo assays.

Attempts have been made to evaluate the degree of bioadhesion and biocompatibility of a synthesized urethane prepolymer with specially tailored microstructure. Wetting behaviour and extent of interfacial adhesion of the prepared prepolymer towards biological substrates were examined by in vitro methods. The former was carried out by measuring the contact angle between drops of the prepolymer liquid and a biological surface, while the latter was determined from the force between the prepolymer and tissue model or mucus. The obtained results exhibited good tissue wettability and bioadhesion by the prepolymer. Preliminary evaluation of biocompatibility for the uncatalytically cured prepolymer films was performed by cytotoxicity and histotoxicity experiments. Results showed a significant growth for the adhered L929 fibroblast cells within a period of 5 days incubation. Also, no severe inflammatory tissue response towards the samples implanted in rabbit for 16 weeks was seen. These observations can support the potentiality of the designed urethane prepolymer to be applied as hemostatic agent.

Adhesiveness↗

Poly(ether) urethane reactivity with metal-ion in calcification and environmental stress cracking.

Since their introduction to the biomedical community in 1967, polyurethanes have been used in a number of biomedical applications. In chronic applications evidence is now available which suggests that polyurethanes may be subject to various cracking phenomena. Environmental stress cracking and calcification are two phenomena resulting in poly(ether)urethane cracking, which have been shown to be enhanced by ion complexation. Much evidence now exists which defines the ability of poly(ether)urethanes to selectively extract ions, especially calcium ion from solution. Metal ion binding appears to enhance environmental stress cracking and appears to be a first step in the process of calcification.

Biocompatible Materials↗

Chemical and physical characterization of a novel poly(carbonate urea) urethane surface with protein crosslinker sites.

A major complication which occurs with implantable polyurethane biomaterials is bioincompatibility between blood and the biomaterial surface. Development of a novel biodurable polyurethane surface to which biological agents, such as growth factors or anticoagulants could be covalently bound, would be beneficial. The purpose of this study was to synthesize a novel poly(carbonate urea) urethane polymer with carboxylic acid groups which would serve as "anchor" sites for protein attachment. Physical characteristics such as tensile strength, initial modulus, ultimate elongation, tear strength, water/alcohol uptake and water vapor permeation were then evaluated and compared to other biomedical-grade polyurethanes. Covalent linkage of the blood protein albumin to this novel surface was then examined. A biodurable polycarbonate-based polyurethane containing carboxylic acid groups (cPU) was synthesized using a two step procedure incorporating the chain extender 2,2-bis(hydroxymethyl)-propionic acid (DHMPA). Tensile strength of this cPU film was 2.7 and 2.6 fold greater than both a polycarbonate-based polyurethane synthesized with a 1,4-butanediol chain extender (bdPU) and Mitrathane (Mit) controls, respectively. The cPU polymer also possessed 7.8 and 31 fold greater structural rigidity upon evaluation of initial modulus as compared to the bdPU and Mit, respectively. Ultimate elongation for the bdPU films was slightly higher than the cPU and Mit films, which had comparable elongation properties. The force required to tear the bdPU film was 1.9 and 32 fold greater than the cPU and Mit films, respectively. Alcohol solution uptake by all of the polyurethane segments increased with increasing alcohol concentrations, with the cPU having the greatest uptake. Water uptake was minimal for all the polyurethanes examined and was not affected by altering pH. Water vapor permeation was lowest for the cPU films as compared to both bdPU and Mit. Swelling the cPU in 50% ethanol prior to evaluation slightly increased water vapor permeation through the films. Covalent linkage of the radiolabelled blood protein albumin (125I-BSA) to the cPU segments incubated with the heterobifunctional crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) was greatest in the higher percent of ethanol as compared to controls. These results serve as foundation for developing a novel poly(carbonate urea) urethane with physical characteristics comparable to other medical-grade polyurethanes while having protein binding capabilities.

Adsorption↗

Relationship between the suckling-induced release of oxytocin and prolactin in the urethane-anaesthetized lactating rat.

The effects of changes in the intensity of the suckling stimulus on the reflex release of oxytocin and prolactin were compared in urethane-anaesthetized lactating rats. Mothers which had previously suckled 12 pups (Group 1) showed a graded increase in the amount of oxytocin released during a 3 h suckling test when the number of pups applied to the nipples was increased from six to eight or ten. Mothers which had suckled six pups during their lactation (Group 2) appeared to show a maximum frequency of milk ejection whether six, eight or ten pups were applied to the nipples. The release of prolactin was not elicited from either Group 1 or Group 2 mothers when six pups were applied to their nipples. With eight pups suckling, the Group 1 mothers again showed no evidence of prolactin release. In contrast, the Group 2 mothers showed a significant increase in the level of prolactin in the plasma during the 3 h suckling test. With ten pups suckling the release of prolactin was evident in both groups of mothers, although the response was earlier and more pronounced in Group 2 than Group 1. These results suggest that in the urethane-anaesthetized rat, the threshold for the suckling-induced reflex release of oxytocin is distinct from the threshold for the release of prolactin and that these thresholds are, at least in part, set by the preceding suckling experience of the mothers. In those animals which showed both reflex milk ejection and prolactin release there was a linear relationship between the magnitude of the two endocrine responses.

Animals↗

[AIDS through blood contamination (early 1980s) and urethane shock (1975)].

1) AIDS contracted through contaminated blood was first discovered in the early 1980s, and related law suits are now underway. The contamination of the blood is considered to ba a shared responsibility of the "government," "medical establishments" and "industry." The revision of the Pharmaceutical Affairs Law in 1979 gave the authority for commanding the recall of products to the Health and Welfare Ministry. This was a lesson learned from past cases of drug-induced suffering. However, the ministry did nothing regarding the blood contaminated with the AIDS virus. 2) "Urethane shock (drug-induced suffering)" occurred in 1975. Although it occurred before the revision of the Pharmaceutical Affairs Law, the Health and Welfare Ministry took the administrative measure of "an immediate recall," because the antipyretic analgesic injections used all over the country at that time contained 0.15 to 0.3g of urethane which is a carcinogenic substance, per ampoule. 3) Even the revision of the Pharmaceutical Affairs Law could not prevent cases of drug-induced suffering. I think that all concerned should have a full understanding, receive fair judgement and be encouraged to prevent such mistakes in the future.

Acquired Immunodeficiency Syndrome↗

Comparative blood compatibility of polyether vs polycarbonate urethanes by epifluorescent video microscopy.

The segmented polyether urethanes (PEUs) have been used in implantable medical devices due to excellent mechanical properties, acceptable blood compatibility, and good biostability. However, recent studies demonstrate that the polyether soft segment of PEU is susceptible to oxidative degradation in vivo due to scission of the polyether group. Recently, polycarbonate urethanes (PCUs) having no ether linkage in the soft segment have been developed, and show improved stability against oxidative degradation over PEUs. The current study evaluates blood compatibility of these PCUs in comparison with PEUs using epifluorescent video microscopy (EVM) combined with a parallel plate flow cell. The authors selected two PCUs, Corethane 80A (Corvita Corporation, Miami, FL) and PCU(1560), and two PEUs, Pellethene 2363-80AE (Dow Chemical Japan, Tokyo, Japan) and Tecoflex EG80A (Thermedics, Inc., Woburn, MA), all of which have similar hard segment compositions (MDI or HMDI:1,4-butanediol(BD)) and the same hardness of 80A. The EVM measured the amount of platelet coverage on the surfaces using human whole blood perfused at a wall shear rate of 100/sec for 20 min. Complement activation (C3a) also was measured. Both PEUs, especially Pellethane, showed significantly higher platelet adhesion than the PCUs (p < 0.05). There were no significant differences in platelet adhesion between the two PCUs. As for C3a measurements, Tecoflex showed higher complement activation than the others. Based on these results, it is recommended that PEUs should be replaced by ether free PCUs for use in implantable blood contacting devices such as artificial hearts and pacemaker lead insulators.

Biocompatible Materials↗

Cytotoxicity of urethane dimethacrylate composites before and after aging and leaching.

The in vitro cytotoxicity of urethane dimethacrylate composites cured at different times by visible light and after different aging times and extraction treatments was evaluated using succinic dehydrogenase activity in the mitochondria of a fibroblastic cell line to reflect cell viability. In addition, extractable chemicals associated with cell response were identified. The composite samples were tested untreated, polished, or extracted with water or 75% ethanol-water. Balb/c 3T3 fibroblasts were used as the cell culture system while MTT-formazan production was used as the toxicity parameter. Cell viability was calculated as a percentage of Teflon controls. Identification of the chemicals was measured by extracting the composites with 75% ethanol-water, separating the extract by HPLC, and identifying the fractions with mass spectroscopy. In general, cell viability increased continuously with curing time for differently treated samples at high aging times (288 h) while it decreased when the composites were not aged (0 h). In addition, for 75% ethanol or water-extracted composites, cell viability increased within the first 24 h of aging and reached a plateau after 72 h. Lowest cytotoxicity occurred when the samples were extracted with the 75% ethanol solution. The highest cytotoxic effects were found when the samples were untreated. Slightly reduced cytotoxic effects were seen with polished composites. The results suggest that curing the light-activated composites for a minimum of 150 s and post-curing for 24 h is required to attain comparable biocompatibility with the Teflon control. Removing the oxygen-inhibited layer from these composites decreased the cytotoxicity by 33% while extracting the composites with 75% ethanol-water decreased it by 77%. Chemicals released from the surface accounted for approximately 40% of cellular response while about 60% of the response was due to chemical components released from the bulk. The primary leachable component from the composites was UDMA monomer. Small quantities of 1,6 hexane diol methacrylate, camphoroquinone, and 2,4,6-tritertiarybutyl phenol also were found.

3T3 Cells↗

Phase relations of rhythmic neuronal firing in the supramammillary nucleus and mammillary body to the hippocampal theta activity in urethane anesthetized rats.

Structures in the caudal diencephalon including the posterior hypothalamic nucleus, the supramammillary nucleus (SUM) and the nuclei of the mammillary body (MB) occupy a strategic position in the crossroads of ascending and descending traffic between the brainstem and the limbic forebrain (septum/hippocampus). In this study we analyzed the phase relations of rhythmically discharging SUM/MB cells to hippocampal theta rhythm in urethane anesthetized rats with a dual aim of separating different functional types of SUM and MB neurons and characterizing their coupling to septohippocampal theta oscillators. We found that rhythmically firing neurons in the SUM/MB represent a functionally heterogenous population of cells that are coupled with forebrain theta oscillators at different preferred phases. Based on their phase relations to hippocampal theta four groups of rhythmic SUM/MB cells were identified. Neurons of the first and second groups fired out-of-phase relative to each other and synchronously with the positive (8 degrees +/- 7) or negative peaks (-177 degrees +/- 7) of theta field activity in the hippocampus, recorded above the CA1 pyramidal layer. Cells of the other two groups, also forming out-of-phase counter-parts, fired on the rising (97 degrees +/- 9) or falling segments (-97 degrees +/- 6) of CA1 theta waves. The peaks in the phase distribution histogram were well separated, and the empty zones between them were wider (40-70 degrees) than those comprising the phase data for different groups. The variations of phase values for individual neurons, when tested during several theta epochs, did not exceed the range of a single group. Theta field potentials were also recorded in the SUM/MB and were advanced by one quarter of the cycle (79 degrees +/- 9, range 56-99 degrees) relative to CA1 theta oscillations. The present results indicate that, similar to other theta-generating structures, rhythmically firing neurons can be classified on the basis of their phase relations in the SUM/MB as well. Different classes of SUM/MB neurons might play different roles in generating and/or transmitting theta rhythmic activity of the limbic system.

Anesthetics, Intravenous↗

Distribution and analysis of hippocampal theta-related cells in the pontine region of the urethane-anesthetized rat.

In the present study 99 cells were recorded in the pontine region of urethane-anesthetized rats during: (1) the spontaneous occurrence of hippocampal formation (HPC) theta field activity; (2) sensory-induced (tail pinch) theta field activity; and (3) large amplitude irregular field activity (LIA). Using the criteria of Colom and Bland (Brain Res 1997;422:277-286) for the classification of theta-related cells, 58/99 cells (59%) were involved with changes in activity related to the occurrence of HPC theta field activity, 24/99 (24%) were non-related, and 17/99 (17%) were related to the sensory input (tail pinch). All cells recorded discharged in a tonic, non-rhythmic pattern in relation to the HPC field activity occurring during the three conditions. Of the 58 theta-related cells, 52 (90%) were classified as tonic theta-ON cells and 6 (10%) as tonic theta-OFF cells. There were no clear regional differences in the distribution of cell types. Statistical analysis of the discharge rates of tonic theta-ON cells during spontaneously occurring theta and tail pinch-induced theta (tested on 48 cells) revealed that 22/48 (46%) of these cells discharged at significantly higher rates during the faster theta field frequencies associated with tail pinches while 26/48 (54%) tonic theta-ON cells did not change discharge rate between the spontaneously occurring theta and the tail pinch-induced theta states. In addition, the discharges of 11/52 (21%) tonic theta-ON cells exhibited weak to moderate correlations with the negative peak of HPC theta field activity recorded from the stratum moleculare of the dentate gyrus. Of the 17 cells related to the sensory stimulation (tail pinch), 12 (71%) cells increased discharge rate during the tail pinch and were classified as sensory activated, while 5 (29%) cells decreased discharge rate during the tail pinch and were classified as sensory inactivated. The results supported the following conclusions: (1) the main cells in the pontine region involved with changes in activity related to the occurrence of HPC theta field activity are tonic theta-ON cells and tonic theta-OFF cells; (2) a subpopulation of tonic theta-ON cells coded the increasing intensity of activation of the ascending brainstem HPC synchronizing pathways by an increase in discharge rate; and (3) a smaller population of cells in the rostral pontine region appeared to be related to sensory stimulation, independent of theta-related activity.

Anesthetics, Intravenous↗

Enzyme-labile protecting groups in peptide synthesis: development of glucose- and galactose-derived urethanes.

The development of the tetra-O-acetyl-D-glucopyranosyloxycarbonyl (AGlOC) and tetra-O-acetyl-beta-D-galactopyranosyloxycarbonyl (AGalOC) protecting groups, which are fully enzyme-labile, carbohydrate-derived urethanes, is described. The protected amino acids were easily synthesized and subsequently converted into a series of model dipeptides through classical peptide couplings. Cleavage of an alpha/beta-anomeric mixture of a model AGlOC dipeptide was achieved with a "one-pot" procedure in good yield. To gain a better understanding of the enzymatic deprotection reaction, the AGalOC group was removed through a two step biotransformation (lipase catalyzed deacetylation, followed by beta-galactosidase catalyzed glycosidic bond fragmentation). Under these very mild reaction conditions (aq. buffer pH7.0, 37 degrees C), the desired N-terminal, unprotected dipeptide conjugates were obtained. The methodology was further utilized for the synthesis of an advanced tetrapeptide model system.

Acetylation↗

N-Monosubstituted urethanes of 6-cis-dialkylamino-1,3,3-trimethyl-2-oxabicyclo [2.2.2] octan-5-trans-ols with hypotensive and other activities.

The synthesis of three series of N-monosubstituted urethanes of 6-cis-dialkylamino-1,3,3-trimethyl-2-oxabicyclo [2.2.2] octan-5-transols (IV), (V) and (VI) (dialkylamino = pyrrolidino, piperidino, morpholino) by reaction of the corresponding aminoalcohols with alkyl or aryl isocyanates, is described. A number of compounds (IV) and (V) showed remarkable hypotensive and bradycardic activity in rats, whereas (IV c) showed infiltration anesthesia and (IV n) antiarrhythmic activity in mice comparable to those of lidocaine. Antiacetylcholine activity in vitro is also reported.

Acetylcholine↗

Micronuclei in mouse skin cells following in vivo exposure to benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, chrysene, pyrene and urethane.

Detection of micronuclei (MN) in skin cells from HRA/Skh hairless mice treated with chemical or physical agents may prove informative in qualitative and quantitative studies of skin carcinogenesis. MN induction and cell survival were estimated in cytokinesis-blocked keratinocytes, cultured for 4 days in vitro, after a single topical dose of various organic compounds. Treatment with 2.56 micrograms (10 nmol) 7,12-dimethylbenz[a] anthracene (DMBA) resulted in maximal MN induction in cells removed from skin 12-24 hr after topical administration (79-88 MN/1,000 cells compared with 10-16 MN/1,000 cells in acetone-treated controls). Even in cells removed only 1 hr after DMBA treatment, a significant increase in MN was evident. However, to allow sufficient time for metabolic activation, a sampling time for of 24 hr was adopted for all test substances. Dose-dependent increases in MN were observed with DMBA, benzo[a]pyrene, chrysene, and urethane. Increased numbers of micronucleated cells were detected at the lowest doses administered in the present study (0.128, 0.5, 50, and 50 micrograms, respectively). Although reduced cell recovery occurred following exposure of mice to acetone, pyrene, and other chemicals, there was no evidence that cytotoxicity contributed to MN scored in keratinocytes. Moreover, the probable noncarcinogen, pyrene, failed to induce MN at doses from 2.5 micrograms to 2.5 mg/mouse. These results show that it is possible to assess chemical exposure in skin by measuring cell survival and skin genotoxicity by measuring MN induction in cultured keratinocytes. The available data suggest that MN induction may be a useful indicator of the carcinogenic potential of chemicals applied to the skin.

9,10-Dimethyl-1,2-benzanthracene↗

Induction of DNA damage by urethane in mouse testes: DNA binding and unscheduled DNA synthesis.

The extent and persistence of DNA damage and repair were investigated in mouse spermatogenic cells exposed in vivo to urethane (ethyl carbamate, EC). Adult male mice exposed to [3H]EC at 10-1,000 mg/kg were sacrificed 12 hr later. EC/metabolite binding to liver and testicular DNA and to sperm heads from the vasa deferentia was measured. Other male mice were exposed to EC at 50-750 mg/kg, and unscheduled DNA synthesis (UDS) induction was investigated in early spermatid stages. Similar experiments were conducted with vinyl carbamate (VC; putative EC metabolite) at 10-75 mg/kg. [3H]EC bound to liver and testicular DNA and to whole sperm heads. Testicular DNA binding increased linearly with dose, although binding was at least 2 orders of magnitude lower than with liver DNA. Sperm head binding also increased linearly with dose. Dose response studies with the UDS assay showed that EC and VC induced a small but significant increase of the UDS response in early spermatid stages. However, the induced UDS responses were quite variable and did not consistently increase with the administered dose. To determine the time kinetics of UDS induction, [3H]dThd was injected at various times after treatment with 500 mg/kg of EC or 60 mg/kg of VC. A slight but significant UDS increase was observed 4 hr after treatment with EC but not with VC. Overall, these results suggest that EC metabolites bind to testis DNA and cause low-level DNA damage in mouse spermatogenic cells. This type of DNA damage apparently does not have significant genetic consequences.

Animals↗

A new vascular prosthesis coated with polyamino-acid urethane copolymer (PAU) to enhance endothelialization.

Clinically available synthetic ePTFE vascular grafts frequently fail when used for small-diameter arterial substitution. The lower long-term patency of ePTFE grafts is due mainly to thrombogenicity and poor healing. We developed a new small-diameter (1.5-mm) ePTFE vascular prosthesis coated with polyamino-acid urethane copolymer (PAU) to enhance endothelialization. Coating with PAU made the hydrophobic ePTFE vascular graft hydrophilic. Scanning electron microscopy (SEM) observation showed that PAU was homogeneously coated on the ePTFE graft while maintaining the graft's porous structure. Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectra showed PAU was present on graft inner surfaces. Noncoated and PAU-coated ePTFE vascular grafts were implanted into the rat abdominal aorta and evaluated within 1 week and at 8 weeks after implantation. We evaluated the extent of neoendothelialization by SEM, light microscopy, and immunohistochemical staining. Noncoated grafts showed partial endothelialization at proximal and distal areas of grafts but none at midsection. One-percent PAU-coated grafts showed incomplete neoendothelialization, but endothelial cells were observed in the midsection of grafts. Three-percent PAU-coated ePTFE grafts showed complete endothelialization with typical endothelial cell layers under SEM and histologic observation. Immunohistochemical staining also showed that an endothelial cell lining positively reacted with anti-von Willebrand factor (endothelial cell marker) antibody. We conclude that PAU-coated ePTFE vascular grafts enhance endothelialization.

Amino Acids↗