Membranes made from 4 commercial poly(carbonate urethanes): Carbothane (CB), Chronoflex (CF), Corethane 80A (CT80), and Corethane 55D (CT55), and from 2 poly(ether urethanes): Tecoflex (TF) and Tecothane (TT) were prepared by solution casting and sterilized by either ethylene oxide (EO) or gamma radiation. Their biocompatibility was evaluated in vitro in terms of proliferation, cell viability, and adhesion characteristics of human umbilical veins (HUVEC), monocytes (THP-1), and skin fibroblasts, and by measuring complement activation through the generation of the C3a complex. Their hemocompatibility was determined by measuring the level of radiolabeled platelet, neutrophil, and fibrin adhesion in an ex vivo arteriovenous circuit study in piglets as well as via an in vitro hemolysis test. The results of this study showed no endothelial cell proliferation on any of the materials. The cell viability study revealed that the CB, CF, and TF membranes sterilized by EO maintained the highest percentage of monocyte viability after 72 h of incubation (>70%) while none of the gamma-sterilized membranes displayed any cell viability. The fibroblast adhesion and C3a generation assays revealed that none of the materials supported any cell adhesion or activated complement, regardless of the sterilization method. The hemolysis test also confirmed that the 4 poly(carbonate urethanes) were hemolytic while none of the poly(ether urethanes) were. Finally, the ex vivo study revealed that significantly more platelets adhered to the CB and CT55 membranes while the levels of neutrophil and fibrin deposition were observed to be similar for all 6 materials. In conclusion, the study identified the CF and TF membranes as having superior biocompatibility and hemocompatibility compared to the other polyurethanes.

TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-β-diacetoxy-2-α-benzoyloxy-5-β-20-epoxy-1,13-α-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a novel semisynthetic taxane derivative. Our previous study suggested that TM-2 is a promising antitumor analogue. In this paper, the metabolism of TM-2 was investigated in rats following intravenous administration. Two different types of mass spectrometry-hybrid linear trap quadrupole orbitrap (LTQ-Orbitrap) mass spectrometry and triple-quadrupole tandem (QQQ) mass spectrometry-were employed to acquire structural information of TM-2 metabolites. A total of 17 components were identified as the metabolites of TM-2 in bile, feces, and urine samples. Accurate mass measurement using LC-LTQ-Orbitrap-MS was used to determine the accurate mass data and elemental composition of metabolites thereby confirming the proposed structures of the metabolites. The metabolites proposed were mainly oxidates of TM-2, including methoxy, hydroxyl, dihydroxy, and trihydroxyl analogues. The major metabolic pathway of TM-2 was the hydroxylation of the taxane ring or the lateral chain. These important metabolic data serve as a useful resource to support further research of TM-2.

No abstract

No abstract

No abstract

Ventricles made from segmented polyurethane membranes and used in the fabrication of a totally implantable artificial heart are known to undergo biomaterial-associated calcification. As there is no effective method currently available to prevent such biomaterials from calcifying, a practical solution is to use only materials with a relatively high resistance to calcification, to extend ventricular durability and ensure a longer functional life for the manufactured device. In the present study, an in vitro calcification protocol was used to determine the relative resistance to calcification of six different polyurethanes, namely, Carbothane PC3570A, Chronoflex AR, Corethane 80A, Corethane 55D, Tecoflex EG80A, and Tecothane TT1074A. The results demonstrated that all six polyurethanes did become calcified during the 60-day incubation period in the calcification solution. The degree of calcification was found to be associated with the surface chemistry of the particular polyurethane, with the Tecothane TT1074A exhibiting the highest level. The Corethane 80A and 55D polymers showed a relatively low propensity to calcify. These two membranes can, therefore, be considered as the most appropriate materials for the fabrication of ventricles for a totally implantable artificial heart. In addition, since the calcification occurred primarily at the surface of the membranes, without affecting the bulk microphase structure, the issue of modifying the surface chemistry to reduce the incidence of calcification is discussed.

No abstract

In the development of a new generation of totally implantable artificial hearts and left ventricular assist devices (VADs) for long-term use, the selection of an acceptable material for the fabrication of the ventricles probably represents one of the greatest challenges. Segmented polyether urethanes used to be the material of choice due to their superior flexural performance, acceptable blood compatibility, and ease of processing. However, because they are known to degrade and to be readily permeable to water, they cannot meet the rigorous requirements needed for a new generation of implantable artificial hearts and VADs. Therefore, the objective of the present study was to identify alternative polymeric materials that would be satisfactory for fabricating the ventricles, and in particular, to determine the water permeability through membranes made from four commercial polycarbonate urethanes (Carbothane PC3570A, Chronoflex AR, Corethane 80A, and Corethane 55D) in comparison to those made from two traditional polyether urethanes (Tecoflex EG80A and Tecothane TT-1074A). In addition to determining the rate of water transmission through the six membranes by exposing them to deionized water, saline, and albumin-Krebs solution under pressure and measuring the displacement of liquid by means of a recently developed capillary method, the inherent surface and chemical properties of the six membranes were characterized by SEM, contact angle measurements, FTIR, DSC, and GPC techniques. The results of the study demonstrated that the rate of water transmission through the four polycarbonate urethane membranes was significantly lower than through the two polyether urethanes. In fact the lowest values were recorded with the two Corethane membranes, and the harder type 55D polymer had a lower value (2.7 x 10(-7) g/s cm2) than the softer 80A version (3.3 x 10(-7) g/s cm2). This level of water vapor permeability, which appears to be controlled primarily by a Fickian diffusion mechanism, is between 2 and 4 times lower than that obtained with traditional polyether urethane membranes of equivalent thickness. The superior performance of the polycarbonate urethanes is likely due to the inherently lower chain mobility of the carbonate structure in the soft segment phase. In addition, the study shows that additional impermeability to water vapor can be achieved by selecting a polyurethane polymer with a high hard segment content, an aromatic rather than aliphatic diisocyanate comonomer, and a more hydrophobic surface. The use of a higher molecular weight polyurethane is not necessarily efficacious if the above requirements are not met. As expected by Raoult's Law, the study found that the use of physiological media instead of deionized water further decreases the rate of water vapor transmission. Because none of today's commercial polyurethanes are totally impervious to water vapor transmission, additional work is needed to develop permeable polymers or to apply additional treatments to existing candidates to achieve an acceptable impe...