Timothy G. Grasel

Surface properties and blood compatibility of polyurethaneureas.

A series of polyurethaneureas of varying soft segment type and hard/soft segment ratio were synthesized, and their bulk and surface properties evaluated. A canine ex vivo arteriovenous series shunt was used to monitor initial thrombus deposition. Significant levels of surface hard segment components are apparent in these materials. Polymers with poly(tetramethylene oxide) and poly(propylene oxide) soft segments showed blood compatibility variations with changes in hard/soft segment ratios: the more well-phase-separated materials showing lower platelet and fibrinogen deposition levels. Those trends apparent in polymers synthesized with poly(dimethylsiloxane) or poly(ethylene oxide) soft segments, but poly(dimethylsiloxane)-based materials showed higher levels of thrombus deposition than the poly(ethylene oxide)-based polymers.

Bulk, surface, and blood-contacting properties of polyetherurethanes modified with polyethylene oxide

The bulk, surface, and blood-contacting properties of a series of polyether polyurethanes based on polyethylene oxide (PEO) (MW = 1450), polytetramethylene oxide (PTMO) (MW = 1000), and mixed PEO/PTMO soft segments were evaluated. The effect of varying the weight percentage of PEO, and thus the overall polarity of the mixed soft segment phase, was investigated. Two polymer blends prepared from a PTMO-based and a PEO-based polyurethane were also studied. Differential scanning calorimetry (DSC) and dynamic mechanical analysis indicated that the polyurethanes based on either the PEO or the PTMO soft segments are relatively phase mixed. The degree of phase mixing in the polymers increased with increasing weight fraction of PEO. As expected, water absorption and the hydrophilicity of the polymer increased with increasing PEO soft segment content. In vacuum, the PEO-rich polymers have a lower concentration of soft segment at the surface, possibly due to the migration of the polar PEO segments away from the polymer/vacuum interface. The blood-contacting results indicated that the higher PEO-containing polymers were more thrombogenic than the pure PTMO-based polyurethane. A threshold concentration of PEO in the polyurethane appeared to be required before the blood-contacting properties were significantly affected.

Albumin adsorption on alksyi chain derivatized polyurettianes: II. The effect of alkyl chain length

Linear alkyl chains containing 2, 10 and 18 carbon atoms were grafted to 10% of the urethane nitrogens in a polyether-polyurethane. The polyurethane was synthesized from methylene bis(p-phenyl isocyanate), 1,4-butanediol, and polytetramethylene oxide of 1000 molecular weight in a molar ratio of 3/2/1. Fourier transform infrared spectroscopy and attenuated total reflectance optics were used to study the adsorption of 5.0 mg/ml human serum albumin (HSA) at 37 degrees C to the derivatized and non-derivatized polymers. Both delipidized HSA and HSA containing 6.5 mol stearic acid per mol of albumin were used to study the effect of chain length upon the initial adsorption rate, the total amount adsorbed in 1 h, and the desorption rate. The initial adsorption rates revealed that non-specific adsorption was similar upon all four polymers. An increase in initial adsorption rate upon the C-18 derivatized polymer was attributed to a specific binding interaction between the HSA and the grafted alkyl chains. The conformational stability of the HSA also affected the adsorption rate. The total amount adsorbed after 1 h decreased as the alkyl chain length increased from 2 to 18 methylene groups. The desorption rate decreased in magnitude as the alkyl chain length increased from C-2 to C-18. These results support a hypothesis that alkyl chain length influences the interaction between albumin and an alkylated polymer system.

Bulk, surface and blood-contacting properties of polyether polyurethanes modified with polydimetnylsiloxane macroglycols

The bulk, surface and blood-contacting properties of a series of polyether polyurethanes, modified with three different polydimethylsiloxane (PDMS) macroglycol segments, were evaluated. The PDMS oligomers were terminated with hydroxy-tipped end groups of varying polarity. The effect of substituting the polytetramethylene oxide (PTMO) soft segment of a base polyurethane with 5 and 15 wt% of these PDMS-containing polyols was investigated. The ultimate tensile strength and elongation at break appeared to be the bulk properties most significantly affected by the addition of the PDMS-containing polyols. Underwater contact angle data indicate that the block copolymer surface became more hydrophilic with increasing PDMS content. In a vacuum, as determined from the ESCA data, the relatively non-polar PDMS soft segments preferentially oriented at the surface with increasing PDMS incorporation. Despite the variation in the surface properties, the blood compatibility of these polymers was not significantly affected by the addition of the PDMS-containing polyols.

Properties of extruded poly(tetramethylene oxide) Polyurethane block copolymers for blood-contacting applications

The bulk and surface properties and blood compatibility of a series of polyurethanes based on methylene bis(p-phenyl isocyanate), 1,4-butanediol, and poly(tetramethylene oxide) of molecular weight 1000 were studied. The hard-to-soft segment ratio of these multiphase polymers was varied, and the effect of substituting a poly(dimethylsiloxane)-containing polyol in place of 5% of the polyether soft segment was studied. Bulk properties such as tensile strength and modulus increased with hard segment content, as did surface wettability and ESCA nitrogen content. However, blood compatibility measured by a canine ex vivo blood-contacting experiment was not found to vary with hard/soft segment ratio. The addition of the silicone-containing polyol did not significantly lower the surface wettability, although ESCA-measured silicon content increased and physical properties were unfavourably affected by the incorporation of this co-soft segment. Incorporation of the siloxane-containing component resulted in increased platelet adhesion and fibrinogen deposition at most blood contact times in comparison with the other polyurethanes.

Acute and chronic canine ex vivo blood interactions with NHLBI-DTB Primary Reference Materials

Thrombus deposition was measured on NHLBI-DTB Primary Reference Material polyethylene (PRM-PE) and polydimethylsiloxane (PRM-SR) and their commercially available counterparts, surgical grade Intramedic polyethylene and Dow Corning Silastic. Canine blood-contacting experiments evaluating short-term (up to 60 min) and longer-term (up to 24 h) thrombus deposition were used to quantitate adherent platelets on the lumenal surface of test materials ex vivo. A similar pattern of thrombus deposition and detachment was observed for all materials in both acute and chronic blood contact. Although differences in the wall shear rates affected the absolute numbers of adherent platelets, the relative levels of thrombus deposition showed similarities between the two experiments, with the polyethylene materials as a group showing slightly less deposition than the silicone rubber materials. The PRM-PE showed the least thrombus deposition at extended exposure to blood. The PRM-SR showed the most thrombus deposition in the acute term. The overall similarity in blood compatibility and surface properties indicates the need for the inclusion of less thromboresistant and more polar reference materials.

Methods of assessment of thrombosis ex vivo.

Both in vivo and ex vivo techniques have been used as a means of evaluating the blood compatibility of polymeric biomaterials. This review compares the advantages and disadvantages of these two techniques and emphasizes the role ex vivo techniques have had in the analysis of blood-materials interactions. Several results from recent canine ex vivo studies will also be reviewed. Ex vivo systems can be classified as being either “open” or “closed.” In closed systems, the blood returns to the animal after it has passed through the test chamber or shunt. In open systems, the blood is either analyzed further or discarded without being returned to the animal. Open ex vivo systems are typically based upon either the Dudley clotting time test or upon flow through a test chamber under controlled conditions. The most common closed system configurations are arterio-venous (A-V) shunts or test chambers.

Characterization of Polyurethanes for Blood-Contacting Applications

Segmented polyurethanes are widely used in commercial and experimental blood-contacting applications which include vascular prostheses, blood filters, catheters, insulation for pacemaker leads, heart valves, cardiac assist devices, and chambers for artificial hearts. The use of this family of polymers for such applications is due to the physiological acceptability, relatively good blood tolerability, relative stability over extended implant periods, and excellent physical and mechanical properties that are exhibited by these materials1.

Blood material interactions: Ex vivo investigations of polyurethanes

A canine ex vivo series shunt was utilized to evaluate short-term blood compatibility of polyurethane block copolymers. The series shunt allows the evaluation of up to ten different materials simultaneously. Deposition of radiolabeled platelets and fibrinogen is quantified and used as a measure of thrombogenicity. The canine ex vivo experiment has been implemented in investigations of the roles of many aspects of polymer surface chemistry in platelet-surface and protein-surface interactions. This paper reviews some significant, recent results. The extent of microphase separation in polyurethane block copolymers has been found to affect surface properties and platelet-surface interactions. In addition, derivatization strategies for polyurethanes have been developed that enhance the specific adsorption of albumin, a surface passivating protein, and affect thrombogenicity as measured in the canine ex vivo model.

Ionic Polyurethanes: Surface and Blood-Contacting Properties

Sulfonated polyetherurethanes, synthesized by the substitution of 0, 5, 10, 15, and 20% of the urethane nitrogens with propane sultone, were evaluated in this study. The water absorption properties are dramatically affected by the sulfonate content. The surface properties are also found to be influenced by the percentage of sulfonate incorporation. The blood-contacting properties, as determined by both an acute and chronic canine ex vivo experiment, show increased thromboresistance with increased propyl sulfonate incorporation. A unique characteristic of the highly sulfonated polymers is the negligible platelet activation and spreading observed using scanning electron microscopy.