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A new π-conjugated charge-transfer-type copolymer of electron-donating thiophene and electron-accepting quinoxaline was prepared by organometallic polycondensation. The polymer was soluble in organic solvents such as tetrahydrofuran, and showed a UV-vis peak at long wavelengths of 598 nm in chloroform and 629 nm in the film. Its film exhibited a χ (3) peak in the resonance region with a χ (3) value comparable to that of regioregular head-to-tail poly(3-hexylthiophene-2,3-diyl).

Self-assembled monolayers of alkylsiloxanes supported on polydimethyl siloxane (PDMS) rubber were used as model systems to study the relation between blood compatibility and surface chemistry. The inner lumen of PDMS tubes was first treated with an oxygen plasma. The resultant oxidized surfaces were postderivatized by reacting them with alkyltrichlorosilanes to form the monolayer films. The chemical properties of the monolayers were controlled by varying the head-group chemical compositions. Surface derivatization was verified using variable-angle X-ray photoelectron spectroscopy (XPS or ESCA). Blood compatibility was evaluated using a canine ex vivo arteriovenous series shunt model. Surfaces grafted with hydrophobic head-groups as -CH3 and -CF3 had significantly lower platelet and fibrinogen deposition than the surfaces composed of hydrophilic groups such as -CO2CH3, -(CH2CH2O)3COCH3, and -(OCH2CH2)3OH. © 1995 John Wiley & Sons, Inc.

The acute blood-contacting properties of five silicone-containing elastomers and a poly(vinyl alcohol) coated silicone elastomer were assessed using a canine ex vivo shunt model. The silicone-containing elastomers studied included two thermoset amorphous silica reinforced dimethyl methylvinyl siloxane-based polymers which were extruded as Silastic® RX-50 Medical Grade Tubing (RX-50) and Silastic® Medical Grade Tubing H.P. (HP). They also included three experimental thermoplastic silicone-urea urethane copolymers received as X7-4074 (SP-1), X7-4037 (SP-2), and X7-4943 (SP-3). The RX-50 tubing material showed less thrombus deposition compared to the silicone-urea urethane copolymers. This suggests that the blood-contacting response of a silicone elastomer is strongly affected by the incorporation of the urea urethane segments. Among the silicone-urea urethane copolymers, the SP-3 material showed higher levels of platelet and fibrinogen deposition than the SP-1 and SP-2 materials, whereas the SP-1 and SP-2 samples had similar levels of deposition. These results indicate that the blood-contacting properties of the silicone-urea urethane copolymers were influenced more by the molecular weight of the polydimethylsiloxane than by the type of diol used in the urea urethane segments. The maximal platelet deposition on the poly vinyl alcohol-coated silicone was approximately an order of magnitude greater than those on the silicone-containing elastomers indicating that the PVA coating was more thrombogenic.

In an attempt to improve endothelial cell adhesion and growth on a polyurethane copolymer, cell adhesive RGD-containing peptides were grafted to the polymer backbone. Two peptide grafting reaction schemes, including one-step and two-step approaches, were developed. Amino acid analysis confirmed that the two-step approach had a higher peptide coupling efficiency. The two-step reaction scheme was utilized to prepare GRGDSY, GRGDVY and GRGESY (inactive control) peptide grafted polyurethanes with two different peptide densities (100 and 250 μmol/g polymer). In-vitro endothelial cell adhesion experiments showed that, without the presence of serum in culture medium, the GRGDSY- and GRGDVY-grafted polyurethanes dramatically enhanced cell attachment and spreading. Increasing the peptide density from 100 to 250 jimol/g polymer for the GRGDSY-and GRGDVY-grafted polyurethanes resulted in an increase in cell attachment. Similar trends were observed in endothelial cell growth studies using culture medium containing serum and growth supplement.

Peptides based on cell-adhesive regions of fibronectin, Arg-Gly-Asp-Ser (RGDS), and vitronectin, Arg-Gly-Asp-Val (RGDV), were covalently bound to a polyurethane backbone via amide bonds. Nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR) spectroscopies were used to monitor the reactions. The amount of grafted peptide was determined by amino acid analysis. X-ray photoelectron spectroscopy (XPS) suggested the presence of the grafted peptide at the polymer-air interface in vacuo. Dynamic contact angle analysis showed that, in water, the peptide-grafted polyurethane surfaces were more polar than the underivatized polyurethane indicating enrichment of peptide groups at the surface. The attachment and spreading of human umbilical vein endothelial cells (HUVECs) on the underivatized and peptide-grafted polyurethanes was investigated. The GRGDSY- and GRGDVY-grafted substrates supported cell adhesion and spreading even without serum in the culture medium. The GRGDVY-grafted substrate supported a larger number of adherent cells and a higher extent of cell spreading than the GRGDSY-grafted substrate. These RGD-containing peptide-grafted polyurethane copolymers may be useful in providing an easily prepared celladhesive substrate for various biomaterial applications.

Polyurethanes which are grafted with propyl sulphonate functionality have excellent blood-contacting properties. In a canine ex vivo series shunt experiment, very low platelet deposition was observed on these materials and those platelets which were adherent remained unspread. In contrast to this, large amounts of fibrinogen, of the order of a monolayer or greater, were deposited on these surfaces in this ex vivo experiment. This led to the hypothesis that perhaps the deposited fibrinogen did not retain its platelet-adhesive activity. In this paper, we investigate the possibility that these materials exert their antithrombotic effects through the adsorbed protein layer. Protein adsorption kinetics and isotherms on these sulphonated polyurethanes are determined. Multilayer protein adsorption or absorption into the hydrogel-like materials is found for each of the proteins studied, and the greatest amounts of protein are seen on the most highly sulphonated polyurethanes. Further, the blood-contacting response of these materials is investigated after pre-conditioning with either fibrinogen, fibronectin or albumin. When these materials are pre-adsorbed with either fibrinogen or fibronectin, a very thrombogenic response was observed, which suggests that the platelet-adhesive activity of these proteins is not being reduced. Pre-adsorption of albumin did not improve the thromboresistance of these surfaces.

Variable take-off angle and cold-stage ESCA measurements were utilized to analyze the surface composition of five polyurethane block copolymers. The polymers studied included a PTMO-polyurethane control, a carboxylated version of the control polyurethane, and three different peptide grafted (GRGESY, GRGDSY, and GRGDVY) polyurethanes. On dry samples the nitrogen signal detected using ESCA decreased with increasing take-off angle (i.e. as the specimen was probed closer to the surface) for all five polymers. This was believed to be due to the depletion of nitrogen-containing urethane hard segments at the surface. For all five polymers, the surface nitrogen concentration, associated with the hard segment, increased upon hydration. A greater increase of nitrogen concentration was observed for the peptide grafted polymers which suggests that grafting of the hydrophilic peptides to the polyurethane augments the hard segment enrichment at the surface upon hydration. Upon dehydration, the nitrogen concentration decreased for all five polymers suggesting migration of the more hydrophobic PTMO soft segment to the surface. In vitro endothelial cell adhesion showed an increase of cell attachment on prehydrated RGD-containing peptide grafted polyurethanes, but not on the other polymers. This result suggests an enhancement of peptide density at the aqueous interface, in good agreement with the ESCA studies.

The synthesis of a novel polyurethane block co-polymer containing a covalently attached, well-oriented RGD (Arg-Gly-Asp) peptide was explored. A poly(tetramethylene oxide) (PTMO)-based polyurethane was synthesized, and a bimolecular nucleophilic substitution reaction was then employed to incorporate ethyl carboxylate groups onto the polymer backbone (i.e. carboxylated polyurethane). Elemental analysis was used to determine the extent of carboxylation. The hexapeptide H-Gly-Arg-Gly-Asp-Ser-Tyr-OH was coupled to the carboxylated polyurethane via the formation of an amide bond. The attachment of the peptide was controlled by a protection-deprotection scheme. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies were used to monitor the reactions. Sakaguchi assay and amino acid analysis confirmed that the RGD-containing peptide was successfully grafted onto the carboxylated polyurethane. This reaction scheme provides a new route for grafting end-linked, bioactive peptides onto polyurethanes.

Synthesis of novel polyurethane copolymers containing covalently attached, well-oriented Arg-Gly-Asp (RGD) peptides was explored. A poly(tetramethylene oxide) based polyurethane was synthesized, and a bimolecular nucleophilic substitution reaction was then employed to incorporate ethyl carboxylate groups onto the polymer backbone. Cell-adhesive peptides Gly-Arg-Gly-Asp-Ser-Tyr (GRGDSY) and Gly-Arg-Gly-Asp-Val-Tyr (GRGDVY) were covalently bound to the polyurethane backbone via the formation of amide bonds. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies were used to monitor the reactions. The amount of grafted peptide was determined by amino acid analysis. Electron spectroscopy for Chemical Analysis (ESCA) suggested the presence of the grafted peptide at the polymer-air interface in vacuo. Dynamic contact angle analysis showed that, in water, the peptide-grafted polyurethane surfaces were more polar than the underivatized polyurethane. The attachment and spreading of human umbilical vein endothelial cells (HUVECs) on the underivatized and peptide-grafted polyurethanes was investigated. The GRGDSY-and GRGDVY-grafted substrates supported cell adhesion and spreading even without serum in culture medium. The GRGDVYgrafted substrate supported a larger number of adherent cells and a higher extent of cell spreading than the GRGDSY-grafted substrate. These RGD-containing peptide grafted polyurethane copolymers may be useful in providing an easily prepared cell-adhesive substrate for various biomaterial applications.