Clotting Phenomena at the Blood-Polymer Interface and Development of Blood Compatible Polymeric Surfaces

In the past two decades many attempts have been made to relate surface and interfacial parameters with the blood compatibility of polymeric surfaces. It is however doubtful if by a single parameter the behaviour of blood on a surface can be predicted. Two major aspects of blood compatibility - the prevention of platelet adhesion and the deactivation of the intrinsic coagulation system are determined by the measure and nature of competitive blood protein adsorption on the foreign surface. The adhesion of blood platelets is promoted by adsorbed fibrinogen and gamma globulin, while adsorbed albumin inhibits platelet adhesion. Heparinised surfaces do not adsorb fibrin and consequently no adhesion of platelets takes place. Other surfaces with low platelet adhesion are the hydrogels, certain block copolyetherurethanes, polyelectrolyte complexes and biolised proteins. Heparinised surfaces of the cationically bonded type inhibit the intrinsic coagulation as well, however this may be due to unstable coatings and heparin leakage. \ud In the authors laboratory a synthetic heparinoid was prepared with the structure - [CH2 - C(CH3 NHSO3 Na - C(H) COONa - CH2 -]x with Mw = (7.5 /pm 1.0) × 105 and an in vivo anticoagulant activity of 50% of heparin. Its coatings on PVC, using tridodecylmethyl-ammonium chloride as a coupling agent, are stable in plasma and salt solutions and provide surfaces which show negligible platelet adhesion and a strong inhibition of the intrinsic coagulation on contact with blood. Similar results were found with polydimethylsiloxane surfaces coated with this heparinoid

Adsorption of a synthetic heparinoid polyelectrolyte on an ion-exchanging surface

The adsorption of a synthetic heparinoid polyelectrolyte on poly(vinylchloride) previously treated with tridodecylmethylammonium chloride (TDMAC) was studied using radiotracer techniques to provide a more quantitative picture of antithrombogenic surface coatings. 125I-labeled polyelectrolyte was used for overall adsorption measurements. Experiments with 36Cl-labeled TDMAC yielded information on actually adsorbed polyelectrolyte segments in good agreement with existing theory. A large excess of free dangling segments was found. In the presence of NaCl the total adsorption was diminished, although no desorption occurred on treatment of adsorbates with 0.15 M NaCl or blood plasma

Investigations on vinylene carbonate. IV. Radiation induced graft copolymerization of vinylene carbonate and N-vinyl-N-methylacetamide onto polyethylene films

Graft copolymerization of binary mixtures of vinylene carbonate (VCA) and N-vinyl-N-methylacetamide (VIMA) onto low density polyethylene (LDPE) films was studied by the mutual γ-irradiation technique. Sufficient amounts of functionally active VCA groups could be grafted onto the surface and the hydrophilicity of the surface was also improved. The grafting of VCA onto polyethylene films in the binary solutions was found to be promoted by the presence of VIMA, thus showing a positive synergism. The VCA content in the graft copolymers was always higher than in the copolymers obtained by homogeneous copolymerization using the same monomer feed composition. The monomer reactivity ratios, as well as a preferential partitioning of the monomers surrounding the polymeric substrate, were considered to explain the grafting reactions in the binary systems

Investigations on vinylene carbonate. V. Immobilization of alkaline phosphatase onto LDPE films cografted with vinylene carbonate and N-vinyl-N-methylacetamide

Low-density polyethylene (LDPE) films cografted with vinylene carbonate (VCA) and N-vinyl-N-methylacetamide (VIMA) were studied as a matrix for the immobilization of the enzyme alkaline phosphatase (ALP) either by direct fixation or by inserting spacers. When water-soluble alkyldiamines such as diaminoethylene, diaminobutane, diethylenetriamine, and diaminohexane were used as spacers between the matrix and the enzyme, the surface concentration (SC) of the active ALP coupled on the matrix was increased, whereas the effect of the spacer on the SC was dependent on the length of the spacer. Bovine serum albumin (BSA) was preimmobilized onto the LDPE films to provide a better simulation of the biological environment for the enzyme, and the SC of ALP on the matrix was significantly increased by coupling ALP onto the BSA preimmobilized surfaces. Compared to native ALP, some physicochemical properties of ALP could be improved by the covalent immobilization

Coating Membranes for a Sorbent-Based Artificial Liver: Adsorption Characteristics

Techniques are described for the coating of sorbents to be used in an artificial liver support system based on mixed sorbent bed hemoperfusion. Activated charcoal has been coated with cellulose acetate (CA) by solvent evaporation. With Amberlite XAD-4, the Wurster technique was used for coating with CA. XAD-4 has also been coated with a synthetic polyelectrolyte with anticoagulant activity by adsorption and fixation by gamma radiation-induced crosslinking. Activated charcoal, XAD-4, and a cation exchange resin, all in powdered form, were encapsulated in agarose gel beads. Adsorption characteristics onto the sorbents are described. The results are in agreement with a theoretical model presented. In general, adsorption onto XAD-4 is limited by film diffusion. With activated charcoal, pore diffusion limitation is generally observed. Blood compatibility is improved by coatin

Solid-state conformation of copolymers of ß-benzyl-L-aspartate with L-alanine, L-leucine, L-valine, γ-benzyl-L-glutamate, or ε-carbobenzoxy-L-lysine

The solid-state conformation of copolymers of ß-benzyl-L-aspartate [L-Asp(OBzl)] with L-leucine (L-Leu), L-alanine (L-Ala), L-valine (L-Val), γ-benzyl-L-glutamate [L-Glu(OBzl)], or ε-carbobenzoxy-L-lysine (Cbz-L-Lys) has been studied by ir spectroscopy and circular dichroism (CD). The ir spectra in the region of the amide I and II bands and in the region of 700-250 cm-1 have been determined. The results from the ir studies are in good agreement with data obtained by CD experiments. Incorporation of the amino acid residues mentioned above into poly[L-Asp(OBzl)] induces a change from the left-handed into the right-handed α-helix. This conformational change for the poly[L-Asp(OBzl)] copolymers was observed in the following composition ranges: L-Leu, 0-15 mol %; L-Ala, 0-32 mol %; L-Val, 0-8 mol %; L-Glu(OBzl), 3-10 mol %; and Cbz-L-Lys, 0-9 mol %

Polyethers for biomedical applications. Polymerization of propylene oxide by organozinc/organotin catalysts

The polymerization of propylene oxide to obtain a high-molecular-weight polymer with an atactic structure required for the application as artificial blood vessels was investigated using combinations of organozinc and organotin compounds as catalyst. The composition of the most active catalyst, resulting from the reaction of diphenyltin sulfide with bis(3-dimethyl-aminopropyl)zinc, was found to be R(C6H5)2Sn(SZn)2R with R = (CH2)3N(CH3)2. Using this catalyst, an anionic coordination polymerization was observed with neither stereoselectivity nor living type or cationic features. At low catalyst concentration (0,03 mol-% Zn) a high-molecular-weight poly(propylene oxide) (PPOX) was obtained in 80-90% yield ([bar M ]w = 500000; 40% isotactic). Lowering of the catalyst concentration and increasing the polymerization temperature changed the kinetics and the stereochemistry of the polymerization leading to polymers of lower molecular weight and to a decrease in the isotactic PPOX fraction to 20%, probably due to an association of the catalytic species

Effect of methyl groups on the thermal properties of polyesters from methyl substituted 1,4-butanediols and 4,4'-biphenyldicarboxylic acid

Results are reported on the effect of lateral methyl groups on the thermal properties of a series of polyesters prepared from diethyl 4,4-biphenyldicarboxylate and various methyl substituted 1,4-butanediols. The diols were 1,4-butanediol; 2-methyl-1,4-butanediol; 2,2-dimethyl-1,4-butanediol; 2,3-dimethyl-1,4-butanediol; 2,2,3-trimethyl-1,4-butanediol; and 2,2,3,3-tetramethyl-1,4-butanediol. Apart from the tetramethyl derivatve, the transition temperatures of the methyl substituted polyesters were lower with respect of the unsubstituted polyester. On the basis of polarized photomicrographs, a smectic A mesophase was found for the unsubstituted polyester, whereas a nematic mesophase was observed for the 2-methyl substituted polyster. The 2,2-dimethyl, 2,3-dimethyl, and the 2,2,3-trimethyl substituted polyesters showed no liquid crystalline behavior. The 2,2,3,3-tetramethyl derivative displayed a birefringent melt phase although the DSC measurements were not unambiguous. A copolyester based on diethyl 4,4-biphenyldicarboxylate, 1,4-butanediol, and 2,2,3,3-tetramethyl-1,4-butanediol showed a broad nematic mesophase. Further evidence for the nematic mesophase of this copolyester and the 2-methyl substituted polyester was provided by dynamic rheological experiments. Based on thermogravimetric analysis, it was concluded that the thermal stability was affected only when four methyl side groups were present in the spacer

Investigations on vinylene carbonate, 2. Copolymerization with N-vinyl-2-pyrrolidone and ethyl vinyl ether

Functional monomers and polymers have received considerable attention in recent years, especially in the biomedical field. In this respect, poly(viny1ene carbonate) is very interesting, because the reactive carbonate groups offer the possibility of coupling with bioactive compounds containing amino groups, e. g. proteins or enzymes. Copolymerization of vinylene carbonate with other vinyl monomers will affect the amount of carbonate groups as well as other properties of the copolymers. In a previous paper we described the preparation and properties of poly(viny1ene carbonate) I), and this paper reports the copolymerization of vinylene carbonate with N-vinyl-2-pyrrolidone and with ethyl vinyl ether

Pivalolactone, 1 interchange reactions with polypivalolactone

Ester interchange, alcoholysis, and acidolysis of polypivalolactone (PPVL) were studied by melting PPVL with bisphenol diacetates, 1, 4-butanediol, or aromatic diacids. Interchange of PPVL with the diacetates and the diol occured readily, in particular in the presence of a titanium catalyst. Melting PPVL with 10 mol-% of bisphenol-Adiacetate in the presence of 0,5 wt.% tetrabutylorthotitanate resulted in an incorporation of 33% of the diacetate in the polymer chains, whereas the logarithmic viscosity number decreased by 81%. The ester interchange was suggested to proceed by an initial cleavage of ester bonds in the polymer chain of PPVL, resulting in the formation of shorter chains, followed by a reaction between the newly formed ester end-groups and initially present hydroxyl chain ends. The acidolysis of PPVL with the diacids proved to be less effective; in the case of the acidolysis of PPVL with 10 mol-% isophthalic acid, less than 1% of the diacid was incorporated in the polymer chains and a decrease in the logarithmic viscosity number of only 22% was found. Both the high stability of the ester bond in PPVL towards acids in general and the heterogeneity of these systems were supposed to cause the behaviour of PPVL with respect to acidolysis. The results concerning the interchange reactions with PPVL were compared with studies on other polyesters