Blood Compatibility Properties Research Articles

Structure and properties of passivating titanium oxide films fabricated by DC plasma oxidation

Titanium oxide layers have been synthesized on commercially pure titanium and TiN using direct current plasma oxidation. X-ray diffraction analyses reveal that the titanium oxide layers have the rutile structures. Micro-hardness, nano-hardness test, ball-on-plate wear experiment, scratch adhesion test and platelet adhesion investigation were conducted to evaluate the mechanical properties and blood compatibility of the titanium oxide layers. The results show that the commercial purified titanium sample micro-hardness increased by approximately 70% and the TiN sample micro-hardness increased by approximately 30% after plasma oxidation. It is believed that the increase in the film hardness is due to the development of TiO 2 phases. The nano-hardness of titanium oxide layer reached 11 GPa. The wear resistance of the titanium oxide layer increased by a factor of 200 in Hank's solution. The adhesion strength between the titanium oxide layer and titanium matrix was as high as 25 N. Our results thus indicate that titanium oxide layers fabricated by this method have good blood compatibility and mechanical properties.

Change and stabilization of the amyloid-β(1–40) secondary structure by fluorocompounds

The misfolding of the amyloid peptide, which is the result of a well-known α-to-β transition, causes neurodegenerative disorder. Fluorinated alcohols have been described in the literature as potent solvents which can refold the β-conformation. The present studies demonstrate the effectiveness of differently fluorinated alcohols for the β-to-α refolding process on fibrillar aggregated amyloid β(1–40). The regenerated helical structure is shown to be maintained in the absence of the fluoroalcohols, a behaviour which was found to contrast with immunoglobulin. We interpret this difference on the basis of the hydrophilic/hydrophobic domains in the amyloid sequence and present some speculations regarding the free-energy levels of the folded states of both proteins. The effect of the –CF 3 group on the observed conformational changes is interpreted as a result of alterations of the hydration shell of the peptides. Moreover, based on the results achieved with fluoroalcohols, we have used novel fluorinated amphiphiles possessing blood-compatibility properties and studied their effect on amyloid β(1–40). First results point in the direction of a β-to-α transition. Therefore, the use of fluorine groups in the development of new drugs is considered a new possibility requiring further investigation for the prevention of amyloidosis.

Semi‐interpenetrating polymer networks composed of biocompatible phospholipid polymer and segmented polyurethane

2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers, which have excellent biocompatibility, have been receiving increasing attention in biomedical and bioengineering fields; however, the mechanical strength of the hydrated MPC polymers is not sufficient for use in these fields as a bulk material. Therefore, we hypothesized that a novel material might be realized by reinforcing the MPC polymer network with segmented polyurethane (SPU). Semi-interpenetrating polymer networks (IPNs) composed of crosslinked MPC polymer and SPU were prepared. The mechanical properties of the IPN membrane were significantly improved compared with those of the MPC polymer membrane. Three-dimensional polymer networks of the MPC polymer in the IPNs were observed after solvent extraction of SPU. An X-ray photoelectron spectrum analysis revealed that the MPC units were exposed on the IPN surface. When the IPN was alternately soaked in water and ethanol, the swelling ratio was found to be completely reversible and no disintegration of the network structure was observed. The permeation coefficient of 1,4-di(2-hydroxyethoxy)benzene through the IPN membrane was 1.11 × 10−7 cm−2s−1. The amount of adsorbed protein and the number of adherent platelets on the IPN membrane were effectively reduced compared with those on SPU. We concluded that IPNs composed of the MPC polymer and SPU are a new bulk biomaterial, which possesses both blood compatibility and good mechanical properties. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 52, 701–708, 2000.

Semi-interpenetrating polymer networks composed of biocompatible phospholipid polymer and segmented polyurethane

2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers, which have excellent biocompatibility, have been receiving increasing attention in biomedical and bioengineering fields; however, the mechanical strength of the hydrated MPC polymers is not sufficient for use in these fields as a bulk material. Therefore, we hypothesized that a novel material might be realized by reinforcing the MPC polymer network with segmented polyurethane (SPU). Semi-interpenetrating polymer networks (IPNs) composed of crosslinked MPC polymer and SPU were prepared. The mechanical properties of the IPN membrane were significantly improved compared with those of the MPC polymer membrane. Three-dimensional polymer networks of the MPC polymer in the IPNs were observed after solvent extraction of SPU. An X-ray photoelectron spectrum analysis revealed that the MPC units were exposed on the IPN surface. When the IPN was alternately soaked in water and ethanol, the swelling ratio was found to be completely reversible and no disintegration of the network structure was observed. The permeation coefficient of 1, 4-di(2-hydroxyethoxy)benzene through the IPN membrane was 1.11 x 10(-7) cm(-2)s(-1). The amount of adsorbed protein and the number of adherent platelets on the IPN membrane were effectively reduced compared with those on SPU. We concluded that IPNs composed of the MPC polymer and SPU are a new bulk biomaterial, which possesses both blood compatibility and good mechanical properties.

Inhibition of the plasma contact activation system of immobilized heparin: Relation to surface density of functional antithrombin binding sites

End-point immobilization of heparin to artificial materials gives rise to a surface that prevents triggering of the plasma contact activation system and, presumably as a result thereof, generally has thrombo-resistant properties. The present investigation was undertaken to determine what density of immobilized heparin molecules expressing functionally intact antithrombin binding sites is required to achieve these blood compatible properties. Six different heparin surfaces were prepared on polyethylene tubing and studied in contact with human plasma. The content of bound heparin was the same on all surfaces while the densities of antithrombin binding sites ranged from 1 to 28 pmol/cm2. The surfaces expressing 4 pmol/cm2 or more of specific anti-thrombin binding sites generated no measurable enzymatic activity in contact with plasma, either on the exposed surfaces or in the plasma phases. Below this level, the degree of activation gradually increased with decreasing densities, and in parallel the thrombo-resistant properties deteriorated. Addition of heparin to the plasma phase reduced the capacity of the heparin surfaces to bind antithrombin, leading to a diminished ability of the surfaces to prevent contact activation. This finding supports the hypothesis that antithrombin is the critical coagulation inhibitor for the suppression of contact activation on end-point immobilized heparin. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 37–42, 1997.

Inhibition of the plasma contact activation system of immobilized heparin: Relation to surface density of functional antithrombin binding sites

End-point immobilization of heparin to artificial materials gives rise to a surface that prevents triggering of the plasma contact activation system and, presumably as a result thereof, generally has thrombo-resistant properties. The present investigation was undertaken to determine what density of immobilized heparin molecules expressing functionally intact antithrombin binding sites is required to achieve these blood compatible properties. Six different heparin surfaces were prepared on polyethylene tubing and studied in contact with human plasma. The content of bound heparin was the same on all surfaces while the densities of antithrombin binding sites ranged from 1 to 28 pmol/cm2. The surfaces expressing 4 pmol/cm2 or more of specific antithrombin binding sites generated no measurable enzymatic activity in contact with plasma, either on the exposed surfaces or in the plasma phases. Below this level, the degree of activation gradually increased with decreasing densities, and in parallel the thrombo-resistant properties deteriorated. Addition of heparin to the plasma phase reduced the capacity of the heparin surfaces to bind antithrombin, leading to a diminished ability of the surfaces to prevent contact activation. This finding supports the hypothesis that antithrombin is the critical coagulation inhibitor for the suppression of contact activation on end-point immobilized heparin.

Blood compatibility and biodegradability of partially N-acylated chitosan derivatives

Chitosan was selectively N-acylated with various carboxylic anhydrides, e.g. acetic, propionic, nbutyric, n-valeric and n-hexanoic anhydrides, in the presence of methanol. The degree of N-acylation of about 20–50% was obtainable without occurrence of gelation by using carboxylic anhydrides of 0.3–1.2 mol per glucosamine residue. In vitro blood compatibility tests of N-acyl chitosans were performed by rheological measurement, blood clotting test and scanning electron microscopic observation for human blood and plasma protein. The rheological measurement of coagulation of plasma protein, considering the shear flow effect of blood, gave precise and quantitative results compared with other methods. N-Acyl chitosans showed more blood compatible properties than N-acetyl chitosan and, in particular, N-hexanoyl chitosan was the most blood compatible. Enzymatic degradation was also investigated by adding a lysozyme solution to the N-acyl chitosan solution and film, incubating at 37 °C. N-Acyl chitosans had as high a susceptibility to lysozyme as N-acetyl chitosans. It was considered that the amount of derivatized groups and the physical form of N-acyl chitosans contributed to biodegradability. The molecular weight ( M ̄ W ) of the material liberated from the N-acyl chitosan film by the action of lysozyme was 2 × 10 4−10 × 10 4.

Advances of Adsorbents for Hemoperfusion in China

Activated charcoal with various coating materials were screened and tested as adsorbents in hemoperfusion. Among them silicon rubber polyurethane, crosslinked agrose, polyvinyl acetate, polyhydroxy ethyl methacrylate showed good blood compatible properties. Various types of resins and carbonized resins with different functional groups, and structures were tested for the adsorption of small molecules i.e. creatinine, barbiturates, middle molecules i.e. VitB12, inulin, cytochrome C and large molecules i.e. unconjugated bilirubin. High adsorption capacities were obtained and uncoated carbonized resins showed satisfactory blood compatible properties. NK-107 a macroporous, non-coated resin is now being manufactured and successfully used clinically on patients for acute detoxification of hypnotic drugs. Polysaccharide dialdehyde and polystyrene derivatives etc. were used for the removal of urea, ammonia, potassium and phosphorus. DNA immune adsorbents were prepared for systemic lupus erythematosus therapy.

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

Thrombus deposition was measured on NHLBI-DTB Primary Beference Material polyethylene (PRM-PE) and polydimethylsiloxane (PRM-SR) and their commercially available counterparts, surgical grade Intramedic polyethylene Tm and Dow Corning Silastic Tm . 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 PBM-PE showed the least thrombus deposition at extended exposure to blood. The PBM-SB 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.

Synthesis and characterization of poly(dimethylsiloxane)-poly(ethylene oxide)-heparin CBABC type block copolymers

Heparin and poly(ethylene oxide) were coupled to a central anchoring block of poly(dimethylsiloxane) in order to investigate its blood compatible properties. Diamino telechelic poly(dimethylsiloxane) (PDMS-(NH2)2, Mw = 20,000) was first modified to isocyanate functionalities using toluene 2,4-diisocyanate. This modified PDMS was then coupled to diamino-telechelic poly(ethylene oxide) (PEO-(NH2)2, Mw = 2000, 4000, 6000) to create BAB type copolymers having terminal free amino groups. These amino groups were covalently coupled to heparin containing terminal aldehyde groups using sodium cyanoborohydride to yield a bioactive, CBABC type block copolymer. The physical characterization of these copolymers was performed with IR, NMR, sulphur elemental analysis, Wilhelmy plate contact angle, and differential scanning calorimetry (DSC). CBABC block copolymer surfaces demonstrated heparin bioactivity in in vitro evaluation, and improved nonthrombogenic properties during ex vivo A-A shunt experiments.

The ability of sephadex to activate human complement is suppressed in specifically substituted functional sephadex derivatives

The capacity of Sephadex and of chemically substituted Sephadex derivatives to activate human complement was examined by incubating polymer particles in normal human serum (NHS) under conditions that allow classical and/or alternative pathway activation, and by determining complement consumption or generation of C3a antigen in serum. Sephadex was found to activate complement in NHS, mainly through the alternative pathway. The complement-activating capacity of Sephadex was directly related to the surface area of polymer that could interact with serum. Substitution of hydroxyl groups of Sephadex with carboxymethyl (CM) groups suppressed the complement-activating capacity of the polymer in a dose-dependent fashion so that Sephadex bearing an average of one or more CM groups per saccharidic unit exhibited no complement-activating ability. Blocking of CM groups on CM sephadex with amide bonds did not restore a complement-activating capacity to the polymer, indicating that intact hydroxyl groups of the sugar units are required for complement activation by Sephadex. CM Sephadex was also found to adsorb C3adesArg which bound to the polymer with a calculated affinity of 1 × 10 6 1 × M −1. Substitution of Sephadex with carboxymethyl and benzylamide sulphonate groups which confers to the polymer the capacity to catalyse thrombin inactivation on its surface also suppressed the complement-activating capacity of Sephadex. Sephadex derivatives that lack complement-activating properties and adsorb anaphylatoxins may provide useful models for the design of cellulosic membranes and biomaterials with blood compatible properties.

Investigation of Bilirubin Removal by NK-110 Resin Hemoperfusion in Jaundiced Dogs

A jaundiced dog model was made by common bile duct-inferior vena cava shunt with a silicon rubber tube. Blood bilirubin levels increased from 0.25 +/- 0.16 (SD) mg% to 15 +/- 1.4 (SD) mg%. These dog models were treated with a column containing 200 gm of macroreticular resin NK-110 which was linked between the femoral artery and vein. The rate of blood flow through the column was 200 ml/min. It was shown that total bilirubin reduced from 15 +/- 1.4 (SD) to 7.4 +/- 0.61 (SD), conjugated bilirubin decreased from 6.97 +/- 0.63 to 3.5 +/- 0.33 (SD) and unconjugated bilirubin from 7.8 +/- 2.1 to 4.2 +/- 0.4 (SD). There were no significant changes in protein, electrolyte, blood gases and acid base balance. Results show that NK-110 resin has good blood-compatible and adsorption properties.

Etude de nouvelles membranes asymétriques à base de copolymère à blocs styrène‐isoprène‐styrène, 1. Synthèse, modification chimique et caractérisation

AbstractA styrene‐isoprene‐styrene block copolymer was selected for the preparation of new asymmetric membranes which have blood compatibility properties after chemical modification by addition of gazeous N‐chlorosulfonyl isocyanate to the double bonds of the polyisoprene sequences. The membranes were examined with a scanning electron microscope. The permeability of the membrane was studied as a function of time, pressure and viscosity.

A new asymmetric membrane having blood compatibility

A new asymmetric membrane has been synthesized from an ABA poly(styrene-bisoprene) (SIS) block copolymer ( M n = 89,000; 30 mol% polyisoprene with 68% 1,4 links and 32% 3,4 links). The asymmetric structure of the membrane obtained by casting the collodium (block copolymer in THF/DMF mixture) has been evidenced by scanning electron microscopy. A chemical modification of the membrane by reaction with gaseous chlorosulfonylisocyanate leads to a heparin-like compound with enhanced blood compatibility properties. Elemental analysis and infrared measurements show the presence of sulfamate and carboxylate groups on the modified block copolymer. These functional groups increase the hydrophilicity of the membrane and therefore enhance its water permeability.