Interaction of blood components with heparin-immobilized polyurethanes prepared by plasma glow discharge

Abstract

The blood compatibility of poly(ethylene oxide) (PEO)-grafted and heparin (Hep) immobilized polyurethanes was investigated using in vitro plasma recalcification time (PRT), activated partial thromboplastin time (APTT), platelet adhesion and activation, and peripheral blood mononuclear cell (PBMC) adhesion and activation. In the experiment with plasma proteins, the PRT of the polyurethane (PU) surface was prolonged by PEO grafting and further prolonged by heparin immobilization. The APTT was prolonged on PU-Hep, suggesting the binding of immobilized heparin to antithrombin III. The percentage of platelet adhesion on PU was not much different from that on acrylic acid- and PEO-grafted PUs (PU-C, PU-6, PU-33), yet was substantially decreased by heparin immobilization (PU-6-Hep, PU-33-Hep). The release of serotonin from adhering platelets was slightly suppressed on PEO-grafted PUs yet significantly suppressed on heparin-immobilized PUs. In the PBMC experiments, the adhesion and activation of the cells were significantly suppressed on heparin-immobilized PUs, and the amount of interleukin-6 (IL-6) released from PBMCs stimulated with surface-modified PUs decreased with a decrease in PBMC adhesion.

The haemocompatibility of polyurethane–hyaluronic acid copolymers

“…controlled release of drugs), the anti-thrombogenicity of the PU-HA is built into its backbone; the HA possesses inherent bioactivity that it may impart to the material, which can allow for specific interactions with cells and other biomolecules. Because of the many favorable characteristics of PU for use in vascular applications, numerous groups have made anti-thrombotic modifications to PU materials [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], and the vast majority of these modifications have been performed via surface immobilization of heparin on the PU [16][17][18]21,26,27,30,32,33]. Heparin has been attached to PU via many different techniques, including via polyethylene glycol spacers in order to increase bioavailability of heparin and to simultaneously impart the material with both hydrophilicity and non-thrombogenicity [26].…”

“…Their significant mechanical mismatch with adjacent arterial tissue (o0.4 MPa tensile modulus of elasticity for native artery vs. 500 MPa for Teflon) leads to significant problems at the graft anastomoses such as thrombosis and hyperplasia induced by migration and growth of fibroblasts and smooth muscle cells. Another advantage of PUs is the relative ease of modifying their structures; surface and/or bulk modification of PU via attachment of biologically active species is possible due to reactive groups which are part of the PU structure, and such modifications may be designed to control or mediate host responses [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Finally, PUs may be fabricated via a myriad of processing technologies, including casting, electrostatic and wet spinning of fibers and monofilaments, extrusion, dip coating, or spraying [14].…”

“…As noted earlier, native GAGs such as heparin possess anticoagulant characteristics, and there have been numerous successful efforts to covalently modify PU surfaces with heparin in order to improve haemocompatibility [16][17][18]21,23,26,27,30,32,33]. While not as widely incorporated into vascular materials or devices as heparin, other native GAGs, such as hyaluronic acid (HA), similarly possess anti-thrombotic properties.…”

Surfaces having dual fibrinolytic and protein resistant properties by immobilization of lysine on polyurethane through a PEG spacer

“…Poly(ethylene oxide) (PEO, PEG) grafted surfaces have been shown to be highly effective in minimizing protein adsorption and platelet adhesion 8–17. Also immobilization of biomolecules through a PEG spacer is believed to stabilize the biomolecule and enhance its bioactivity18–21; various biomolecules including proteins and peptides can be covalently bound to the “distal” end of the tethered PEG chains 22–24…”

Immobilized heparin and its anti-coagulation effect on polysulfone membrane surface

“…To solve such problems, scientists and engineers have tried to immobilize heparin onto the dialysis membrane. [7,8,14] It is the objective to make a non-thrombogenic hemodialysis system, as well as to eliminate the risk of severe complications.…”