Surface modification of polyetherimide/polyvinylpyrrolidone membranes via covalent grafting of heparin: in vitro evaluation of hemocompatibility

Abstract

Heparin is a well-known substance commonly introduced in the bloodstream in many medical procedures to avoid thrombogenicity. Polymer membranes used for biomedical applications, such as in hemodialysis and blood oxygenators, must also have good antithrombogenic and biocompatibility characteristics. Recently developed polyetherimide/polyvinylpyrrolidone (PEI/PVP) hollow fiber membranes showed good potential as an alternative to clinically available membranes, as evaluated by the transport properties of blood-targeted molecules relevant in the treatment of patients with renal chronic diseases. Aiming at improving the hemocompatibility of these membranes, the incorporation of heparin onto their surface was sought as a promising attempt to achieve this goal. In this work, flat sheet PEI/ PVP membranes were prepared by the phase inversion technique and were functionalized through the covalent grafting of heparin. Characterization included the follow-up of hydrophilicity, protein adsorption, prothrombin time (PT), activated partial thromboplastin time (aPTT), hemolysis occurrence, platelet adhesion, and complement system activation. The results showed that heparinization resulted in more hydrophilic membranes (contact angle reduced from 76.5° to 58.5°) and in the reduction of protein adsorption by more than 50%. In contact with human blood, these membranes reduced the occurrence of platelet adhesion, increased aPTT from 34 to 46 s, and did not lead to complement system activation. Such PEI/PVP membranes have therefore remarkable antithrombogenic and biocompatibility characteristics, which are highly desired for use in biomedical applications such as hemodialysis filters.