Materials, Thromboresistant

Surfaces can be active in inducing blood clotting, and there is much current searching for thromboresistant synthetic materials for use in surgical repair of blood vessels (see Ref. 111). It may be important that a protective protein film be strongly adsorbed [112]. The role of water structure in cell-wall interactions may be quite important as well [113]. 

Methods for preparing heparin-containing polymeric materials by means of ionic and covalent immobilization of heparin on various polymers are surveyed. The data on the biological activity of heparin are discussed as well as the probable mechanisms of thromboresistance enhancement endowed to polymeric materials by this anticoagulant. Some approaches toward an increased efficiency of anticoagulant properties of immobilized heparin are analyzed, and the position of heparin-containing polymers among other biomedical polymers is discussed. 

Of these the last one has been most widely used, since heparin-modified polymeric materials exhibit the highest and by today unsurpassed effects of thromboresistance enhancement. Many of these materials have not only proved to be potent in trials on animals, but have already found clinical application. These achievements have stimulated continuous interest in heparin-containing polymers (HCP) which is best manifested by listing the investigations performed in the field in recent years and still under way. They involve the new procedures for the synthesis of HCP providing minimal loss of activity of bound heparin, the studies of interactions of HCP with blood and its individual components, as well as on the mechanism of enhanced thromboresistance of HCP, and the search for new tasks for HCP. 

GBCH-polymers were the first synthetic materials that displayed relatively high thromboresistance. For instance, poly(methyl methacrylate) grafts, having been coated with GBCH and implanted in dog s vena cava, were patent for 14 days, while uncoated PMMA grafts were totally covered with thrombin within the first 2 hours44). 

The heparin content of the materials involving anion-exchange resins goes up to 800 ng/cm2, whereas the maximal heparin content of graphite-based polymers is 0.78 ng/cm2. All of the synthesized polymers, although exhibiting sufficiently high thromboresistance in in vitro tests (Table 3), drastically varied in their stability in various model media (Table 4). 

It seemed reasonable to anticipate that the synergism of these two features (high heparin content and stability of the resultant materials) would result in long-term thromboresistant polymers. The in vivo tests revealed, however, their extremely low thromboresistance as compared to the ionically bound heparin-containing polymers, in particular. The effect is assumed to be caused by a lack of sufficient mobility of the polymer-bound heparin molecules, which prevents the performance of the intrinsic anticoagulant properties of heparin. 

The prospects for this method as well as for the method involving the generation of free macroradicals by y-irradiation of heparin 95), are provided for by the variety of polymerizable monomers, which makes it possible to produce materials with various physico-mechanical and chemical properties. The in vitro thromboresistance of the copolymers obtained in this way was proportional to the heparin content (Table 9). 

The fact that thromboresistance of HCP is dependent on the method of immobilization of heparin, together with a rather low activity of covalently immobilized heparin, makes the idea of long-term enhancement of thromboresistance of polymers on their heparinization doubtful 54,70,71J. Naturally, the answer can be given only after a detailed analysis of the interaction of HCP with blood and its components and clarification of the mechanism of the effect of the immobilized heparin on the blood clotting system and relying on the results of in vivo tests of these materials are necessary. 

Mechanism of Enhanced Thromboresistance of Polymeric Materials in the Presence of Heparin... 

Jordan SW, Chaikof EL. Novel thromboresistant materials. J. Vase. Surg. 2007 45 A104-115. 

Other concerns regarding the practicality of surface bound heparin for the preparation of materials with long-term thromboresistance remain. Because the interaction of heparin with platelets is unclear (31), whether the immobilized heparin causes greater thrombosis under conditions where platelet deposition is more important than fibrin formation remains to be shown. The passivating effect of antithrombin III on platelet consumption caused by surface-bound heparin is a significant observation in this context (32, 33). 

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