Abstract:
Introduction: The need for synthetic materials has constantly increased in many parts of medicine, in the field of heart surgery biomaterials are especially needed for the extracorporeal circulation. However, the contact of the blood with these artificial surfaces is not unproblematic since pathophysiologic reactions of the organism are induced. The hemocompatibility of polymeric materials has already been improved by different surface modifications over the last years. In this context an important role is attributed to the selective adsorption and activation reactions of plasma proteins to the artificial surfaces. In this paper six different tube materials were compared by measuring their binding capacities of different plasma proteins and their activation of soluble markers in the blood relating to their hemocompatibility.
Methods: Heparinized whole blood from healthy donors was filled into the different tubings of 50 cm length which were closed into circuits, these tubing loops were then rotated vertically. After 0 min, 60 min and 120 minutes of blood recirculation the soluble activation markers (thrombin-antithrombin III-complex, b-thromboglobulin, terminal-complement-complex, PMN-elastase) were measured by ELISA kits. Parallelly, the adsorption intensities of the plasma proteins were measured: After 15 min, 60 min and 120 min of recirculation the tubes were rinsed extensively, cut into pieces of 2 cm length and fixed. On the inner surface of these tube pieces the adsorbed plasma proteins were analysed in a semiquantitative way by a direct ELISA technique. Further, the tubes were rinsed after 120 minutes of recirculation and the adsorbed proteins were eluted, separated by SDS-PAGE and detected in the immunoblot by the different antibodies (C1-esterase-inhibitor, antithrombin III, high-molecular-weight kininogen, albumin, fibronectin, complement factor C3, heat-shock protein 70, platelet receptor CD41, fibrinogen).
Results: 2 materials showed, compared to the other 4 materials, a considerably better biocompatibility which could be shown, among other results, by the lower concentrations of b-TG and TCC. Further, these two coatings showed the highest binding capacities for AT-III, C1-esterase-inhibitor and HMWK. In contrast, the affinity of these surfaces to fibrinogen, fibronectin, C3 and CD41 was low. Materials with a comparatively worse hemocompatibility adsorbed only little C1-esterase-inhibitor, AT-III and HMWK, but increased fibrinogen, C3, fibronectin and CD41.
Discussion: In this study it could be shown that very different surfaces can have a very similar protein adsorption pattern. Interestingly, these results correlated with a comparable hemocompatibility of the corresponding materials. These findings support the hypothesis that the selective adsorption of certain plasma proteins to artificial surfaces can directly represent the extent of their hemocompatibility. These data can help evaluating current biomaterials in terms of their hemocompatibility on the one hand. On the other hand these results can be used for the development of new biomaterials. The identified plasma proteins might for example be immobilised on surfaces and their effects on an improved biocompatibility could be evaluated.