| dc.description.abstract | Biomaterials are used in the construction of medical devices intended to be in intimate contact with blood and tissues of the human body. For many of the biomaterials in direct contact with blood, the dominant mechanism leading to initiation of thrombus formation and inflammation, seems to be the adsorption of adhesive proteins onto the biomaterial surfaces. This adsorbed protein layer may determine the subsequent biological response to the surface, such as cell adhesion and activation of platelets and granulocytes. Blood exposed to polymer materials, commonly used in medical therapy, and to experimental model surfaces such as hydrophilic and hydrophobic quartz surfaces, with and without surface modifications by cellulose ethers was investigated in the present thesis. The kinetics and supramolecular structure of the adsorbed plasma protein layer, with special emphasis on fibrinogen, was measured by using ellipsometry, ELISA, fluorescence- and electron microscopy. The subsequent biological response to this spontaneously adsorbed protein layer, such as cell adhesion and activation of platelets and granulocytes, was studied by using ELISA, fluorescence- and electron microscopy, flow cytometry and a new method developed to study the immediate inflammatory response of a blood-biomaterial interaction. In this model, the intracellular calcium level of test granulocytes in suspension reflects the presence of granulocyte activating factors, produced by the previous interactions between human blood and biomaterial. It was further attempted to evaluate granulocyte activation concerning complement activation, integrin expression, respiratory burst and priming. The results indicate that the wettability of the surfaces significantly affects the initial protein adsorption regarding its kinetics and supramolecular structure. A reduced adsorption of adhesive proteins was observed on the cellulose ether modified surfaces, and the results were in accordance with the findings of reduced cell adhesion and activation at these surfaces. Studies of the initial inflammatory response, show that blood exposition to hydrophilic and hydrophobic surfaces leads to the formation of humoral granulocyte activating factors, which differ between the surfaces. The present data also shows that biomaterials in clinical and laboratory use, differed in respect to the induction of an early inflammatory response during exposure of blood, and that this inflammatory response was dependent on the presence of anticoagulants used during the biomaterial exposure. In conclusion, the present thesis shows that the properties of a biomaterial surface and the choice of anticoagulants are important determinants of the outcome of the humoral and cellular response to a blood-biomaterial interaction. | en |
