Interactions between whole blood and TiO₂ surfaces with focus on adhesion and activation of PMN granulocytes

Sammanfattning: Foreign materials come in contact with the human body more and more frequently. The surgical procedure of inserting an implant into the body will cause bleeding, evoke an inflammatory response and initiate a healing process, ultimately leading to acceptance or rejection of the material. The implant will first encounter blood, and the importance of this first contact on the future fate of the material is largely unknown. Titanium is a biomaterial used in bone-anchored implants. It is known for its high biocompatibility, but the reason for the successful use of this material is only partly known. The oxide covering titanium is thought to be one factor influencing the biological response. The topography and wettability of the material are other influential factors.In this thesis the contact between whole blood and modified titanium surfaces was studied. The titanium surfaces differed with respect to surface roughness, wettability, and thickness of the surface oxide. The adsorption of plasma proteins and the adhesion and activation of platelets and leukocytes were investigated with focus on PMN granulocyte function.The results showed that a sequence of events take place on a titanium surface in contact with blood. Adsorption of proteins was detected after 5 seconds. After 5 seconds platelets had adhered to the surface and were activated after 4-8 minutes. It took approximately 8 minutes before PMN granulocytes adhered to the surface and about 30 minutes before they were in a primed state. Activation of platelets and priming of PMN granulocytes were more influenced by changes in surface roughness of titanium than of changes in oxide thickness. The cells were more activated/primed on rough surfaces than on smooth surfaces. The response of PMN granulocytes to hydrophilic and hydrophobic TiO2 surfaces showed differences in both adhesion mechanism and receptor expression during the first hour of contact between metal and blood. On hydrophilic titanium the cells adhered in a FcgIII receptor dependent manner and underwent transient priming on the surface. On hydrophobic titanium a platelet mediated adhesion via PSGL-1 was implicated and the priming was not transient. Contact with the titanium surfaces did not induce a respiratory burst from the PMN granulocytes and did not impair their ability to mount a respiratory burst upon stimulation.In conclusion, this thesis shows that the PMN granulocyte response to titanium is sensitive to changes in both surface structure and wettability.