Initiation of blood coagulation - Evaluating the relevance of specific surface functionalities using self assembled monolayers
Zusammenfassung der Projektergebnisse
Binary self assembled monolayers of functionally terminated alkyl thiols were successfully applied to demonstrate the relevance of material surface characteristics for initial processes of blood coagulation. The in vitro whole blood incubation of self assembled monolayers (SAM) enabled this research on the influence of surface wettability and charge on the hemocompatibility of biomaterials. This was achieved by a detailed description of protein adsorption, coagulation activation (contact activation + the impact of tissue factor) and cellular reactions (blood platelets and leukocytes). We studied the influence of surface properties on platelet- and contact activation, the two main actors of blood coagulation, which are often considered as separate mechanisms in biomaterials research. Results show a dependence of contact activation on acidic surface groups and a correlation of platelet adhesion to surface hydrophobicity. It was found that neither platelet adhesion - on hydrophobic surfaces - without concurrent contact activation, nor contact activation - on negatively charged surfaces - without the presence of activated platelets lead to strong thrombus formation. Clot formation resulting from the interplay of blood platelets and contact activation was only found on surfaces combining both surface groups but not on monolayers displaying extreme hydrophobic / acidic properties. These results evidence that surface design and testing of materials contacting blood needs to consider a complete picture of activation processes and the necessity to study biomaterial induced coagulation in the complex system of whole blood. Further on we addressed the relevance of surface properties for material related-induction of the Tissue Factor (TF) pathway. TF expression in leukocytes and leukocyte bound TF in whole blood after incubation with surfaces displaying –OH functionalities showed higher levels than on any CH3 and COOH exposing surfaces. In addition, a positive correlation between TF transcription and its presence on leukocytes, granulocyte activation and complement activation was found. However, the observed initiation of the extrinsic pathway did not trigger blood coagulation in the absence of tissue – a condition that is given in our whole blood incubation setup. The lack of correlation between leukocyte bound TF and coagulation activation is possibly a result of quick enzymatic TF inhibition. It can be concluded that TF does not activate blood coagulation in short term applications of biomaterials in blood contacting medical devices. Coagulation activation on surfaces with intermediate to longer blood contact may follow other mechanisms.
Projektbezogene Publikationen (Auswahl)
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Coagulation activation on SAM model surfaces with varied composition of hydrophobic and negatively charged alkanethiols. INEB - Instituto de Nacional Engenharia Biomédica. Porto, Portugal, 16.04.2008
Sperling C, Fischer M, Werner C
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Self assembled monolayers with varied hydrophobicity enable a mechanistic definition of blood coagulation activation. World biomaterials conference 2008; Amsterdam, Netherlands
Fischer M, Sperling C, Werner C
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Blood coagulation on biomaterials requires the combination of distinct activation processes. Biomaterials 2009;30:4447-56
Sperling C, Fischer M, Maitz MF, Werner C
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Interplay of platelets and contact activation boosts blood coagulation on biomaterials. European Conference of Biomaterials 2009; Lausanne, Schweiz
Fischer M, Sperling C, Maitz MF, Werner C
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Relevance of tissue factor for biomaterial associated blood coagulation. 53. Jahrestagung der Gesellschaft für Thrombose und Hämostaseforschung. Vienna, 04.02.2009 - 07.02.2009
Sperling C, Fischer M, Maitz MF, Werner C
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Synergistic effect of hydrophobic and anionic surface groups triggers blood coagulation in vitro. J Mater Sci Mater Med 2009;21:931-7
Fischer M, Sperling C, Werner C
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Interplay of platelets and contact activation boosts coagulation on biomaterials. 1. Joint Meeting GTH & NVTH, 54. Jahrestagung der Gesellschaft für Thrombose- und Hämostaseforschung. Nuremberg, 24.02.2010 - 27.02.2010
Sperling C, Fischer M, Maitz MF, Werner C
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The ability of surface characteristics of materials to trigger leukocyte tissue factor expression. Biomaterials 2010;31:2498-507
Fischer M, Sperling C, Tengvall P, Werner C
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Self assembled monolayers with varied hydrophobicity and charge enable a mechanistic definition of blood coagulation activation. Symposium Hemocompatibility of Biomaterials - State of the Knowledge and New Developments. Dresden, 08.09.2011 - 09.09.2011
Sperling C, Fischer M, Werner C
