Blood coagulation on biomaterials requires the combination of distinct activation processes

The rational design of hemocompatible materials requires a mechanistic understanding of activation processes induced at the blood-material interface. Binary self-assembled monolayers of alkyl thiols (SAMs) with various ratios of -CH3 and -COOH terminations were used to study the relevance of hydrophobic and negatively charged surfaces for the initiation of blood coagulation. Platelet adhesion and activation of the intrinsic coagulation pathway scaled with the surface composition: the numbers of adherent platelets were highest on the 100%-CH3 surface whereas the greatest contact activation was seen on 100%-COOH surfaces. In vitro whole blood incubation assays showed, however, that the surfaces exposing either -CH3 or -COOH groups induced comparably low levels of thrombin formation while the surfaces with intermediate contents of both terminating groups had significantly higher values. These results reveal that contact activation and platelet adhesion have a strong synergistic effect on coagulation on blood-contacting materials even though these events in isolation are not sufficient to induce substantial thrombin formation. Successful surface design strategies for hemocompatible materials therefore need to carefully consider the interplay of both processes.