Hemocompatibility evaluation of different silver nanoparticle concentrations employing a modified Chandler-loop in vitro assay on human blood.

Due to their antibacterial effects, the use of silver nanoparticles (AgNPs) in a great variety of medical applications like coatings of medical devices has increased markedly in the last few years. However, blood in contact with AgNPs may induce adverse effects, thereby altering hemostatic functions. The objective of this study was to investigate the hemocompatibility of AgNPs in whole blood. Human whole blood (n=6) was treated with different AgNPs concentrations (1, 3 and 30mgl(-1)) or with saline/blank solutions as controls before being circulated in an in vitro Chandler-loop model for 60min at 37°C. Before and after circulation, various hematologic markers were investigated. Based on the hematologic parameters measured, no profound changes were observed in the groups treated with AgNP concentrations of 1 or 3mgl(-1). AgNP concentrations of 30mgl(-1) induced hemolysis of erythrocytes and α-granule secretion in platelets, increased CD11b expression on granulocytes, increased coagulation markers thrombin-antithrombin-III complex, kallikrein-like and FXIIa-like activities as well as complementing cascade activation. Overall, we provide for the first time a comprehensive evaluation including all hematologic parameters required to reliably assess the hemocompatibility of AgNPs. We strongly recommend integrating these hemocompatibility tests to preclinical test procedures prior to in vivo application of new AgNP-based therapies.