Red Blood Cell-Induced Bacterial Margination Improves Microbial Hemoadsorption on Engineered Cell-Depleted Thrombi, Restoring Severe Bacteremia in Rats

Abstract

Extracorporeal hemoadsorption for treating bacteremia has exhibited limited success due to the lack of a clear strategy for effectively bringing bacterial cells into contact with the surface and universal bacteria-capturing substances. Here, a novel extracorporeal device is reported that can eliminate various intact bacteria from whole blood, employing microfluidic bacterial margination and engineered cell-depleted thrombus (CDT) presenting bacterial adhesin receptors. The critical strain rate of red blood cells (RBCs) (0.83 x 10-2) and the flow path height within about 300 mu m required for RBC axial migration in the flows are found. The subsequent RBC-bacteria collisions induced bacterial margination, facilitating their effective capture on the CDT surface on the channel wall. Fibrinogen and fibronectin in CDT are found to primarily contribute to capturing various bacteria. The extracorporeal CDT filters (eCDTF), which integrate all these principles, demonstrate significant depletion of major antibiotic-resistant and human fecal bacteria from the whole blood in vitro. Remarkable reductions in bacterial load and inflammatory markers in the rats lethally infected with methicillin-resistant Staphylococcus aureus are further confirmed, resulting in the restoration from bacteremia following extracorporeal treatment. The demonstration may propose a new design principle for hemoadsorption devices and elucidate the limited success of conventional treatments.