Macrophage Membrane-Coated, Nanostructured Adsorbent Surfaces in a Microfluidic Device for Extracorporeal Blood Cleansing in Bacterially Induced Sepsis

Abstract

Sepsis is a dysregulated host response to infection that can lead to life-threatening organ failure. Circulating bacterial toxins, termed pathogen-associated molecular patterns (PAMPs), and excess cytokines produced by the immune system play a key role in the response that can progress into organ failure. Yet, no therapy is available to effectively remove these PAMPs and cytokines from the circulation or effectively block their action. Macrophage membrane coatings possess a natural blood compatibility, ideal for coating of adsorbent surfaces in extracorporeal blood-cleansing. Here, the ability of Escherichia coli-activated macrophage membrane coatings on silicon nanowired (SiNW) surfaces in a microfluidic device to remove PAMPs and cytokines from blood is determined. In vitro, such membrane-coated SiNW adsorbent surfaces remove significantly more PAMPS or cytokines from spiked human blood than achieved by hemofiltration. Cleansing of plasma from patients with bacterial sepsis using membrane-coated SiNW adsorbent surfaces reduces cytokine concentrations to healthy levels. In vivo, this coincides with two-fold better restoration of healthy cytokine levels after 4 h of extracorporeal blood-cleansing in rats with lipopolysaccharides (LPS)-induced sepsis and four-fold higher survival rates. Collectively, blood-cleansing microfluidic devices using bacterially activate macrophage membrane-coated SiNW surfaces are more effective than hemofiltration for therapeutic intervention in septic patients.