Modulating Neutrophil Extracellular Trap Formation In Vivo with Locoregional Precision using Differently Charged Self-Assembled Hydrogels

Abstract

Neutrophil extracellular traps (NETs) are DNA networks released by neutrophils first described as a defense response against pathogens but have since been associated with numerous inflammatory diseases. The ability to induce NETs with locoregional specificity in vivo could facilitate studying this response in the context of disease and therapy with unprecedented control. We report the unexpected discovery that hydrogel charge predictably modulates the formation of NETs. Positively charged gels induce rapid NET release whereas negatively charged gels do not. This differential immune response to our self-assembled peptide gels enabled the development of a material platform that allows rheostat-like modulation over the degree of NET formation with anatomical and locoregional control.