Modulating Neutrophil Extracellular Trap Formation <i>In Vivo</i> with Locoregional Precision Using Differently Charged Self-Assembled Hydrogels

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. Diverse physical material properties have been shown to promote NET formation. Herein, we report the discovery that the charge of self-assembled peptide hydrogels predictably modulates the formation of NETs <i>in vivo</i> within the implanted material. 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.