Polydopamine Nanosheet‐Based Neutrophil Extracellular Trap Scavengers Inhibit Periodontal Bone Loss by Modulating Neutrophil‐Macrophage Interactions

ABSTRACT Abnormal neutrophil‐macrophage communications induced by excessive inflammatory mediators may be crucial in periodontal inflammatory bone resorption. However, regulating the behavior of multiple immune cells without normal functions compromission remains a challenge. Here, an inflammatory mediators‐scavenging polydopamine (PDA) nanosheet, termed APDA‐PEI, was prepared through the template directed self‐assembly and surface chemistry‐based graft of polyethyleneimine. Neutrophil extracellular traps (NETs), key activators of macrophage inflammatory signaling, are captured through the synergistic interactions between APDA‐PEI nanosheets and the DNA backbones, including π – π stacking and electrostatic adsorption. Reactive oxygen species, a stimulation for neutrophil hyperactivation, was neutralized based on the distinctive redox property of PDA. The duration of lesion retention was improved by incorporating of APDA‐PEI into gelatin‐methacrylic anhydride hydrogels (APDA‐PEI@GM). In vitro and in vivo studies demonstrated that APDA‐PEI@GM inhibits excessive release of neutrophil‐derived NETs and abnormal activation of Toll‐like receptor 9 signaling in macrophage, leading to a reduction in periodontal inflammatory bone resorption. This inflammatory mediators‐scavenging system provides new insights for precise structural engineering of nanomaterials design and inflammatory diseases therapy.