Nets Inhibition For Peri-Implantitis Via Microenvironment Modulation-Based Nanoparticles

This study aimed to validate the efficacy of a novel nano-based drug delivery system in targeting suppression of neutrophil extracellular traps (NETs) release with an organ-on-chip model of peri-implant soft tissue, and to elucidate its key roles and molecular mechanisms in regulating the immune microenvironment of peri-implantitis. We developed a novel organ-on-a-chip to model peri-implant soft tissue inflammation, studying NETs' effects on neutrophils, macrophages, and fibroblasts' inflammatory transformation. NAMO@Cur@AIE nanoparticles (loaded with CXCR2 antagonist and curcumin) were prepared for photothermal therapy. Therapeutic efficacy was assessed via NETs formation, ROS levels, and cytokines (IL-1β, TNF-α). Chip tissues underwent HE staining, IHC, and RNA-seq. The results showed that the organ-on-a-chip model we developed well replicated the structural and functional characteristics of the soft tissue surrounding the implant. Co-localization of membrane receptors with NAMO@Cur@AIE NPs was successfully detected on the surface of neutrophils. The application of nanoparticles significantly reduced the generation of NETs (p = 0.007), IL-1β (p < 0.001) and TNF-α (p < 0.05) secreted by macrophages and fibroblasts, and M1 polarization of macrophages. Moreover, the ROS clearance rate reached 66.30%. The model we constructed mimics the structure and function of peri-implant. NAMO@Cur@AIE NPs show a good ability to inhibit NETs, which provides a new strategy for the treatment of peri-implantitis.