A biomimetic nanoplatform-reinforced hydrogel for multipronged STING suppression to remodel bone-immune homeostasis in diabetic periodontitis.

The innate immune disorder caused by diabetes significantly aggravates bone destruction in periodontitis. STING signaling is a critical target linking periodontal tissue damage and innate immune activation, yet related strategies remain scarce. In this study, we developed a biomimetic nanoplatform composed of a zinc-procyanidin coordination network that is encapsulated by an apoptotic neutrophil membrane and loaded with DNase I, and incorporated it into a reactive oxygen species (ROS)-responsive phenylboronic acid-modified poly(l-lysine) hydrogel system (NM-ZnPC@DNase/Gel). The loaded DNase I can efficiently clear neutrophil extracellular traps (NETs) and double-stranded DNA (dsDNA), thereby disrupting the NETs-dsDNA-STING signaling axis and inhibiting macrophage inflammatory activation. Meanwhile, the responsively released biomimetic nanoplatform can target and activate mitophagy in macrophages to inhibit mitochondrial damage and mitochondrial DNA (mtDNA) release under glucolipotoxicity, thus suppressing abnormal activation of the STING pathway and remodeling the bone-immune microenvironment. In addition, the system exhibited excellent injectable, self-healing, adhesive, antibacterial and hemostatic properties to match the clinical application scenarios of periodontitis. In vivo, this system effectively modulated the local inflammatory microenvironment and reversed alveolar bone resorption. In conclusion, we propose a novel therapeutic strategy to reverse immune dysregulation and tissue destruction in diabetic periodontitis through multipronged suppression of the STING signaling pathway.