IF 26.8! A dual-action nucleoside supramolecular hydrogel combats periodontitis by disrupting the bacteria-osteoclast cascade reaction

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Periodontitis is a highly common inflammatory oral disease and a recognized risk factor for various systemic diseases. The main therapeutic challenge of periodontitis lies in addressing alveolar bone loss caused by the complex interactions of microbial dysbiosis, immune imbalance, and bone homeostasis disruption. We identified a positive feedback loop between periodontal bacteria and osteoclast (OC)-mediated bone resorption and designed a novel self-drug delivery system (APC hydrogel) aimed at breaking this destructive cycle.This supramolecular hydrogel is composed of PEGylated, structurally optimized nucleoside derivatives, self-assembled through multivalent hydrogen bonds, and exhibits good biocompatibility and metabolic stability in vivo. Functionally, the hydrogel exerts a dual effect by sequentially eliminating key periodontal pathogens and inhibiting OC activity. In a ligature-induced periodontitis model, local application of the hydrogel restored microbial homeostasis and reduced alveolar bone loss by approximately 60%.Mechanistic studies show that APC metabolites activate the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway in OC precursors, thereby preventing their differentiation into mature bone-resorbing cells. This dual-action approach effectively disrupts the pathogenic cascade of microbial infection and osteoclastic bone destruction, redefining localized treatment strategies for periodontitis on a single platform and highlighting the broader potential of nucleotide-based supramolecular systems in treating inflammation-related bone loss.

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Pub Date : 2025-12-24

DOI: 10.1002/adma.202516181

Qingxuan Wang,  Yuxi Zhao,  Lingshuang Han,  Changfu Li,  Zheng Wang,  Xiaoqi Zhang,  Tiannan Liu,  Kaichao Wang,  Xianglong Han,  Liang Xie,  Wenli Lai,  Hang Zhao