Asiatic Acid-Loaded Hydrogel Ameliorates Diabetic Periodontitis via Mitophagy-Mediated M2 Macrophage Polarization

Emerging evidence highlights a bidirectional relationship between diabetes and periodontitis, with both conditions sharing common pathogenic mechanisms. Biomaterials capable of modulating macrophage polarization hold significant therapeutic potential for promoting tissue repair in diabetic periodontitis. Asiatic acid (AA), a clinically proven compound with potent antioxidant and antiinflammatory properties, presents an attractive therapeutic candidate. In this study, we developed a multifunctional hybrid hydrogel, AA@GO (AA@GO/SA/CCS, abbreviated as AA@GO), composed of sodium alginate (SA), carboxymethyl chitosan (CCS), and graphene oxide (GO) for effective AA delivery. The AA@GO hydrogel demonstrated remarkable mitophagy-enhancing capabilities, effectively reducing intracellular ROS levels and restoring mitochondrial function in macrophages. Notably, this material significantly increased the M2/M1 polarization ratio by facilitating macrophage phenotype switching from M1 to M2, thereby attenuating inflammatory responses. Our findings elucidate the unique mechanism of AA@GO hydrogel action and propose a promising novel strategy for diabetic periodontitis treatment through macrophage polarization regulation.