A photothermal therapy-based composite hydrogel for sequential management of inflammation control and bone regeneration in severe periodontitis

Chronic periodontitis remains a global issue in oral health and it is still a significant challenge to achieve the sequential management of inflammation control and bone repair. Herein, the antibiotic levofloxacin (LF) was loaded onto PDA-modified MXene (PDMM) 2D-composite nanosheets and embedded into the injectable hydrogel matrix of hyaluronic acid methacrylate (HAMA) to construct a 2D-nanomaterial composite hydrogel treatment platform (PDMM@LF-HAMA), which can initially control inflammation through antibacterial effects, alleviate diffuse gingival bleeding and then promote bone regeneration with further photothermal therapy. The composite hydrogel exhibited mild photothermal effects under near infrared (NIR) light and excellent photothermal conversion efficiency, which can promote cell proliferation and osteogenic differentiation <i>in vitro</i>. Finally, an <i>in vivo</i> experimental periodontitis model further demonstrated that the composite hydrogel achieved inflammation control within 2 weeks. Combined with NIR (808 nm, 0.4 W cm^-2), PDMM@LF-HAMA had a thicker periodontal epithelial fibrous layer and better alveolar bone height and morphology compared to the group without NIR after 8 weeks, while it also enhanced the expression levels of OCN and Runx2. Overall, this work provides an exploratory approach for the comprehensive management of periodontitis through the whole stage.