Injectable Theranostic Hydrogel For Periodontitis Treatment

To develop a multifunctional theranostic platform for precision periodontitis management. PEG-MoOx nanospheres were synthesized and characterized (SEM/TEM, EDS, XPS, XRD, ESR). Then Ce6 was loaded on (Ce6@PEG-MoOx), followed by validation of catalyzed oxygen production, photodynamic singlet oxygen generation (SOSG assay), and bactericidal efficacy against Escherichia coli, Staphylococcus aureus, Porphyromonas gingivalis, and Fusobacterium nucleatum. Besides, in vitro pro-angiogenic (HUVEC), anti-inflammatory (RAW264.7), and osteogenic (PDLSC) functions were assessed. Subsequently, Ce6@PEG-MoOx was incorporated in transglutaminase-crosslinked gelatin to construct an injectable hydrogel. Ligature-induced periodontitis models (Ethics Approval: SYSU-IACUC-2024-B0962, n=8) were established in 8-week-old male Sprague-Dawley rats to assess the in vivo efficacy of hydrogel for biofilm ablation, tissue regeneration promotion and photoacoustic imaging of periodontal pockets. Finally, Ref-RNA-seq, cell functional assays, and multiplex immunohistochemical examinations of sections were employed to elucidate the regeneration mechanism. Featuring mixed-valence Mo and abundant oxygen vacancies, PEG-MoOx endows the hydrogel with precise photoacoustic-based periodontal pocket monitoring and excellent catalytic activity which ameliorated the hypoxia microenvironment and enhanced Ce6-mediated biofilm eradication. Furthermore, the controlled releasing Mo promoted vascularization through PI3K/Akt pathway activation, alleviated inflammation, and stimulated osteogenesis, as validated both in vitro and in vivo. This injectable theranostic hydrogel established a novel approach for efficient periodontitis management, enabling quantitative visualization of periodontal pocket depth, biofilm eradication, and regeneration promotion. Concurrently, this study provides the first molecular evidence of the angiogenesis mechanism by Mo.