Multifunctional thermosensitive hydrogel for synergistic antibacterial, anti-inflammatory and osteogenic effects to promote periodontal regeneration in periodontitis treatment

Abstract Periodontal disease therapy faces complex pathological challenges, including persistent anaerobic bacterial infection, excessive inflammatory activation and impaired alveolar bone regeneration. Monofunctional biomaterials thus fail to meet comprehensive clinical needs. Herein, we developed a multifunctional thermosensitive hydrogel delivery system. By encapsulating polydopamine-coated magnesium peroxide (MgO2@PDA) nanocomposites within a Pluronic F127-sodium alginate (F127-SA) matrix, the system achieves integrated synergistic therapy targeting the ‘antibacterial-anti-inflammatory-osteogenic’ axis. Systematic characterization demonstrated that the hydrogel exhibits rapid thermosensitive gelation and excellent shear-thinning properties. In vitro experiments confirmed that MgO2@PDA enables the sustained release of oxygen (O2) and magnesium ions (Mg2+), effectively inhibiting the proliferation of key periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum. Furthermore, the system downregulates the secretion of pro-inflammatory cytokines by macrophages stimulated with lipopolysaccharide (LPS). Notably, it significantly enhances osteoblast migration, differentiation and mineralization in vitro. In a rat periodontitis model, this hydrogel effectively attenuated local inflammatory responses, inhibited anaerobic pathogen proliferation and upregulated the expression of bone regeneration markers. In summary, this hydrogel integrates sustained drug delivery, microenvironment modulation and regenerative guidance functions, providing a novel strategy with clinical translation potential for the comprehensive treatment of periodontitis and periodontal tissue regeneration.