Periodontitis, characterized by microbial dysbiosis and immune dysregulation, destroys tooth-supporting tissues and negatively affects overall health. Current strategies face significant challenges in restoring damaged tissues while halting periodontitis progression. In this study, we introduce a live biotherapeutic product (LBP) in an engineered living hydrogel for comprehensive periodontitis therapy. A dental blue light-responsive hydrogel (LRG) was fabricated to deliver and confine live Lactobacillus rhamnosus GG (LGG) in periodontal pockets, endowing the LRG with sustained antibacterial and immunomodulatory effects. The LRG was engineered through peptide modification to also promote tissue regeneration. Both in vitro and in vivo evaluations confirmed the effectiveness of this integrated therapeutic strategy, which combines antibacterial, anti-inflammatory, and regenerative properties with an underlying immunomodulatory mechanism that involves suppressor of cytokine signaling (SOCS)3 upregulation and the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway suppression in macrophages. Demonstrating a new paradigm, this proof of concept highlights the synergistic integration of live organisms and synthetic material engineering in a chairside treatment to address the multifaceted etiology of periodontitis.
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