Frontiers in molecular biosciences · 2026
Immune-modulating copper-doped bioactive glass-based injectable hydrogel for periodontitis therapy.
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Lv Huiqin, Ali Onaza, Tu Ting, Liu Zhe, Zhan Yunyan
Аннотация
BACKGROUND: Periodontitis, a chronic inflammatory disorder driven by microbial dysbiosis and aberrant host immune responses, poses a significant challenge to periodontal tissue regeneration owing to persistent infection and impaired osteogenesis.
OBJECTIVE: Herein, we engineered an injectable hydrogel (denoted Cu@BG-HA) via borate ester crosslinking of copper-doped mesoporous bioactive glass nanoparticles (Cu@BG, 480 nm) with hyaluronic acid, aiming to concurrently address antibacterial, immunomodulatory, and osteogenic deficits in the periodontal microenvironment.
METHODS: The Cu@BG-HA hydrogel was synthesized through dynamic borate ester bond formation between Cu@BG nanoparticles and HA polymer networks. The physicochemical properties, ion release kinetics, and therapeutic efficacy were systematically characterized using in vitro models of bacterial infection, macrophage polarization, and osteoblast differentiation.
RESULTS: The Cu@BG-HA hydrogel demonstrated sustained Cu2+ release over 24 days, achieving eradication rates of 99.8% ± 3.2% against Staphylococcus aureus and 98.6% ± 1.7% against Porphyromonas gingivalis. Under lipopolysaccharide/interferon-γ (LPS/IFN-γ) stimulation, the hydrogel effectively orchestrated macrophage phenotype switching from pro-inflammatory M1 toward anti-inflammatory M2 states in RAW264.7 cells. Furthermore, Cu@BG-HA markedly potentiated osteogenic differentiation of MC3T3-E1 pre-osteoblasts, evidenced by 1.8- and 1.7-fold enhancements in alkaline phosphatase activity and mineralized nodule formation, respectively, relative to control conditions.
CONCLUSION: Collectively, these findings establish Cu@BG-HA as a multifunctional, minimally invasive therapeutic platform that integrates potent antibacterial, immunomodulatory, and pro-osteogenic functionalities. This strategy offers substantial translational potential for periodontitis management and may be extendable to other inflammatory osteolytic pathologies.
OBJECTIVE: Herein, we engineered an injectable hydrogel (denoted Cu@BG-HA) via borate ester crosslinking of copper-doped mesoporous bioactive glass nanoparticles (Cu@BG, 480 nm) with hyaluronic acid, aiming to concurrently address antibacterial, immunomodulatory, and osteogenic deficits in the periodontal microenvironment.
METHODS: The Cu@BG-HA hydrogel was synthesized through dynamic borate ester bond formation between Cu@BG nanoparticles and HA polymer networks. The physicochemical properties, ion release kinetics, and therapeutic efficacy were systematically characterized using in vitro models of bacterial infection, macrophage polarization, and osteoblast differentiation.
RESULTS: The Cu@BG-HA hydrogel demonstrated sustained Cu2+ release over 24 days, achieving eradication rates of 99.8% ± 3.2% against Staphylococcus aureus and 98.6% ± 1.7% against Porphyromonas gingivalis. Under lipopolysaccharide/interferon-γ (LPS/IFN-γ) stimulation, the hydrogel effectively orchestrated macrophage phenotype switching from pro-inflammatory M1 toward anti-inflammatory M2 states in RAW264.7 cells. Furthermore, Cu@BG-HA markedly potentiated osteogenic differentiation of MC3T3-E1 pre-osteoblasts, evidenced by 1.8- and 1.7-fold enhancements in alkaline phosphatase activity and mineralized nodule formation, respectively, relative to control conditions.
CONCLUSION: Collectively, these findings establish Cu@BG-HA as a multifunctional, minimally invasive therapeutic platform that integrates potent antibacterial, immunomodulatory, and pro-osteogenic functionalities. This strategy offers substantial translational potential for periodontitis management and may be extendable to other inflammatory osteolytic pathologies.