Periodontitis, an inflammatory and infectious disease resulting from dental plaque, affects tooth-supporting tissues and interconnects with various systemic conditions. Advancing periodontal tissue regeneration stands as pivotal in periodontitis treatment. Presently, odontogenic stem cells garner substantial interest for dental pulp functional tissue regeneration. Essential to stem cell delivery success is the design of suitable drug delivery vehicles. Hence, this research introduces novel injectable antimicrobial peptide-grafted methacryloyl gelatin (GelMA-AMP) microspheres, housing hypoxia-inducible factor (HIF-1alpha), ensuring sustained release to stimulate osteogenic differentiation of deciduous dental pulp stem cells (SHEDs). Through in vitro co-culturing and preparation of HIF-1alpha@GelMA-AMP@SHED cell spheres, they were injected and transplanted into periodontal pockets for periodontitis treatment. Results display microsphere sizes averaging 93.92 +/- 6.00 mum, akin to human dental pulp, showcasing commendable cytocompatibility and in vitro antibacterial properties. Additionally, GelMA-AMP microspheres carrying HIF-1alpha enhance cell adhesion, proliferation, and extracellular matrix protein secretion. Notably, HIF-1alpha@GelMA-AMP@SHED microspheres were effective in reducing periodontal inflammation in vivo and promoting vascularization and tissue regeneration in the periodontal region. Consequently, the application potential of HIF-1alpha@GelMA-AMP@SHED hydrogel microspheres in periodontitis treatment appears promising.
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