Periodontitis is one of the major oral health issues worldwide, with significant impacts on oral health and patients's quality of life, but current therapies have not achieved optimal regeneration of periodontal tissue. This study developed scaffolds using natural tussah silk fibroin (TSF) cross-linked with regenerated silk fibroin (SF) nanofibers to improve mechanical properties and wet-state stability. Zinc oxide (ZnO) and polydopamine (PDA) composite nanoparticles were loaded into scaffold to impart its antibacterial and photothermal properties to construct a photo-responsive composite scaffold (ZnO/PDA/TSF-SF). After characterization, ZnO/PDA/TSF-SF demonstrated excellent antibacterial ability, biocompatibility, and photothermal stability. In vitro cell evaluations under 635 nm red light irradiation-mediated photo-biomodulation (PBM) demonstrated that ZnO/PDA/TSF-SF promoted fibroblast proliferation and enhanced expression of proteins and genes associated with tissue repair, such as collagen I (Col I), fibronectin (FN), and alpha smooth muscle actin (α-SMA). A rat model of periodontitis developed for evaluations of antibacterial and tissue repair effects showed that ZnO/PDA/TSF-SF improved alveolar bone and reversed bone loss. ZnO/PDA/TSF-SF improved inflammation significantly through reduction in tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 levels in serum and gingival tissues of modeled rats. Also, the scaffold markedly increased levels of anti-inflammatory cytokine interleukin-10 (IL-10) and elevated protein and mRNA expression levels of tissue repair-related proteins and endothelial cell markers. ZnO/PDA/TSF-SF scaffold exhibited good biocompatibility, osteogenesis, and photo-responsive antibacterial properties, thereby demonstrating therapeutic potential in treating periodontitis.
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