Green Synthesis of Cissus Quadrangularis-loaded Titanium Dioxide Nanoparticles (CQ-TiO2) and Evaluation of its Antimicrobial, Antioxidant, Anti-inflammatory, and Biocompatibility activity in Human Periodontal Ligament Cells

Abstract Background: Periodontitis is characterized by microbial infection, oxidative stress, and chronic inflammation, resulting in damage to the periodontal tissues. Novel therapies incorporating plant-derived bioactive compounds loaded onto nanoparticles (NPs) represent promising strategies. Herein, we synthesize and biologically evaluate Cissus quadrangularis-loaded titanium dioxide (CQ-TiO 2 ) NPs for applications like periodontal disease management. Methods: CQ-TiO 2 NPs were synthesized using a green chemistry approach with CQ extract and evaluated for antimicrobial efficacy, which was determined by minimum inhibitory concentration (MIC) assays against Staphylococcus aureus and Streptococcus mutans ; antioxidant activity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay; anti-inflammatory potential was evaluated by quantitative Polymerase Chain Reaction (qPCR) analysis of pro-inflammatory cytokines (IL-2, IL-6, and TNF-α); osteogenic marker (TGF-β), and biocompatibility was investigated using the (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay) MTT assay on human periodontal ligament (PDL) cells. Results: Successful synthesis of Cissus quadrangularis-loaded TiO 2 nanoparticles (CQ-TiO 2 NPs) and scaffold fabrication exhibited potent antimicrobial activity, with low MIC values proving that the scaffold penetrates biofilm and inhibits adhesion. Strong antioxidant activity was confirmed through substantial DPPH radical inhibition. Gene expression analysis demonstrated significant downregulation of inflammatory cytokines IL-6, IL-8, and TNF-α and enhanced bone remodelling. Additionally, the MTT assay confirmed high biocompatibility and cell viability of human PDL cells exposed to CQ-TiO 2 NPs. Conclusion: The synthesized CQ-TiO 2 NPs exhibited remarkable antimicrobial, antioxidant, anti-inflammatory properties, and biocompatibility, underscoring their potential application as a novel therapeutic modality for effective periodontal regeneration.