Abstract
            Background. Polylactic-co-glycolic acid and zinc oxide (PLGA-ZnO) nanocomposite has been  investigated for its antibacterial properties, which could be beneficial for adding to wound  dressings after periodontal surgery. However, its cytotoxicity against human gingival fibroblasts  (HGFs) remains unclear and should be evaluated.  
  Methods. ZnO nanoparticles were synthesized using the hydrothermal method. These metallic  nanoparticles were incorporated into the PLGA matrix by the solvent/non-solvent process.  The nanomaterial was evaluated by field emission scanning electron microscopy (FESEM),  Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), and x-ray diffraction (XRD)  analyses. HGF cells were acquired from the National Cell Bank and categorized into four  groups: ZnO, PLGA, ZnO-PLGA, and control. The cells were exposed to different ZnO (1, 20,  40, 60, 80, and 100 µg/mL) and PLGA (0.2, 4, 8, 12, 16, and 20 µg/mL) concentrations for 24  and 48 hours. The cytotoxicity was tested using the MTT assay. The data were analyzed using  SPSS 25, and P<0.05 was considered statistically significant.  
  Results. ZnO nanoparticles exhibited significant toxicity at≥40 µg/mL concentrations after 24  hours. Cell viability decreased significantly at all the tested concentrations after 48 hours of  exposure. PLGA-ZnO cell viability in 24 hours was similar to the control group for all the  concentrations up to 80 µg/mL.  
  Conclusion. ZnO nanoparticles could be toxic against HGF in high concentrations and with  prolonged exposure. Therefore, incorporating ZnO nanoparticles into a biocompatible polymer  such as PLGA could be a beneficial strategy for reducing their toxicity.