Shape-Depended Biological Properties of Ag3PO4 Microparticles: Evaluation of Antimicrobial Properties and Cytotoxicity in In Vitro Model-Safety Assessment of Potential Clinical Usage.

Implant-related infections are an emerging clinical and economic problem. Therefore, we decided to assess potential clinical usefulness and safety of silver orthophosphate microparticles (SOMPs) regarding their shape. We synthesized and then assessed antimicrobial properties and potential cytotoxicity of six shapes of SOMPs (tetrapod, cubes, spheres, tetrahedrons, branched, and rhombic dodecahedron). We found that SOMPs had a high antimicrobial effect; they were more efficient against fungi than bacteria. SOMPs exerted an antimicrobial effect in concentrations not toxic to mammalian cells: human fetal osteoblast (hFOB1.19), osteosarcoma (Saos-2), mouse preosteoblasts (MC3T3-E1), skin fibroblast (HDF), and mouse myoblast (C2C12). At higher concentration SOMPs, induced shape- and concentration-dependent cytotoxicity (according to MTT and BrdU assays). Tetrapod SOMPs had the smallest effect, whereas cubical SOMPs, the highest on cell viability. hFOB1.19 were the most resistant cells and C2C12, the most susceptible ones. We have proven that the induction of oxidative stress and inflammation is involved in the cytotoxic mechanism of SOMPs. After treatment with microparticles, we observed changes in levels of reactive oxygen species, first-line defense antioxidants-superoxide dismutase (SOD1, SOD3), and glutathione peroxidase (GPX4), metalloproteinase (MMP1, MMP3), and NF-κB protein. Neither cell cycle distribution nor ultrastructure was altered as determined by flow cytometry and transmission electron microscopy, respectively. In conclusion, silver orthophosphate may be a safe and effective antimicrobial agent on the implant surface. Spherical-shaped SOMPs are the most promising for biomedical application.