AUTHOR=Pimentel Bruna Natália Alves da Silva , De Annunzio Sarah Raquel , Assis Marcelo , Barbugli Paula Aboud , Longo Elson , Vergani Carlos Eduardo 

TITLE=Biocompatibility and inflammatory response of silver tungstate, silver molybdate, and silver vanadate microcrystals

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1215438

DOI=10.3389/fbioe.2023.1215438

ISSN=2296-4185

ABSTRACT=<p>Silver tungstate (α-Ag<sub>2</sub>WO<sub>4</sub>), silver molybdate (β-Ag<sub>2</sub>MoO<sub>4</sub>), and silver vanadate (α-AgVO<sub>3</sub>) microcrystals have shown interesting antimicrobial properties. However, their biocompatibility is not yet fully understood. Cytotoxicity and the inflammatory response of silver-containing microcrystals were analyzed in THP-1 and THP-1 differentiated as macrophage-like cells, with the alamarBlue™ assay, flow cytometry, confocal microscopy, and ELISA. The present investigation also evaluated redox signaling and the production of cytokines (TNFα, IL-1β, IL-6, and IL-8) and matrix metalloproteinases (MMP-8 and -9). The results showed that α-AgVO<sub>3</sub> (3.9 μg/mL) did not affect cell viability (<italic>p</italic> &gt; 0.05). α-Ag<sub>2</sub>WO<sub>4</sub> (7.81 μg/mL), β-Ag<sub>2</sub>MoO<sub>4</sub> (15.62 μg/mL), and α-AgVO<sub>3</sub> (15.62 μg/mL) slightly decreased cell viability (<italic>p</italic> ≤ 0.003). All silver-containing microcrystals induced the production of O<sub>2</sub><sup>−</sup> and this effect was mitigated by Reactive Oxygen Species (ROS) scavenger and N-acetylcysteine (NAC). TNFα, IL-6 and IL-1β were not detected in THP-1 cells, while their production was either lower (<italic>p</italic> ≤ 0.0321) or similar to the control group (<italic>p</italic> ≥ 0.1048) for macrophage-like cells. The production of IL-8 by both cellular phenotypes was similar to the control group (<italic>p</italic> ≥ 0.3570). The release of MMP-8 was not detected in any condition in THP-1 cells. Although MMP-9 was released by THP-1 cells exposed to α-AgVO<sub>3</sub> (3.9 μg/mL), no significant difference was found with control (<italic>p</italic> = 0.7). Regarding macrophage-like cells, the release of MMP-8 and -9 decreased in the presence of all microcrystals (<italic>p</italic> ≤ 0.010). Overall, the present work shows a promising biocompatibility profile of, α-Ag<sub>2</sub>WO<sub>4</sub>, β-Ag<sub>2</sub>MoO<sub>4</sub>, and α-AgVO<sub>3</sub> microcrystals.</p>