title: Different cytotoxicity responses to antimicrobial nanosilver coatings when comparing extract-based and direct-contact assays.
abstract: This study was performed to understand how the choice of cytotoxicity assay format affects the observed biocompatibility of nanosilver (nAg). nAg coatings are physical coatings containing silver (Ag) that have feature sizes of 100 nm or less, often in the form of nanoparticles or grains. They are used on medical devices to prevent infection, but in spite of this intended benefit, observations of potential cytotoxicity from nAg have been reported in numerous published studies. For medical device regulation, cytotoxicity testing is part of a biocompatibility evaluation, in which specific test methods are chosen based on the technological characteristics and intended use of a device. For this study, nAg-coated tissue culture polystyrene surfaces were prepared using magnetron sputter coating, resulting in nAg films of 0.2 to 311 µg cm(-2) Ag. These coatings exhibited nanometer-scale morphologies and demonstrated a > 4log10 reduction in Escherichia coli viability. It was observed that extracts of nAg caused no cytotoxicity to L929 mouse fibroblasts, but cells cultured directly on nAg coatings (direct-contact assay format) showed a dose-dependent reduction in viability by up to 100% (P < 0.001). Results using inductively coupled plasma mass spectrometry to measure Ag release suggested that extracts of nAg are not toxic because the dissolved Ag in those samples becomes less cytotoxic over time, probably owing to the reaction with cell culture media and serum (six-fold cytotoxicity reductions observed over a 24-h period). These findings highlight the potential value of direct-contact cytotoxicity testing for nAg in predicting biological interactions with cells or tissue in vivo.
authors: Division of Biology, Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD, 20993, USA.
authors: Eric M
authors: EM
authors: Sussman
authors: Brendan J
authors: BJ
authors: Casey
authors: Debargh
authors: D
authors: Dutta
authors: Benita J
authors: BJ
authors: Dair
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000009:adverse effects; D004926:Escherichia coli / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D018030:Silver Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D018675:Toxicity Tests / Q000379:methods
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D018030:Silver Compounds
keywords: antibacterial; biocompatibility; cytotoxicity; direct-contact; extract; medical device coating; nanosilver