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We determined intramedullary silver release profiles in vivo, which were used to test relevant Ag<jats:sup>+<\/jats:sup> concentrations on MSC function in vitro. We measured a rapid elution of Ag<jats:sup>+<\/jats:sup> from intramedullary pins in a rat femoral implantation model, delivering a maximum potential concentration of 7.8\u00a0\u00b5M, which was below toxic levels determined for MSCs in vitro (EC<jats:sub>50<\/jats:sub>, 33\u00a0\u00b5M). Additionally, we present in vitro data of the reduced colonisation of implants by <jats:italic>Staphylococcus aureus<\/jats:italic>. MSCs exposed to Ag<jats:sup>+<\/jats:sup> prior to\/during osteogenic differentiation were not statistically affected. Notably, at clonal density, the colony-forming capacity of MSCs was significantly reduced in the presence of 10\u00a0\u00b5M Ag<jats:sup>+<\/jats:sup>, suggesting that a subpopulation of clonal MSCs was sensitive to Ag<jats:sup>+<\/jats:sup> exposure. At a molecular level, surviving colony-forming MSCs treated with Ag<jats:sup>+<\/jats:sup> demonstrated a significant upregulation of components of the peroxiredoxin\/thioredoxin pathway and processes involved in glutathione metabolism compared to untreated controls. Inhibition of glutathione synthesis using <jats:sc>l<\/jats:sc>-buthionine sulfoxamine eliminated MSC clonogenicity in the presence of Ag<jats:sup>+<\/jats:sup>, which was rescued by exogenous glutathione.<\/jats:p>","DOI":"10.1038\/s41598-020-76087-1","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T11:02:41Z","timestamp":1604401361000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of mesenchymal stromal cell survival responses to antimicrobial silver ion concentrations released from orthopaedic implants"],"prefix":"10.1038","volume":"10","author":[{"given":"Paul","family":"Souter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Vaughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Butcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Dowle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Dodd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Horner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Genever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"76087_CR1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.jcot.2015.04.004","volume":"6","author":"RV Thakore","year":"2015","unstructured":"Thakore, R. 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