Identification of mesenchymal stromal cell survival responses to antimicrobial silver ion concentrations released from orthopaedic implants

Abstract

Antimicrobial silver (Ag+) coatings on orthopaedic implants may reduce infection rates, but should not be to the detriment of regenerative cell populations, primarily mesenchymal stem/stromal cells (MSCs). We determined intramedullary silver release profiles in vivo, which were used to test relevant Ag+ concentrations on MSC function in vitro. We measured a rapid elution of Ag+ from intramedullary pins in a rat femoral implantation model, delivering a maximum potential concentration of 7.8 µM, which was below toxic levels determined for MSCs in vitro (EC50, 33 µM). Additionally, we present in vitro data of the reduced colonisation of implants by Staphylococcus aureus. MSCs exposed to Ag+ 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 µM Ag+, suggesting that a subpopulation of clonal MSCs was sensitive to Ag+ exposure. At a molecular level, surviving colony-forming MSCs treated with Ag+ 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 l-buthionine sulfoxamine eliminated MSC clonogenicity in the presence of Ag+, which was rescued by exogenous glutathione.

Shaping and Patterning Supramolecular Materials─Stem Cell-Compatible Dual-Network Hybrid Gels Loaded with Silver Nanoparticles

“…However, the gels incorporating a high Ag concentration (10.0 mM AgNO 3 ) showed a rather large empty area around them (2.90–3.60 mm; Figure S41), indicating the toxicity of these materials to stem cells. This is in line with previous studies showing that high concentrations of Ag + ions can affect mesenchymal stem cell survival and function in vitro and in vivo. , …”

“…This is in line with previous studies showing that high concentrations of Ag + ions can affect mesenchymal stem cell survival and function in vitro and in vivo. 73 , 74 …”

“…This is in line with previous studies showing that high concentrations of Ag + ions can affect mesenchymal stem cell survival and function in vitro and in vivo. 73,74 To obtain further preliminary data on biocompatibility and explore a range of nontoxic AgNP concentrations, we performed an Alamar Blue assay on Y201 cells grown on gels with different AgNP loadings and control gels without AgNPs.…”

Electric Spark Deposition of Antibacterial Silver Coating on Microstructured Titanium Surfaces with a Novel Flexible Brush Electrode

“…The release of silver ions appears to be time-dependent. A sharp increase in silver ion concentration was observed within the first four days, and then, its release slowed down, and a plateau was reached in 2 weeks with a cumulative concentration of 3.85 μg/L, a concentration level that is capable of rendering an antimicrobial efficacy and is below cytotoxic levels (3564 μg/L) . There are many studies showing that silver ions release can be related to many factors, such as the responsive release of pH and GSH .…”

Titanium-Tantalum Alloy Surface Modification by Hydroxyapatite Layer on TiO2 Nanotubes: Effect on Microbial Activity

“…The biofilm of bacteria comprises microorganisms in which cells stick to each other and also to a surface 10 . In this context, non-traditional antimicrobial agents have been identified as hopeful tools against resistant bacteria to traditional antibiotic *e-mail: pat_capellato@yahoo.com.br drugs 11 . One kind of non-traditional antimicrobials newly introduced is nanomaterials.…”