In vitro cytocompatibility of antibacterial silver and copper-doped bioactive glasses

Fighting the formation of bacterial biofilm and simultaneously providing a bioactive environment for bone regeneration during the treatment of orthopedic infections is one of the greatest challenges in surgery. Moreover, the major global threat of rapidly increasing antimicrobial resistance calls for non-antibiotic alternatives. Bioactive glasses doped with antibacterial metal ions silver (Ag), or copper (Cu), offer a potential solution. However, an added challenge is the cytocompatibility of these antimicrobial biomaterials, which could be compromised due to the possible cytotoxic effect of the dopants. This work evaluates the cytocompatibility of two bioactive glasses, SBA2 and SBA3, either doped with Ag- (Ag-SBA2) or Cu-ions (Cu-SBA3) via ion-exchange process. The viability, proliferation, and morphology of human adipose stem cells (hASCs) were evaluated using different culture conditions: i) direct culture on glass discs, with and without pre-incubation, and ii) in medium containing glass dissolution byproducts. The release kinetics of the doped ions was evaluated in α-MEM and during cell culture. Moreover, the effect of protein adsorption on the cell response was studied by introducing a layer of fibronectin on the glass discs before direct culture with hASCs. Ag-SBA2 and Cu-SBA3 both initially inhibited the hASC viability in direct cell culture. However, cells remain viable with healthy morphology when cultured directly on pre-treated discs, or indirectly with the glass dissolution byproducts. This suggests that the cytotoxicity effect seems to arise from the contact toxicity between the cells and the material surface. Fibronectin adsorption significantly improved the cytocompatibility of Ag-SBA2, while Cu-SBA3 requires further optimization. To conclude, Ag-SBA2, through its contact toxicity, has the potential for treating early infection, without compromising long-term cytocompatibility and bioactivity. However, further optimization of the Cu-SBA3 glass is needed due to its cytotoxicity towards hASCs.