Synergistic Antimicrobial Metal Oxide-Doped Phosphate Glasses; a Potential Strategy to Reduce Antimicrobial Resistance and Host Cell Toxicity.

The emergence of antimicrobial resistant strains bacteria and a decline in the discovery of new antibiotics has led to the idea of combining various antimicrobials to treat resistant strains and/or polymicrobial infections. Metal oxide-doped glasses have been extensively investigated for their antimicrobial potential; however to date, most experiments have focused on single metal species in isolation. The present study investigates the antimicrobial potential of sodium calcium phosphates (P2O5)50(Na2O)20(CaO)30-X(MO)X, where M is cobalt, copper, or zinc as single species. In addition, this work studied the effect of co-doping glasses containing two different metal ions (Co + Cu, Co + Zn, and Cu + Zn). The antimicrobial efficacy of all glasses was tested against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterial strains, as well as a fungal strain (Candida albicans). Minimum inhibitory and bactericidal concentrations and time kill/synergy assays were used to assess the antimicrobial activity. An enhanced antimicrobial effect, at 5 mg/mL concentration, was exhibited by cobalt, copper, and zinc oxide glasses alone and in combinations. A synergistic antimicrobial effect was observed by Cu + Co and Cu + Zn against E. coli and Cu + Zn against S. aureus.

Evaluation of effectiveness of 45S5 bioglass doped with niobium for repairing critical-sized bone defect in in vitro and in vivo models.

Here, we investigated the biocompatibility of a bioactive sodium calcium silicate glass containing 2.6 mol% Nb2 O5 (denoted BGPN2.6) and compare the results with the archetypal 45S5 bioglass. The glass bioactivity was tested using a range of in vitro and in vivo experiments to assess its suitability for bone regeneration applications. in vitro studies consisted of assessing the cytocompatibility of the BGPN2.6 glass with bone-marrow-derived mesenchymal stem cells (BM-MSCs). Systemic biocompatibility was verified by means of the quantification of biochemical markers and histopathology of liver, kidneys, and muscles. The glass genotoxicity was assessed using the micronucleus test. The regeneration of a calvarial defect was assessed using both qualitative and quantitative analysis of three-dimensional microcomputed tomography images. The BGPN2.6 glass was not cytotoxic to BM-MSCs. It is systemically biocompatible causing no signs of damage to high metabolic and excretory organs such as the liver and kidneys. No mutagenic potential was observed in the micronucleus test. MicroCT images showed that BGPN2.6 was able to nearly fully regenerate a critical-sized calvarial defect and was far superior to standard 45S5 Bioglass. Defects filled with BGPN2.6 glass showed over 90% coverage compare to just 66% for 45S5 Bioglass. For one animal the defect was completely filled in 8 weeks. These results clearly show that Nb-containing bioactive glasses are a safe and effective biomaterial for bone replacement.