The development of silver - and copper-substituted melt-derived bioactive glasses with antimicrobial properties for the treatment of deep bone infections

Existing commercial bioactive glasses are reported to inhibit the growth of bacteria and are used to treat osteomyelitis. These formulations may be modified to introduce metal ions with even greater antimicrobial activity, but relatively little work has been reported, including the effects on osteoconductivity. This research aimed to investigate the substitution of CaO with Ag2O or CuO in the 45S5 and S53P4 compositions and determine the effects on properties, including their ability to inhibit the growth of pathogenic microorganisms. In the classical bioactive glass system SiO2-CaO-Na2O-P2O5, melt-derived glass was modified by molar substitutions of CaO with silver and copper and compared with those of its counterpart, 45S5 and S53P4. BG were characterised using various techniques, including (XRD) X-ray diffraction, X-ray fluorescence (XRF), and Differential Thermal Analysis (DTA). Glasses were then investigated for their ability to inhibit both planktonic and biofilm bacterial growth using clinically relevant bacteria (Staphylococcus aureus and Escherichia coli) and their biocompatibility on fibroblasts cells. Finally, the effect of Ag and Cu on BG bioactivity was investigated by immersion of the samples in simulated body fluid (SBF) Our results have shown that it was possible to produce glasses with Ag2O at the lowest concentration, with no significant changes to glass structure detected following silver substitution. It also was shown that the CuO was incorporated successfully in the glass system and has produced a homogenous glass frit. The incorporation of Ag2O and CuO conferred antimicrobial properties to the glass without apparently compromising its bioactivity. Ag and Cu BG exhibited a marked antimicrobial effect on S. aureus and E. coli at a concentration of 25 mg/mL. In comparison, 45S5 and S53P4 did not possess enhanced antimicrobial properties over the concentration range investigated. Our results show that Ag- and Cu- BG were found to strongly inhibit S. aureus biofilm formation, while both 45S5 and S53P4 did not exhibit similar behaviour. This improvement in antimicrobial activity was made without loss of in vitro biocompatibility; all BG showed similar levels of cell viability, and both Ag and Cu had no adverse effects on cultured fibroblast cell. Furthermore, there was no significant difference between tested samples after exposure to SBF, as surface reactivity was demonstrated in all modified bioactive glasses. It was concluded that Ag- and Cu-substituted bioactive glasses represent the first true multi-functional biomaterials with significant potential for use as antimicrobial bone graft substitutes to treat osteomyelitis and related bone infections.