The Antimicrobial Efficacy of Hypoxia Mimicking Cobalt Oxide Doped Phosphate-Based Glasses against Clinically Relevant Gram Positive, Gram Negative Bacteria and a Fungal Strain

Abstract

Bioactive phosphate glasses are of considerable interest for a range of soft and hard tissue engineering applications. The glasses are degradable and can release biologically important ions in a controlled manner. The glasses can also potentially be used as an antimicrobial delivery system. In the given study, novel cobalt-doped phosphate-based glasses, (P2O5)50(Na2O)20(CaO)30–x(CoO)x where 0 ≤ x (mol %) ≤ 10, were manufactured and characterized. As the cobalt oxide concentration increased, the rate of dissolution was observed to decrease. The antimicrobial potential of the glasses was studied using direct and indirect contact methods against both Escherichia coli (NCTC 10538) Staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 76615). The results showed strong, time dependent, and strain specific antimicrobial activity of the glasses against microorganisms when in direct contact. Antimicrobial activity (R) ≥ 2 was observed within 2 h against Escherichia coli, whereas a similar effect was achieved in 6 h against Staphylococcus aureus and Candida albicans. However, when in indirect contact, the dissolution products from the bioactive glasses failed to show an antimicrobial effect. Following direct exposure to the glasses for 7 days, osteoblast-like SAOS-2 cells showed a 5-fold increase in VEGF mRNA while THP-1 monocytic cells showed a 4-fold increase in VEGF mRNA expression when exposed to 10% CoO-doped glass compared with the cobalt free control glass. Endothelial cells stimulated with conditioned medium taken from cell cultures of THP-1 monocytes exposed to 10% CoO doped glass showed clear tubelike structure (blood vessel) formation after 4 h.