Abstract
Bioactive glasses have been developed for medical applications in the body for bone and tissue repair and regeneration. We have developed a borate-containing bioactive glass (13-93B3, referred to as B3), which is undergoing clinical trials to assess its wound-healing properties. To complement the healing properties of B3, metal ion dopants have been added to enhance its antimicrobial properties. Bioactive glasses doped with silver, gallium or iodine ions were found to have broad spectrum antimicrobial effects on clinically relevant bacteria including MRSA. While the B3 glass alone was sufficient to produce antibacterial effects on select bacteria, adding dopants enhanced the broad-spectrum antibacterial properties: Live-Dead staining fluorescence microscopy suggests cell membrane integrity is disrupted in gram positive bacteria exposed to the glass compounds, but not gram negative bacteria, indicating multiple mechanisms of action for each glass formulation.
Highlights
Hospital-acquired infection, known as nosocomial infection, is a major health care problem that results in longer hospital stays, an increase in the cost of healthcare, and health risks in patients
Bioactive glasses doped with silver, gallium or iodine ions were found to have broad spectrum antimicrobial effects on clinically relevant bacteria including methicillin resistant S. aureus (MRSA)
While the B3 glass alone was sufficient to produce antibacterial effects on select bacteria, adding dopants enhanced the broad-spectrum antibacterial properties: Live-Dead staining fluorescence microscopy suggests cell membrane integrity is disrupted in gram positive bacteria exposed to the glass compounds, but not gram negative bacteria, indicating multiple mechanisms of action for each glass formulation
Summary
Hospital-acquired infection, known as nosocomial infection, is a major health care problem that results in longer hospital stays, an increase in the cost of healthcare, and health risks in patients. Since silver-doped silicate bioactive glasses are well-studied, there are various proposed mechanisms for how silver inhibits bacterial growth and gives bioactive glass bactericidal capabilities Such proposed mechanisms include complexing with thiol [1], sulfydryl, amino, or hydroxyl functional groups [13], competing with copper ions as a cofactor in transport or enzymatic reactions [13], general toxicity [13] [22], disruption of aliphatic carbon-hydrogen bonds by insertion of carbenes [23], DNA damage by arene-purine hydrophobic interactions [23], direct binding to DNA [1], increased permeability and disruption of cell membranes [1], and inhibition of respiratory [1] or signaling [21] enzymes. Further studies have revealed that antimicrobial effects of gallium are likely intracellular and involve disruption of bacterial iron uptake [27] [28] From these findings, it is clear that the presence of borate as well as various ions, including gallium and iodine, may enhance the bactericidal activity of borate bioactive glasses. The mechanism of action by which the bioactive glasses worked against both gram-negative and gram-positive bacteria was further studied by Live-Dead fluorescence microscopy
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