Magnesium oxide nanoparticle (nMgO) is a light metal based antimicrobial nanoparticle that can be metabolized and fully resorbed in the body. To take advantage of the antimicrobial properties of nMgO for medical use, it is necessary to determine the minimal inhibitory, bactericidal and fungicidal concentrations (MIC, MBC and MFC) of nMgO against prevalent infectious bacteria and yeasts. The objective of this study was to use consistent methods and conditions to reveal and directly compare the efficacy of nMgO against nine prevalent pathogenic microorganisms, including two gram-negative bacteria, three gram-positive bacteria with drug-resistant strains, and four yeasts with drug-resistant strains. The MIC of nMgO varied from 0.5 mg/mL to 1.2 mg/mL and the minimal lethal concentration (MLC) of nMgO at 90% killing varied from 0.7 mg/mL to 1.4 mg/mL against different pathogenic bacteria and yeasts. The most potent concentrations (MPC) of nMgO were 1.4 and/or 1.6 mg/mL, depending on the type of bacteria and yeasts tested. As the concentration of nMgO increased, the adhesion of bacteria and yeasts decreased. Moreover, S. epidermidis biofilm was disrupted at 1.6 mg/mL of nMgO. E. coli and some yeasts showed membrane damage after cultured with ≥0.5 mg/mL nMgO. Overall, nMgO killed both planktonic bacteria and disrupted nascent biofilms, suggesting new antimicrobial mechanisms of nMgO. Production of reactive oxygen species (ROS), Ca2+ ion concentrations, and quorum sensing likely contribute to the action mechanisms of nMgO against planktonic bacteria, but transient alkaline pH of 7 to 10 or increased Mg2+ ion concentrations from 1 to 50 mM showed no inhibitory or killing effects on bacteria such as S. epidermidis. Further studies are needed to determine if specific concentrations of nMgO at MIC, MLC or MPC level can be integrated into medical devices to evoke desired antimicrobial responses without harming host cells.

This article reports the quantitative relationship between the concentration of magnesium oxide (MgO) nanoparticles and its distinct biological activities towards mammalian cells and infectious bacteria for the first time. The effects of MgO nanoparticles on the viability of bone marrow derived mesenchymal stem cells (BMSCs) and infectious bacteria (both gram-negative Escherichia coli and gram-positive Staphylococcus epidermidis) showed a concentration-dependent behavior in vitro. The critical concentrations of MgO nanoparticles identified in this study provided valuable guidelines for biomaterial design toward potential clinical translation.

Magnesium oxide (MgO) and hydroxide [Mg(OH) 2 ] are conventionally considered insoluble in water and stable at high temperatures. However, in this study, we found significant dissociation of MgO and Mg(OH) 2 into ions when they were immersed in different physiologically relevant solutions in the form of 20nm and 10-nm nanoparticles respectively, under standard cell culture conditions in vitro, i.e., a 37°C, 5% CO 2 /95% air, sterile, humidified environment. The change in Mg 2+ ion concentrations and pH measured in the physiologically relevant solutions (e.g., Dulbecco's modified Eagle's Medium (DMEM), simulated body fluid (SBF), relevant chloride solutions, and deionized water) confirmed their dissociation. Possible mechanisms and contributing factors for dissociation of MgO and Mg(OH) 2 nanoparticles were discussed. The evidence suggests that nucleophilic substitution of OH − by Cl − in Mg(OH) 2 is energetically unfavorable and it is more likely that Cl − plays a role in the stabilization of intermediate forms of MgO and Mg(OH) 2 as it dissociates. The pH and buffering capability of the immersion solutions might have played the most significant role in dissociation of these nanoparticles when compared with the roles of chloride (Cl − ), proteins, and different buffering agents. This article provided the first evidence on the dissociation of MgO and Mg(OH) 2 nanoparticles in physiologically relevant conditions and elucidated possible factors contributing to the observed behaviors of these nanoparticles in vitro, which is important for their potential medical applications in vivo. Keywords Magnesium oxide (MgO) nanoparticles . Magnesium hydroxide [Mg(OH) 2 ] nanoparticles . Biofluids . Dulbecco's modified Eagle's Medium (DMEM) . Simulated body fluid (SBF) . HEPES buffer . Chloride (Cl − ) solutions

This article reports a new process for creating polymer-based nanocomposites with enhanced dispersion of ceramic nanoparticles without using any surfactants, and the resulted changes in their optical and biological properties. Specifically, dispersion of two different ceramic nanoparticles, that is, hydroxyapatite (nHA) and magnesium oxide (nMgO) nanoparticles, in a model biodegradable polymer, namely poly(lactic-co-glycolic acid) (PLGA), was studied. High-power sonication was integrated with dual asymmetric centrifugal (DAC) mixing to improve dispersion of nanoparticles during solvent casting. The polymer/solvent ratio was optimized to improve nanoparticle dispersion in the multistep processing, including enhancing the efficacy of sonication and DAC mixing and reducing nanoparticle sedimentation during solvent-casting. Microstructural characterization confirmed that this new process improved nanoparticle dispersion in nMgO/PLGA and nHA/PLGA nanocomposites. Improved nanoparticle dispersion increased the optical transparency visually and optical transmission quantitatively for both nHA/PLGA and nMgO/PLGA nanocomposites. Improved dispersion of nanoparticles improved the adhesion of bone marrow derived mesenchymal stem cells (BMSCs) on nHA/PLGA but decreased BMSC viability on nMgO/PLGA. This difference is likely because the chemistry of nHA and nMgO had different effects on BMSCs. This study provided a new process for enhancing dispersion of ceramic nanoparticles in a polymer matrix and revealed the effects of dispersion on optical properties and cell responses, which are valuable for engineering optimal ceramic/polymer nanocomposites for different biomedical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2692-2707, 2018.