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.

Angiogenic magnetic hydrogels are attractive for tissue engineering applications because their integrated properties can improve angiogenesis while providing magnetic guidance and stimulation for tissue healing. In this study, we synthesized magnetic nanoparticles (MNPs) with curcumin as an angiogenic agent, referred to as CMNPs, via a one-pot coprecipitation method. We dispersed CMNPs in hyaluronic acid (HyA) to create angiogenic magnetic hydrogels. CMNPs showed a slightly reduced average diameter compared to that of MNPs and a curcumin content of 11.91%. CMNPs exhibited a sustained slow release of curcumin when immersed in a revised simulated body fluid (rSBF). Both CMNPs and MNPs showed a dose-dependent cytocompatibility when cultured with bone marrow-derived mesenchymal stem cells (BMSCs) using the direct exposure culture method in vitro. The average BMSC density increased when the concentrations of CMNPs or MNPs increased from 100 to 500 μg/mL, but the cell density decreased when the nanoparticle concentration reached 1000 μg/mL. CMNPs showed a weaker magnetic response than MNPs both in air and in water immediately after synthesis but retained the magnetism better than MNPs when embedded in the HyA hydrogel because of less oxidation. CMNPs were able to respond to magnetic guidance even when the porcine skin or muscle tissues were placed in between the nanoparticles and external magnet. The magnetic hydrogels of HyA_CMNP and HyA_MNP promoted the adhesion of BMSCs in a direct exposure culture. The HyA_CMNP group also showed the highest secretion of the vascular endothelial growth factor with the release of curcumin in vitro. Overall, our magnetic hydrogels integrated the desirable properties of cytocompatibility and angiogenesis with magnetic guidance, thus proving to be promising for improving tissue regeneration.

Magnesium–zinc–calcium (Mg–Zn–Ca) alloys have attracted increasing attention for biomedical implant applications, especially for bone repair, because of their biocompatibility, biodegradability, and similar mechanical properties to human bone. The objectives of this study were to characterize Mg–2 wt % Zn–0.5 wt % Ca (named ZC21) alloy pins microstructurally and mechanically, and determine their degradation and interactions with host cells and pathogenic bacteria in vitro and in vivo in comparison with the previously studied Mg–4 wt % Zn–1 wt % strontium (named ZSr41) alloy and Mg control. Specifically, the in vitro degradation and cytocompatibility of ZC21 pins with bone marrow derived mesenchymal stem cells (BMSCs) were investigated using both direct culture and direct exposure culture methods. The adhesion density of BMSCs on ZC21 pins (i.e., direct contact) was significantly higher than on pure Mg pins in both in vitro culture methods; the cell adhesion density around ZC21 pins (i.e., indirect contact) was similar to the cell-only positive control in both in vitro culture methods. Interestingly, ZC21 showed a higher daily degradation rate, crack width and crack area ratio in the direct exposure culture than in the direct culture, suggesting different culture methods did affect its in vitro degradation behaviors. When cultured with Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA), ZC21 reduced bacterial adhesion on the surface more significantly than that of ZSr41 and Mg. The in vivo degradation and biocompatibility of the ZC21 pins for bone regeneration were studied in a mouse femoral defect model. The in vivo degradation rate of ZC21 pins was much slower than that of ZSr41 alloy and Mg control pins. After 12 weeks of implantation in vivo, the ZC21 group showed the shortest gap at the femoral defect, indicating that ZC21 pins promoted osteogenesis and bone healing more than ZSr41 and Mg control pins. Overall, the ZC21 alloy is promising for bone repair, while providing antibacterial activities, and should be further studied toward 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