Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2017)

Magnesium oxide (MgO) is a bioactive ceramic of increasing interest for bone applications. However, as MgO is relatively new to medical applications, there are limited publications on the cytocompatibility and bioactivity of MgO. In this work, we explore the properties of MgO nanoparticles (nMgO) in both bare form and as a component of polymeric composites.

Bare nMgO was reactive in simulated physiological environments, creating concentration-dependent effects. Specifically, nMgO has dynamic effect on bone marrow derived mesenchymal stem cells (BMSCs) and cell culture medium, Dulbecco’s Modified Eagle Medium (DMEM) with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (P/S). At low concentrations, nMgO enhanced the proliferation of BMSCs, but in concentrations exceeding 500 µg/mL there was significant cell death. However, increasing nMgO caused decrease in Ca2+ in DMEM, indicating that nMgO may enhance deposition of calcium salts. Much of this activity may be attributed to the dissociation of nMgO which resulted in release of Mg2+ and OH-. MgO nanoparticles readily dissociated in DMEM and simulated body fluid (SBF) due to pH and biological buffering effects. Developing polymeric nanocomposites with nMgO provided a way to mitigate dissociation of nMgO while maintaining beneficial effects to cells.

Several nMgO nanocomposites were evaluated. First, a method to increase dispersion of nMgO in poly (lactic-co-glycolic acid) (PLGA) using purely mechanical stimulation was developed. These composites were compared with composites of nanophase hydroxyapatite (nHA) in PLGA. Hydroxyapatite is a naturally occurring calcium phosphate, well-established for bone applications. Optical transparency measurements confirmed increased dispersion. However, the release of nMgO from nMgO/PLGA was found to exceed tolerable levels for BMSCs. Less nMgO was utilized in subsequent studies but to maintain the mechanical support from nanoparticle filling in PLGA, triphasic composites of PLGA/HA/MgO were developed. Improved cell response was observed when the amount of nMgO was decreased to 1-5 wt% compared to composites with 30 wt% nMgO, but we did not observe improved cell response when compared to PLGA/HA composites with 30 wt% nHA. However, these solvent-casted nanocomposites served as a guideline for the development of a thermogelling hydrogel containing nHA and nMgO.

PLGA-PEG-PLGA (PLGA block linkage with PEG, PbP) was utilized for its thermogelling properties. The presence of nMgO initially helped to stabilize the hydrogel. However, this property was lost as nMgO hydrated and eventually dissociated leading to loss of structural integrity of the hydrogel. As such, nMgO can be a useful additive to materials for bone regeneration but its reactivity means that it should be coated to preserve its beneficial properties and mitigate dissociation.

    Cover page: Magnesium Oxide Based Nanocomposites for Bone Repair
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2018)
    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.
      Cover page: Antimicrobial Activities and Mechanisms of Magnesium Oxide Nanoparticles (nMgO) against Pathogenic Bacteria, Yeasts, and BiofilmsCreative Commons 'BY' version 4.0 license
      Top