UC Riverside

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.