Three-Dimensional Hydrogel Constructs for Dosing Cells with Nanoparticles
Elisabeth Mansfield, Tammy L. Oreskovic, Nikki S. Rentz, Kavita M. Jeerage
In evaluating nanoparticle risks to human health, there is often a disconnect between results obtained from in vitro toxicology studies and in vivo activity, prompting the need for improved methods to rapidly assess the hazards of engineered nanomaterials. In vitro studies of nanoparticle toxicology often rely on high doses and short exposure times due to the difficulty of maintaining monolayer cell cultures over extended time periods as well as the difficulty of maintaining nanoparticle dispersions within the culture environment. In this work, tissue engineered constructs are investigated as a platform for providing low doses and long exposure times to cells within a three-dimensional environment that can be tuned to mimic in vivo conditions. Uptake of quantum dots by model neural cells was first investigated in a high dose exposure scenario, resulting in a strong concentration-dependent uptake of carboxyl-functionalized quantum dots. Poly(ethylene glycol) hydrogel scaffolds with varying mesh sizes were then investigated for their ability to support cell survival and proliferation. Cells were co-encapsulated with carboxyl-functionalized poly(ethylene glycol) coated quantum dots at a lower dose than is typical for monolayer cultures. Although the quantum dots leach from the hydrogel within 24 hours, they are also incorporated by cells within the scaffold, enabling the use of these constructs in future studies of cell behavior and function.
nanoparticles, cell culture, tissue scaffold, in vitro assay