Impact of Superparamagnetic Iron Oxide Nanoparticles on Vocal Fold Fibroblasts: Cell Behavior and Cellular Iron Kinetics

Marina Pöttler, Anna Fliedner, Eveline Schreiber, Christina Janko, Ralf Philipp Friedrich, Christopher Bohr, Michael Döllinger, Christoph Alexiou, Stephan Dürr

The voice is the most important instrument of communication. Tissue defects in the vocal fold (VF) area lead to serious reduction in quality of life, but thus far, no satisfactory VF implant exists. Therefore, we aim to establish a functional VF implant in a rabbit model by magnetic tissue engineering (MTE) using superparamagnetic iron oxide nanoparticles (SPION). Hence, iron quantification over time as well as cell behavior studies upon SPION treatment are of great importance. Rabbit VF fibroblasts (VFF) were treated with different concentrations of SPIONs (20, 40, and 80 μg/cm(2)), and iron content was examined for up to 40 days using microwave plasma-atom emission spectroscopy. The effects of SPION treatment on VFF (adhesion, spreading, and migration), which are important for the formation of 3D structures, were tested. Cellular SPION quantification revealed that there was no residual iron remaining in VFFs after 40 days. SPIONs had a dose-dependent effect on cell adhesion, with good tolerability observed up to 20 μg/cm(2). Migration and spreading were not significantly influenced by SPION treatment up to 80 μg/cm(2). To develop 3D structures, cell behavior should not be affected by SPION uptake. After 40 days, cells were free of iron as a result of metabolism or rarefication during cell division. Cell functions including adhesion, spreading, and migration were proven to be intact in a dose-dependent manner after SPION treatment, suggesting a safe usage of MTE for voice rehabilitation. Our results thus constitute a solid basis for a successful transfer of this technique into 3D constructs, in order to provide an individual and personalized human VF implant in the future.