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

Abstract

PurposeThe 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.MethodsRabbit VF fibroblasts (VFF) were treated with different concentrations of SPIONs (20, 40, and 80 μg/cm2), 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.ResultsCellular 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/cm2. Migration and spreading were not significantly influenced by SPION treatment up to 80 μg/cm2.Discussion and ConclusionTo 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.

Nanoparticle–Cell Interaction: A Cell Mechanics Perspective

“…Cells treated with SPIONs up to 20 µg cm −2 showed no significant alteration of adhesion for rabbit vocal fold fibroblasts (VFF). However, exposure of 40 and 80 µg cm −2 SPIONs resulted in a significant decrease in VFF adhesion …”

“… Cell mechanics plays important role in organism development, physiology and diseases. Ag, alumina, HA, SPIONs, SiO 2 , and TiO 2 NPs can induce detrimental effects on cell adhesion including destruction of tight and adherens junctions and modulation of cell–ECM adhesion (i.e., reduction and maturation of FAs). Interaction of Ag, HA, SPIONs, TiO 2 , and ZnO NPs and cytoskeletal proteins (actin and tubulin) can promote destabilization of the cytoskeleton including remodeling and destruction of MT and F‐actins structures. Cell stiffness increases due to the presence of Au and SiO 2 NPs NPs can retard cell migration through destruction of the cytoskeleton, increase in adhesions and modulating the expression of cell migration‐related proteins/molecules …”

3D bioprinting of nanoparticle-laden hydrogel scaffolds with enhanced antibacterial and imaging properties

“…Interestingly, there were no significant decreases in cell viability at day 7 for the NIH3T3 cells in contrast to the HUVEC results, suggesting greater tolerance of the fibroblast line against the NP-associated cytotoxic effects (as reported before ( Kong et al., 2011 ; Sahu et al., 2016 )). Of note, in both EC and fibroblast cells, clathrin and caveolae-mediated endocytosis are the common receptors used for the uptake of NPs, including the SPIONs ( Behzadi et al., 2017 ; Pottler et al., 2017 ; Rejman et al., 2004 ; Salingova et al., 2019 ). Thus, the SPION uptake in these cells can be regulated by manipulating these cell receptor pathways, as well as tuning the NP properties (e.g., size, protein corona, and surface charge) ( Behzadi et al., 2017 ; Rejman et al., 2004 ).…”

Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

“…Dürr et al isolated vocal fold fibroblasts from rabbit laryngeal heads and achieved their magnetization by incorporating IONPs [ 551 ]. The same group characterized the cellular effects of IONP uptake and demonstrated feasibility for magnetic cell guidance and possible generation of magnetic tissue-engineered 3D vocal fold constructs [ 552 , 553 ].…”