Biocompatibility of ALD Coatings on Nano- and Microstructures: Cell Viability Studies of Murine and Human Induced Stem Cell-Derived Neurons
Micro- and nanostructured substrates form a powerful tool for building next-generation medical devices. Especially, controlled interaction of neuronal cells with the substrate allow for sensing, stimulation, gene transfection and drug delivery paving the way for developing novel conceptual devices such as integrated solar cell nanowires for retina implants, artificial bio-computing circuits, and model systems for neurodegenerative diseases, to name a few.
One key prerequisite is the biocompatibility of the surface to allow for fully functional neuronal outgrowth and cell viability. However, functional nano- and microstructured devices are often based on semiconductors or polymers which potentially contain toxic materials. During cell culturing, cellular uptake of harmful components may influence the stem cell differentiation process, the neuronal outgrowth or the electrophysiological properties, and can ultimately induce the cell death.
Atomic Layer Deposition (ALD)—basing on sequential self-limiting gas-solid-surface reactions—is ideally suited to conformally coat micro- and nanostructures. Often ALD of standard oxides, such as silica, titania, and alumina, are claimed to be biocompatible; however, data reporting on cell viability are mostly missing in ALD thin film studies.
Herein, we present cell viability studies on a variety of micro- and nanostructured substrates coated by ALD with standard oxides of varying thicknesses and subsequently used for neuronal cell cultivation. The determined cell viabilities are compared to plain Petri dish control substrates.
In detail, we investigate ALD-coated 3D-printed cavity structures  and freestanding nanowire arrays  for outgrowth of murine and human induced stem cell-derived neurons. We show that cell viability—utilizing a viability assay with subsequent confocal microscopy—and full electrophysiological integrity—investigated by patch-clamping of individual cells—is maintained on the micro- and nanostructures.
Our results suggest that biocompatible thin film coatings can be in fact achieved by ALD. This property in combination with the ability of conformal coating renders ALD to an economically feasible key technique for application in micro- and nanostructured lab-on-a-chip devices interfaced with human cells.
 Fendler et al., Adv. Biosystems 3 (2019), 1800329
 Harberts et al., RSC Advances 9 (2019), 11194