Generation of Human iPSC-Derived Neurons on Nanowire Arrays Featuring Varying Lengths, Pitches, and Diameters

Nanowire (NW) arrays interfaced with biological cells have been demonstrated to be potent tools for advanced applications such as sensing, stimulation, or drug delivery. Many implementations, however, have so far only been studied with rather robust basic cell models. Here, the generation of human induced pluripotent stem cell (iPSCs)-derived neurons is presented on various types of NW arrays. Specifically, combinations of three NW lengths (1, 3, and 5 mu m), three array pitches (1, 3, and 5 mu m), and two NW diameters (thin/thick pairs, 270-600 nm/590-1070 nm) are being utilized. The cell/NW interactions range from fakir-like states to NW-encapsulating states depending on the array characteristics. The cultures show equal proportions of neuronal marker-positive cells after 8-9 days of terminal differentiation on the NW arrays (14-15 days in total) compared to planar controls. In addition, the neurons are functional with similar kinetics of the action potentials highlighting the equivalence of the NW arrays for neuronal differentiation. In the future, stem cell research and regenerative medicine might substantially benefit from further functionalized NW arrays enabling the well-established mechanisms such as NW-mediated in vitro gene editing or intracellular delivery of biomolecules to further control and/or to enhance neuronal differentiation.