Facile Fabrication of Microwrinkled Poly(3,4-Ethylenedioxythiophene) Films that Promote Neural Differentiation under Electrical Stimulation.

Although conductive bioelectronic interfaces (BEIs) can allow neural cell culturing while providing electrical stimulation (ES) to the nervous system, there are few simple approaches for the preparation of conductive BEIs with topographical features designed for cell manipulation. In this study, we developed a facile method for fabricating microwrinkled poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) films through spin-coating onto pre-elongated polydimethylsiloxane substrates. The microwrinkles of our PEDOT:PSS films pre-elongated by 20 and 40% had average widths of 6.47 ± 1.49 and 5.39 ± 1.53 µm, respectively. These microwrinkled PEDOT:PSS films promoted the directional ordering of neurite outgrowth of PC12 cells and displayed favorable biocompatibility and outstanding electrochemical properties for long-term ES treatment. When using this BEI platform, the level of PC12 gene expression of Neun was enhanced significantly after 5 days of culturing in differentiation media and under ES, in line with the decreased expression of early phase markers. Therefore, such readily fabricated microwrinkled PEDOT:PSS films are promising candidates for use as BEIs for tissue regenerative medicine.

Rational design of a highly porous electronic scaffold with concurrent enhancement in cell behaviors and differentiation under electrical stimulation.

Conductive polymers (CPs) have received increasing attention as promising materials for studying electrophysiological signals in cell and tissue engineering. The combination of CPs with electrical stimulation (ES) could possibly enhance neurogenesis, osteogenesis, and myogenesis. To date, research has been prioritized on capitalizing CPs as two-dimensional (2D) structures for guiding the differentiation. In contrast, relatively little is conducted on the implementation of 3D conductive scaffolds. In this research, we report the synergic assembly of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and multi-walled carbon nanotubes (MWCNTs) as a biocompatible, electrically conductive, mechanically robust and structurally porous 3D scaffold. To showcase the bioelectronic utilization, a proof-of-concept demonstration of electrically stimulated cell culture under ES is conducted. The ES effects coupled with the 3D scaffold are promising on pheochromocytoma 12 (PC12), a neuronal cell line, and the ES effect on osteogenesis of human adipose-derived stem cells (hASC) was further studied. PC12 cultured on this PEDOT:PSS/MWCNT 3D scaffolds was induced to differentiate toward a more mature neuronal phenotype with the ES treatment. Furthermore, hASC osteogenesis could be highly promoted in this conductive scaffold with ES. Calcium deposition concentration and osteo-differentiated gene markers were significantly higher with ES. The facile assembly of 3D conductive scaffolds sheds light on both platforms for investigating the 3D microenvironment for electrophysiological simulation of cells and tissues under the ES treatment of in vivo tissue engineering.