Transcriptomic analysis reveals the heterogeneous role of conducting films upon electrical stimulation

Central nervous system (CNS) injuries and neurodegenerative diseases have markedly poor prognoses and can result in permanent dysfunction due to the general inability of CNS neurons to regenerate. Differentiation of transplanted stem cells has emerged as a therapeutic avenue to regenerate tissue architecture in damaged areas. Electrical stimulation is a promising approach for directing the differentiation outcomes and pattern of outgrowth of transplanted stem cells, however traditional inorganic bio-electrodes can induce adverse effects such as inflammation. Here, we demonstrate the implementation of two organic thin films, a polymer/reduced graphene oxide nanocomposite (P(rGO)) and PEDOT:PSS, that have favorable properties for implementation as conductive materials for electrical stimulation, as well as an inorganic indium tin oxide (ITO) conductive film. Transcriptomic analysis revealed that electrical stimulation improved neuronal differentiation of SH-SY5Y cells on all three films, with the greatest effect for P(rGO). Unique material- and electrical stimuli-mediated effects were observed, associated with differentiation, cell-substrate adhesion, and translation. Our work demonstrates that P(rGO) and PEDOT:PSS are highly promising organic materials for the development of biocompatible, conductive scaffolds that will enhance electrically-aided stem cell therapeutics for CNS injuries and neurodegenerative diseases. Overall design: We implemented three classes of materials, a polymer/reduced graphene oxide nanocomposite (P(rGO)), poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), and indium tin oxide (ITO) as conductive films for electrical stimulation of SH-SY5Y cells during differentiation. RNA-seq was performed to examine the effects due to both the conductive materials and electrical stimulation.