Electrical Stimulation with a Conductive Polymer Promotes Neurite Outgrowth and Synaptogenesis in Primary Cortical Neurons in 3D

Abstract

Deficits in neurite outgrowth and synaptogenesis have been recognized as an underlying developmental aetiology of psychosis. Electrical stimulation promotes neuronal induction including neurite outgrowth and branching. However, the effect of electrical stimulation using 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. This study examined the effect of 3D electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical stimulation improved neurite outgrowth in 3D neuronal cultures from both wild-type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95 were elevated under 3D electrical stimulation. Interestingly, 3D electrical stimulation also improved neural cell aggregation as well as the expression of PSA-NCAM. Our findings suggest that the 3D electrical stimulation system can rescue neurite outgrowth deficits in a 3D culturing environment, one that more closely resembles the in vivo biological system compared to more traditionally used 2D cell culture, including the observation of cell aggregates as well as the upregulated PSA-NCAM protein and transcript expression. This study provides a new concept for a possible diagnostic platform for neurite deficits in neurodevelopmental diseases, as well as a viable platform to test treatment options (such as drug delivery) in combination with electrical stimulation.

Human Neural Tissues from Neural Stem Cells Using Conductive Biogel and Printed Polymer Microelectrode Arrays for 3D Electrical Stimulation

“…Several recent reports have shown that electrical stimulation (ES) can be used to modulate fate determination of differentiating human neural stem cell (NSCs), including the promotion of neuronal versus glial cell induction and increased neuritogenesis . From our own research, we have demonstrated the use of biphasic electrical current via a conductive polymer (CP), polypyrrole, to promote neurite outgrowth and synaptogenesis of rat primary cortical neurons, as well as differentiation of human NSCs to neurons with longer neurites and increased branching, and concomitant lower induction of neuroglia …”

Enhancing the Conductivity of Cell-Laden Alginate Microfibers With Aqueous Graphene for Neural Applications

“…Presented here are cell-laden graphene-alginate hydrogels in the form of microfibrous scaffoldings. These fibers have the potential to deliver and receive electrical signals to cells, thereby showing great promise in a wide number of fields, as these mechanisms are known to affect cell behaviors such as differentiation, orientation, mobility, and more (Sirivisoot et al, 2014;Wang et al, 2017;Osipova et al, 2018;Zhang et al, 2018). Current conductive hydrogels in biomedical fields take the form of membranes (Escalona et al, 2012), gels (Liu et al, 2016;Bu et al, 2018), or films (Dong et al, 2016;Liu et al, 2017;Wang et al, 2018).…”

“…Hydrogel scaffolds create physiologically relevant platforms for studying cell behavior, and modifications such as increased conductivity may allow for the elucidation of electrical cell-to-cell communication mechanisms within neuronal cell cultures. Existing research created hydrogels with enhanced conductivity to deliver electrical stimulation to cells to study or control cell response, viability, and regeneration potentials (Mohanty et al, 2013;Sirivisoot et al, 2014;Mawad et al, 2016;Inal et al, 2017;Wang et al, 2017;Niemczyk et al, 2018;Osipova et al, 2018;Zhang et al, 2018). However, conductive biocompatible hydrogels remain underutilized as 3D electro-sensing cell culture scaffoldings (Acar et al, 2014).…”

Organic Bioelectronics: Using Highly Conjugated Polymers to Interface with Biomolecules, Cells, and Tissues in the Human Body

“…Polypyrrole, polyaniline, and PEDOT:PSS guided nerve growth has been studied extensively, with interfaces permitting enhanced control over neurite outgrowth and orientation. [ 154,164,346 ] Zhang et al. electrically stimulated cells cultured on polypyrrole, demonstrating that this could reduce the effect of specific gene knockouts that otherwise impair neurite growth ( Figure ).…”