Electronic to ionic transduction of the electric field applied to PEDOT:PSS substrates to the cell cultures on top.

The potential of the electrical double layer (EDL) formed at the interface between cross-linked poly (3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) and phosphate-buffered saline (PBS) was measured with respect to a reference Ag/AgCl electrode, yielding a value of ca. 300 mV, which corresponds to a work function of 4.9 eV. More importantly, we report that the application of a voltage along the PEDOT:PSS substrate induces a modification of the EDL, which mirrors the potential applied to the PEDOT:PSS underneath. This is translated into an ionic electric field, tangential to the interface that images the electric field applied to the PEDOT:PSS. We propose that this modification of the EDL, via application of the electrical field away from the cell culture medium, is at origin of the neural stem cell response to that field, when cultured on top of PEDOT:PSS. Despite the comparatively low value of the Debye length (estimated around 1 nm) with respect to the much larger cell to PEDOT:PSS surface distance, we believe that the perturbation of the EDL is the likely source of the increase of neuronal differentiation of the neural stem cells. We discuss other possible implications of that EDL modulation.

PEDOT:PSS-Coated Polybenzimidazole Electroconductive Nanofibers for Biomedical Applications.

Bioelectricity drives several processes in the human body. The development of new materials that can deliver electrical stimuli is gaining increasing attention in the field of tissue engineering. In this work, novel, highly electrically conductive nanofibers made of poly [2,2'-m-(phenylene)-5,5'-bibenzimidazole] (PBI) have been manufactured by electrospinning and then coated with cross-linked poly (3,4-ethylenedioxythiophene) doped with poly (styrene sulfonic acid) (PEDOT:PSS) by spin coating or dip coating. These scaffolds have been characterized by scanning electron microscopy (SEM) imaging and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. The electrical conductivity was measured by the four-probe method at values of 28.3 S·m-1 for spin coated fibers and 147 S·m-1 for dip coated samples, which correspond, respectively, to an increase of about 105 and 106 times in relation to the electrical conductivity of PBI fibers. Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) cultured on the produced scaffolds for one week showed high viability, typical morphology and proliferative capacity, as demonstrated by calcein fluorescence staining, 4',6-diamidino-2-phenylindole (DAPI)/Phalloidin staining and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] assay. Therefore, all fiber samples demonstrated biocompatibility. Overall, our findings highlight the great potential of PEDOT:PSS-coated PBI electrospun scaffolds for a wide variety of biomedical applications, including their use as reliable in vitro models to study pathologies and the development of strategies for the regeneration of electroactive tissues or in the design of new electrodes for in vivo electrical stimulation protocols.

Effect of Electrical Stimulation Conditions on Neural Stem Cells Differentiation on Cross-Linked PEDOT:PSS Films.

The ability to culture and differentiate neural stem cells (NSCs) to generate functional neural populations is attracting increasing attention due to its potential to enable cell-therapies to treat neurodegenerative diseases. Recent studies have shown that electrical stimulation improves neuronal differentiation of stem cells populations, highlighting the importance of the development of electroconductive biocompatible materials for NSC culture and differentiation for tissue engineering and regenerative medicine. Here, we report the use of the conjugated polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS CLEVIOS P AI 4083) for the manufacture of conductive substrates. Two different protocols, using different cross-linkers (3-glycidyloxypropyl)trimethoxysilane (GOPS) and divinyl sulfone (DVS) were tested to enhance their stability in aqueous environments. Both cross-linking treatments influence PEDOT:PSS properties, namely conductivity and contact angle. However, only GOPS-cross-linked films demonstrated to maintain conductivity and thickness during their incubation in water for 15 days. GOPS-cross-linked films were used to culture ReNcell-VM under different electrical stimulation conditions (AC, DC, and pulsed DC electrical fields). The polymeric substrate exhibits adequate physicochemical properties to promote cell adhesion and growth, as assessed by Alamar Blue® assay, both with and without the application of electric fields. NSCs differentiation was studied by immunofluorescence and quantitative real-time polymerase chain reaction. This study demonstrates that the pulsed DC stimulation (1 V/cm for 12 days), is the most efficient at enhancing the differentiation of NSCs into neurons.

POLYBENZIMIDAZOLE NANOFIBERS FOR NEURAL STEM CELL CULTURE.

Neurodegenerative diseases compromise the quality of life of increasing numbers of the world's aging population. While diagnosis is possible no effective treatments are available. Strong efforts are needed to develop new therapeutic approaches, namely in the areas of tissue engineering and deep brain stimulation (DBS). Conductive polymers are the ideal material for these applications due to the positive effect of conducting electricity on neural cell's differentiation profile. This novel study assessed the biocompatibility of polybenzimidazole (PBI), as electrospun fibers and after being doped with different acids. Firstly, doped films of PBI were used to characterize the materials' contact angle and electroconductivity. After this, fibers were electrospun and characterized by SEM, FTIR and TGA. Neural Stem Cell's (NSC) proliferation was assessed and their growth rate and morphology on different samples was determined. Differentiation of NSCs on PBI - CSA fibers was also investigated and gene expression (SOX2, NES, GFAP, Tuj1) was assessed through Immunochemistry and qPCR. All the samples tested were able to support neural stem cell (NSC) proliferation without significant changes on the cell's typical morphology. Successfully differentiation of NSCs towards neural cells on PBI - CSA fibers was also achieved. This promising PBI fibrous scaffold material is envisioned to be used in neural cell engineering applications, including scaffolds, in vitro models for drug screening and electrodes.