Neuronal Differentiation of Embryonic Stem Cell Derived Neuronal Progenitors Can Be Regulated by Stretchable Conducting Polymers

Abstract

Electrically conducting polymers are prospective candidates as active substrates for the development of neuroprosthetic devices. The utility of these substrates for promoting differentiation of embryonic stem cells paves viable routes for regenerative medicine. Here, we have tuned the electrical and mechanical cues provided to the embryonic stem cells during differentiation by precisely straining the conducting polymer (CP) coated, elastomeric-substrate. Upon straining the substrates, the neural differentiation pattern occurs in form of aggregates, accompanied by a gradient where substrate interface reveals a higher degree of differentiation. The CP domains align under linear stress along with the formation of local defect patterns leading to disruption of actin cytoskeleton of cells, and can provide a mechano-transductive basis for the observed changes in the differentiation. Our results demonstrate that along with biochemical and mechanical cues, conductivity of the polymer plays a major role in cellular differentiation thereby providing another control feature to modulate the differentiation and proliferation of stem cells.

Stretchable Conductive Polymers and Composites Based on PEDOT and PEDOT:PSS

“…An advantage of this approach was that the surface could be patterned by selective photo‐crosslinking of PEGDA using masks, although the PDMS still required activation with an oxygen plasma to allow the adhesion of PEGDA. Nonsilicone‐based elastomers have also been used as substrates for PEDOT:PSS including SEBS, poly(ethylene terephthalate) (PET), and polyimide (PI) . In most cases, PEDOT:PSS supported on elastomers led to devices with a limited stretchability due to the intrinsic brittleness of the conductive polymer.…”

Electrical Stimulation Using Conductive Polymer Polypyrrole Promotes Differentiation of Human Neural Stem Cells: A Biocompatible Platform for Translational Neural Tissue Engineering

“…For example, electrostimulation via CPs may be useful to facilitate differentiation of human stem cells to neuronal lineage, with CP substrates able to support neuronal differentiation of murine embryonic stem cells, and electrical stimulation predisposes cells arising from murine embryoid bodies (EBs) to assume a neuronal fate in vitro, with no GFAP-immunoreactive cells. [1][2] Not surprisingly, endogenous electric fields occur in vivo in the form of transepithelial cellular potentials or neuronal field potentials, and are important during embryonic and fetal development, as well as wound healing and tissue regeneration. 3,5 Disturbances to environmental electric fields cause aberrant development.…”

Morphology and electrostatics play active role in neuronal differentiation processes on flexible conducting substrates

“…In a recent work from our laboratories, we demonstrated the effect of electroactivity and varying charge distribution produced by straining PEDOT:PSS (Poly[3,4 -et hylened iox y t hiophene] poly[styrenesulfonate]) coated SEBS (styrene ethylene butylene styrene) substrates on the differentiation of mouse D3 ES-NPs (embryonic stem cell derived neuronal progenitors). 15 We also showed that the cellular distribution over the substrate is affected by the strain applied on the substrates. The work also emphasized on the reorganization of the actin fibers due to the electroactivity of the substrates and the strain applied on them.…”

“…4,[11][12][13] Besides these features, it has also been realized that introduction of electronic conductivity can further provide a specific handle to control the differentiation or other physiological properties of the cell. 14,15 In vitro studies of the physiological properties of cells have shown that they can integrate and respond to a variety of biological, chemical and physical cues provided to them by the extra-cellular matrix. 16 Cells bind to the ECM via focal adhesion complexes which are formed by the recruitment of many protein complexes and clustering of integrins.…”