Graphene-based materials (GBMs) have displayed tremendous promise for use as neurointerfacial substrates as they enable favorable adhesion, growth, proliferation, spreading, and migration of immobilized cells. This study reports the first case of the differentiation of mesenchymal stem cells (MSCs) into Schwann cell (SC)-like phenotypes through the application of electrical stimuli from a graphene-based electrode. Electrical differentiation of MSCs into SC-like phenotypes is carried out on a flexible, inkjet-printed graphene interdigitated electrode (IDE) circuit that is made highly conductive (sheet resistance < 1 kΩ/sq) via a postprint pulse-laser annealing process. MSCs immobilized on the graphene printed IDEs and electrically stimulated/treated (etMSCs) display significant enhanced cellular differentiation and paracrine activity above conventional chemical treatment strategies [≈85% of the etMSCs differentiated into SC-like phenotypes with ≈80 ng mL of nerve growth factor (NGF) secretion vs. 75% and ≈55 ng mL for chemically treated MSCs (ctMSCs)]. These results help pave the way for in vivo peripheral nerve regeneration where the flexible graphene electrodes could conform to the injury site and provide intimate electrical simulation for nerve cell regrowth.
In this study, a novel method based on the transfer of graphene patterns from a rigid or flexible substrate onto a polymeric film surface via solvent casting was developed. The method involves the creation of predetermined graphene patterns on the substrate, casting a polymer solution, and directly transferring the graphene patterns from the substrate to the surface of the target polymer film via a peeling-off method. The feature sizes of the graphene patterns on the final film can vary from a few micrometers (as low as 5 µm) to few millimeters range. This process, applied at room temperature, eliminates the need for harsh post-processing techniques and enables creation of conductive graphene circuits (sheet resistance: ~0.2 kΩ/sq) with high stability (stable after 100 bending and 24 h washing cycles) on various polymeric flexible substrates. Moreover, this approach allows precise control of the substrate properties such as composition, biodegradability, 3D microstructure, pore size, porosity and mechanical properties using different film formation techniques. This approach can also be used to fabricate flexible biointerfaces to control stem cell behavior, such as differentiation and alignment. Overall, this promising approach provides a facile and low-cost method for the fabrication of flexible and stretchable electronic circuits.
In this study, a simple microfluidic method, which can be universally applied to different rigid or flexible substrates, was developed to fabricate high-resolution, conductive, 2D and 3D microstructured graphenebased electronic circuits. The method involves controlled and selective filling of microchannels on substrate surfaces with a conductive binder-free graphene nanoplatelets (GNP) solution. The ethanolthermal reaction of GNP solution at low temperatures (~75 °C) prior to microchannel filling (pre-heating) further reduces GNP, enhances conductivity, reduces sheet resistance (~0.05 kΩ sq-1), enables room temperature fabrication and eliminates harsh post-processing, which makes this fabrication technique compatible with degradable substrates. This method can also be used in combination with 3D printing to fabricate 3D circuits. The feature sizes of the graphene patterns can range from a few micrometers (down to ~15 µm in width and ~5 µm in depth) to a few millimeters and use very small amounts of GNP solution (~2.5 mg of graphene to obtain ~0.1 kΩ sq-1 of sheet resistance for 1 cm2). This microfluidic approach can also be implemented using other conductive liquids, such as conductive graphene-silver solutions. This technology has the potential to pave the way for low-cost, disposable and biodegradable circuits for a range of electronic applications including near field communication antennas, pressure or strain sensors.
Jonathan C. Claussen, Surya Mallapragada, Donald S. Sakaguchi, and co‐workers demonstrate how the application of electrical stimuli via an inkjet printed graphene electrode can induce the differentiation of mesenchymal stem cells (MSCs) into Schwann cell (SC)‐like phenotypes in article number 1601087. This thin and flexible graphene‐based electrode could potentially be used as an implantable neural interface material for peripheral nerve regeneration.
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