In this study, a novel method using microfluidics and graphene transfer via polymer casting was developed to create biodegradable and implantable microcircuits to control stem cell differentiation for peripheral nerve regeneration. Conductive graphene ink was administered to preformed microchannels using a microfluidic approach and the obtained patterns were transferred to desired polymeric substrates via simple polymer casting. The structural and mechanical properties of the developed flexible circuits were characterized via SEM, XPS and Raman Spectroscopy along with electrical stability and conductivity. For in vitro cell culture tests, mesenchymal stem cells (MSCs) were seeded on the circuits to evaluate their attachment, growth and proliferation. Different electrical stimuli parameters (100 mV at 50 Hz for 10 min per day for 10 days, based on our initial studies) were applied to transdifferentiate MSCs into Schwann cell (SC)-like phenotypes. The degree of transdifferentiation and paracrine activity were characterized via immunocytochemistry (ICC), RT-PCR, ELISA assays and co-culture with PC12-TrkB cells. We successfully developed porous and 3D microstructured poly-l-lactic acid (PLLA)-graphene-based biodegradable, implantable and flexible electronic microcircuits. The results indicated 100% transfer of the graphene patterns with small feature size (as low as 5 μm) on the polymer substrate. The formed graphene patters had sheet resistance of 1 kΩ/sq and maintained their stability and conductivity after multiple bending and washing cycles. In vitro cell culture studies indicated that MSCs attached both on the PLLA surface and graphene micropatterns and grown and proliferated for at least 10 days. ICC analysis showed 90% immunolabeling of SC markers (s100, s100β and P75) indicating successful transdifferentiation, which were further supported by detection of higher levels of nerve growth factor and myelin basic protein in RT-PCR and ELISA assays as well as co-culture tests with PC12-TrkB cells. Overall, this method is facile and versatile, which does not require harsh postprocessing and enables the use of different natural/synthetic biodegradable polymers with precise control of 3D microstructural and mechanical properties as well as high resolution graphene patterns. The fabricated devices can be used to control stem cell behavior for neural tissue regeneration.

Flexible electronic biointerfaces for neural tissue engineering

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.