Multifunctional Cell-Culture-Platforms Integrated with Soft Electronics for Electrophysiological Applications

Abstract

Compared to conventional electronic devices, soft electronics offer the proper mechanical properties similar to native tissues and cells. This feature provides not only the promotion of cellular activities during culturing cells in vitro, but also the enhancement of biological interfaces between soft electronics and curvilinear surfaces of target organs in vivo. The high-quality interface enables effective monitoring and stimulation of electrophysiological signals. In this thesis, fabrications of three types of cell-culture-platforms and those applications are introduced. Components of all electronics are fabricated based on soft nanomaterials such as inorganic or carbon nanomaterials, and those electronics are transferred onto a biocompatible polymer substrate. Firstly, soft cell-culture-platform is designed to prepare C2C12 myoblasts sheet for transfer printing and treating the damaged muscle tissue. The platform is instrumented with stretchable nanomembrane sensors for in situ monitoring of cellular physiological characteristics during proliferation and differentiation, and with graphene nanoribbon cell aligners for guiding the unidirectional orientation of plated cells, whose system modulus is matched with target tissues. Furthermore, a high-yield transfer printing mechanism can deliver cell sheets for scaffold-free, localized cell therapy in vivo. Secondly, multifunctional cell-sheet-graphene hybrid is developed as stretchable and transparent medical device, which can be implanted in vivo to form a high-quality biotic/abiotic interface. The hybrid is composed of C2C12 myoblasts sheet on buckled, mesh-patterned graphene electrodes. The graphene electrodes monitor and stimulate the C2C12 myoblasts in vitro, serving as a smart cell culture substrate that controls their aligned proliferation and differentiation. This stretchable and transparent cell-sheet-graphene hybrid can be transplanted onto the target muscle tissue, record electromyographical signals, and stimulate implanted sites electrically and/or optically in vivo without any immune responses. Additional cellular therapeutic effect of the cell-sheet-graphene hybrid is obtained by the integrated C2C12 myobalsts sheet. Finally, electronic-cell-culture-platform is fabricated to provide multifunctionalities by integrating various types of electronics for monitoring and stimulating important metabolic conditions of culturing cells. This platform is based on an array of soft electronics composed of four types of sensors and two types of stimulators, which is transferred onto a biocompatible polymer substrate designed by a 3D printer. The sensors and stimulators can monitor and regulate the behaviors and activities of the cells cultured on the large area surface of the platform. The multi-layer system of the platform enable to monitor and stimulate the activities of numerous cells effectively without sacrificing any culturing cells.