Fabrication of Soft Tissue Scaffold-Mimicked Microelectrode Arrays Using Enzyme-Mediated Transfer Printing

Hydrogels are the ideal materials in the development of implanted bioactive neural interfaces because of the nerve tissue-mimicked physical and biological properties that can enhance neural interfacing compatibility. However, the integration of hydrogels and rigid/dehydrated electronic microstructure is challenging due to the non-reliable interfacial bonding, whereas hydrogels are not compatible with most conditions required for the micromachined fabrication process. Herein, we propose a new enzyme-mediated transfer printing process to design an adhesive biological hydrogel neural interface. The donor substrate was fabricated via photo-crosslinking of gelatin methacryloyl (GelMA) containing various conductive nanoparticles (NPs), including Ag nanowires (NWs), Pt NWs, and PEDOT:PSS, to form a stretchable conductive bioelectrode, called NP-doped GelMA. On the other hand, a receiver substrate composed of microbial transglutaminase-incorporated gelatin (mTG-Gln) enabled simultaneous temporally controlled gelation and covalent bond-enhanced adhesion to achieve one-step transfer printing of the prefabricated NP-doped GelMA features. The integrated hydrogel microelectrode arrays (MEA) were adhesive, and mechanically/structurally bio-compliant with stable conductivity. The devices were structurally stable in moisture to support the growth of neuronal cells. Despite that the introduction of AgNW and PEDOT:PSS NPs in the hydrogels needed further study to avoid cell toxicity, the PtNW-doped GelMA exhibited a comparable live cell density. This Gln-based MEA is expected to be the next-generation bioactive neural interface.