Ultra-Compliant and Biodegradable Stem Cell-Embedded Hydrogel Microelectrode Arrays Applied for Combined Neural Signal Diagnosis, Electrically Neuromodulation and Cell Therapy

Biohybrid neural interfaces (BHNIs) are a new class of neuromodulating devices that integrate neural microelectrode arrays (MEAs) and cell transplantation to improve treatment of nerve injuries and disorders. However, current BHNI devices are made from abiotic materials that are usually bio-passive, non-biodisintegratable, or rigid, which restricts encapsulated cell activity and host nerve reconstruction and frequently leads to local tissue inflammation. Herein, we propose the first MEA composed of all biodisintegratable hydrogel tissue scaffold materials with synergistic performances of tissue conformal adhesiveness, MEA technologies, tissue scaffolding and stem cell therapy on a time scale appropriate for nerve tissue repair. The device substrate is made of an enzyme-crosslinked gelatin/silk (GS) hydrogel with adhesiveness and controllable degradability that benefit nerve tissue integration and neural progenitor cell (NPC) transplantation. MEA circuits composed of graphene oxide (GO)/PEDOT/gelatin-based ECHs were designed with a double-crosslinked architecture to confirm robust ionic/electroconductive properties. With seamless lamination around peripheral nerve fibers, the device permits successive neural signal monitoring for wound condition evaluation, while demonstrating synergistic effects of spatiotemporally controlled electrical stimulation and cell transplantation to accelerate restoration of motor function.