All Biodisintegratable Hydrogel Biohybrid Neural Interfaces with Synergistic Performances of Microelectrode Array Technologies, Tissue Scaffolding, 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, the first MEA composed of all disintegratable 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 is proposed. In particular, the MEA conductive tracks are made from extracellular matrix (ECM)-based double-cross-linked dual-electrically conductive hydrogel (ECH) systems with robust tissue-mimicking chemical/physical properties, electrical conductivity, and an affinity for neural progenitor stem cells. Meanwhile, the MEA hydrogel substrate prepared from transglutaminase-incorporated gelatin/silk precursors simultaneously promotes gelation and interfacial adhesion between all MEA stacks, leading to rapid and scalable device integration. When the full hydrogel MEA is subjected to various mechanical stimuli and moisture, it is structurally stable with a low impedance (4 ± 3 kΩ) comparable to a recently reported benchmark. 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. This BHNI is completely degraded by 1 month thus eliminating the need for surgical retrieval to stably remain, interact, and further fuse with host tissues, successfully exhibiting compatible integration of biology and an implanted electrical system.