Hydrogel Electromagnetic Biohybrid Systems Direct Neural Morphogenesis across Central and Peripheral Systems

Abstract

Biohybrid materials that integrate structural and bioelectronic cues across scales offer new routes to regulate neural development and repair. We present a hybrid, hydrogel-electromagnetic stimulation platform with a 3D hierarchically anisotropic structure, combining FLight bioprinted hydrogel microfilaments with a melt-electrowritten wireless electromagnetic stimulation system, to guide neural morphogenesis across central and peripheral systems at cellular and tissue scale. In the central nervous system, the soft microfilaments selectively promoted healthy, white-matter-like neurite extension rather than glioblastoma-derived outgrowth in human cortical brain tissues, while the electrically stimulation further enhanced the hippocampal neurosphere networking along the microfilaments. As a peripheral nerve conduit, the system directs dorsal root ganglion alignment in vitro and, in rat sciatic defects, drives a coordinated pro-regenerative response that improves axonal guidance, remyelination, and functional recovery. This multiscale biohybrid strategy demonstrates how synergistic integration of soft biomaterials and systematic, wireless bioelectric cues can non-invasively regulate neural morphogenesis, establishing new design principles for next-generation bioelectronic interfaces and regenerative medicine.