Shear‐Stimulated Bioprinting Enables Anisotropic and Multi‐Region Neural Bioconstruct

ABSTRACT Engineering neural tissues with controlled cellular organization remains challenging due to the limited ability of conventional bioprinting to regulate cellular anisotropy. Here, we present a blade‐assisted shear‐stimulated bioprinting strategy for fabricating anisotropic and multi‐region neural bioconstructs. A blade integrated near the nozzle generated a defined shear field during extrusion, inducing directional alignment of human neural progenitor cells (hNPCs) within a GelMA/HA/Matrigel bioink. Rheological and process analyses identified shear conditions that maximized cellular alignment while maintaining high viability. Shear‐stimulated bioconstructs exhibited enhanced cytoskeletal organization, neurite extension, and neuronal maturation compared with conventional extrusion printing. Furthermore, the system enabled fabrication of multi‐region cellular–acellular–cellular (CAC) neural architectures, in which the acellular interfacial region prevented uncontrolled cellular intermixing while promoting directed neurite bridging and enhanced neuronal connectivity. Mechanistic analyses suggested activation of mechanosensitive signaling pathways associated with cytoskeletal remodeling and neurogenesis. Collectively, these findings demonstrate that process‐defined shear stimulation can program cellular organization and multi‐region neural architectures during bioprinting, providing a promising platform for engineering structurally organized neural tissues for in vitro applications.