Nanoengineered extrusion-aligned tract bioprinting enables functional repair of spinal cord injuries.

Abstract

Spinal cord repair demands biomaterials that replicate the aligned axonal architecture and mechanical softness of native tissue. However, most current scaffolds fail to support three-dimensional alignment and neuronal differentiation of human neural stem cells (hNSCs) in hydrated, low-stiffness environments. Here, we present NEAT (nanoengineered extrusion-aligned tract), a shear-stress-driven 3D bioprinting strategy that utilizes norbornene-functionalized collagen (NorCol) to generate highly aligned, mechanically stable hydrogels without post-processing. NEAT preserves the native triple-helical structure of collagen, supports hierarchical fibrillar organization, and enables rapid photopolymerization for long-term culture (>8 weeks). When encapsulated in NEAT constructs, human NSCs exhibited enhanced alignment and accelerated neuronal differentiation, guided by the optimized fibrillar architecture. In a rat model of complete spinal cord transection, NEAT implants promoted robust axonal reconnection, synapse formation, and significant functional locomotor recovery. This strategy bridges topographical control, cellular programming, and functional integration, providing a powerful platform for neural tissue engineering and spinal cord regeneration.