3D-printed biodegradable scaffolds stand out as the most promising solutions for regeneration of human tissues or organs. However, the existing 3D-printed scaffolds commonly suffer from weak cell-scaffold interactions and insufficient cell organizations due to the limited resolution of the 3D-printed features. By combining 3D printing, electrospinning, and unidirectional freeze-casting, the hybrid-manufactured composite scaffold features mechanically robust frameworks and aligned nanofibrous architectures. This pioneering approach provides stable structural supports and cell-friendlymicroenvironments for directed cell infiltration and enhanced tissue regeneration.