Nerve injuries in the central or peripheral nervous system threaten human health and hinder social development, and effectively repairing or regenerating nerve tissues remains a huge challenge. The rise of tissue engineering strategies has brought new light for this. Similar to the extracellular matrix, biomimetic three-dimensional (3D) porous scaffolds can provide biophysical and biochemical cues to guide cell behaviors and support tissue growth. Here, we prepared a hybrid cobalt-doped alginate/waterborne polyurethane 3D porous scaffold with nano-topology of a "coral reef-like" rough surface via two-step freeze-drying. The experimental results demonstrated that the "coral reef-like" rugged surface topology and bioactive cobalt dopant synergistically promote the neurite outgrowth and up-regulate the synaptophysin expression of neuron-like cells PC12 on the scaffold. Furthermore, the scaffold notably relieved the inflammatory response of microglial cells BV2 with the transformation from pro-inflammatory (M1) to anti-inflammatory (M2) phenotype. We believe that this 3D porous scaffold offers bright design inspiration for neural tissue engineering scaffolds and holds potential applications in nerve repair.