AbstractEngineering hollow fibers with precise surface microstructures is challenging; yet, essential for guiding cells alignment and ensuring proper vascular tissue function. Inspired by Euplectella sponges, a novel strategy to engineer biomimetic hollow fibers with spiral surface microstructures is developed. Using oxidized bacterial cellulose, bacterial cellulose, and polydopamine, a “brick‐and‐mortar” scaffold is created through precise shear control during microfluidic coaxial spinning. The scaffold mimics natural extracellular matrices, providing mechanical stability and supporting cell growth. In vitro studies show successful co‐culture of endothelial cells (ECs) and smooth muscle cells (SMCs), with SMCs aligning along spiral surface microstructures and ECs forming a confluent inner layer. In vivo implantation confirms biocompatibility, biodegradability, and low immunogenicity. This Euplectella‐inspired scaffold presents a promising approach for vascular tissue engineering and regenerative medicine.