Cryogenic Biomanufacturing: Principle, Technology, and Applications

ABSTRACT Conventional biomanufacturing faces critical translational bottlenecks, including limited clinical availability of functional tissues, inability to achieve long‐term storage, and structural collapse during large‐scale fabrication. Cryogenic biomanufacturing (CBM) ‐leveraging controlled phase transitions and ice‐crystal templating‐provides transformative solutions by enabling precise multi‐scale architectures, structural stabilization of volumetric constructs, and cryopreservation of cell‐laden products. This review elucidates CBM's core principles, emphasizing its unique capacity to arrest metabolic activity while directing hierarchical porosity through ice‐growth kinetics. We systematically analyze three cornerstone technologies: freeze casting for anisotropic microchannel scaffolds, freeze spinning for biomimetic fibrous matrices, and cryogenic 3D bioprinting for high‐fidelity, cell‐compatible macroscale tissues. Applications in neural regeneration, bone repair, and ex vivo disease modeling demonstrate CBM's versatility. Finally, we critically evaluated the challenges related to cryoprotectant toxicity, temperature control systems, and the precise control of porous structures, paving the way for clinical translation and the establishment of organ banks.