Stress‐Resistant Plant Cell‐Wall Inspired Cell Armor Enables Red Blood Cell Lyophilization

ABSTRACT Lyophilization offers an attractive route for ambient‐temperature storage of biological systems by eliminating cold‐chain dependence and suppressing solution‐phase degradation. However, lyophilizing mammalian cells remains challenging due to their vulnerability to coupled stresses, including ice‐induced mechanical injury and membrane destabilization during freezing and dehydration. In nature, stress‐resistant plant cells survive extreme conditions through multifunctional cell walls. Inspired by their natural survival strategies, we engineer an artificial membrane armor (AMA) that enables efficient lyophilization of red blood cells (RBCs). This biomimetic AMA integrates a nanoporous zeolitic imidazolate framework (ZIF‐8) for mechanical support, a water‐retentive polymer matrix for hydration retention and colloidal stabilization, and Zn 2 + coordination preserves membrane fluidity and suppresses freeze‐ and dehydration‐driven membrane phase transitions. Through synergistic interfacial protection, the AMA effectively buffers coupled stresses associated with lyophilization, enabling ∼95% post‐rehydration recovery of RBCs using an ultra‐low protectant content (<5 wt%) together with an ambient shelf‐life of at least 3 months, unachievable with previous methods. Furthermore, the rehydrated RBCs preserve their native morphology, membrane mechanics, metabolic activity, oxygen transport capability, and in vivo circulation behavior. This work establishes a bioinspired interfacial engineering strategy for transferring desiccation tolerance from plants to mammalian cells, advancing ambient‐temperature biostorage of sensitive living systems.