A DNA-logic artificial cell wall for dimethyl sulfoxide-free cryopreservation and post-thaw proliferation.

Abstract

Cell cryopreservation is fundamental to modern biomedicine but is constrained by the cytotoxicity of conventional cryoprotectants like dimethyl sulfoxide and the frequent impairment of cellular function after thawing. Here, we introduce a biocompatible DNA-logic artificial cell wall, engineered by integrating a programmable DNA-logic framework with a calcium alginate hydrogel. This platform simultaneously addresses the two main challenges in cryopreservation: physical damage from ice crystals and poor biological recovery after thawing. The hydrogel physically shields cells from ice injury, while the programmable DNA system enables cell-type-specific recognition, activates intracellular signaling pathways, promotes post-thaw functional recovery, and inhibits ice growth. By merging mechanical protection with biological activation, this dual-mechanism strategy significantly improves cell survival and functional restoration after thawing. This approach resolves the traditional compromise between structural preservation and functional recovery, offering a promising route toward high-fidelity cell preservation and therapy.