Cryoprotectants play a key role in cell cryopreservation because they can reduce cryoinjuries to cells associated with ice formation. To meet the clinical requirements of cryopreserved cells

cryoprotectants should be biocompatible

highly efficient and easily removable from cryopreserved cells. However

integration of these properties into one cryoprotectant still remains challenging. Herein

three biocompatible neutral amino acids

including β-alanine

γ

-aminobutyric acid and ε-aminocaproic acid

are first reported to have the potential as such ideal cryoprotectants. The results demonstrate that they can inhibit ice formation and reduce osmotic stress to provide extracellular and intracellular protection

thereby ensuring high cryopreservation efficiency for both anuclear and nucleated cells. More importantly

due to the remarkable osmotic regulation ability

the neutral amino acids can be rapidly removed from cryopreserved cells

via

a one-step method without causing observable damage to cells

superior to the current state-of-the-art cryoprotectants—dimethyl sulfoxide and glycerol. This work provides a new perspective to develop novel cryoprotectants

which may have dramatic impacts on solvent-free cryopreserv

ation technology to support the cell-based applications

such as cell therapy and tissue engineering

etc

.