Engineering Reversible Hydrogels for 3D Cell Culture and Release Using Diselenide Catalyzed Fast Disulfide Formation

Yueying Han, Cheng Liu, Huaping Xu,* and Yi Cao*

Chin. J. Chem.; 2022, 40, 1578.

Hydrogels crosslinked by dynamic covalent bonds can effectively mimic the viscoelastic properties of native extracellular matrix and have been widely explored for 3D cell culture. Disulfide is one of the most common dynamic bonds in biological systems whose for-mation and cleavage are catalyzed by a set of dedicated enzymes. However, in vitroformation of disulfide bonds is a slow process and requires harsh catalysts. Therefore, it is difficult to use disulfide crosslinked hydrogels for cell culture. In thiswork, we show that disul-fide bonds can be formed by thiol-diselenide (DiSe) exchange under blue light illumination. This reaction is fast, reversible, and bio-compatible. Moreover, residual diselenide in the hydrogel network can also accelerate thioldisulfide exchange reactions leading to faster cell release from the hydrogels upon the addition of thiol-containing agents. We anticipate that disulfide crosslinked hydrogels catalyzed by diselenide can find broad biomedical applications, such as cell culture,cell delivery, and drug-controlled release.