A Temperature/Sorbitol-Responsive Dissociable Hydrogel for In Vitro Stem Cell Proliferation and Harvest

Three-dimensional (3D) cell culture using hydrogels offers superb methods to expand cells and study signaling molecules modulating cell behaviors in vitro . However, it is still a great challenge to establish a degradable nonfouling platform for mimicking and simplifying the extracellular matrix (ECM) for cell proliferation and harvest. In this work, a dissociable hydrogel (mXSP) was fabricated, which included the thermosensitive galactose-modified xyloglucan (mXG) network and the zwitterionic network cross-linked by d -sorbitol-responsive phenylboronic ester bonds. The zwitterionic polymers provide hydrogels with an ultralow-fouling property as a nonfouling platform. The temperature/ d -sorbitol dual-sensitive networks of the mXSP hydrogels made them easier to dissociate. The mechanical and nonfouling properties, gelation, and degradable behavior of mXSP hydrogels were investigated in detail. Lastly, the efficacy of the mXSP hydrogels for cell expansion and harvest was evaluated. It was demonstrated that the mXSP hydrogels had tunable stiffness and could support robust cell proliferation continuously. Furthermore, expanded cells could be harvested from the mXSP hydrogel with high viability and harvest ratio by adding the biocompatible d -sorbitol solution and adjusting the temperature. To sum up, the cell supporting and releasing mXSP hydrogels as a nonfouling platform provided in this work showed great promise for 3D cell expansion and harvest in vitro .