Highly Efficient Self-Healable and Dual Responsive Cellulose-Based Hydrogels for Controlled Release and 3D Cell Culture

To face the increasing demand of self-healing hydrogels with biocompatibility and high performances, a new class of cellulose-based self-healing hydrogels are constructed through dynamic covalent acylhydrazone linkages. The carboxyethyl cellulose-graft-dithiodipropionate dihydrazide and dibenzaldehyde-terminated poly(ethylene glycol) are synthesized, and then the hydrogels are formed from their mixed solutions under 4-amino-DL-phenylalanine (4a-Phe) catalysis. The chemical structure, as well as microscopic morphologies, gelation times, mechanical and self-healing performances of the hydrogels are investigated with H-1 NMR, Fourier transform infrared spectroscopy, atomic force microscopy, rheological and compression measurements. Their gelation times can be controlled by varying the total polymer concentration or 4a-Phe content. The resulted hydrogels exhibit excellent self-healing ability with a high healing efficiency (approximate to 96%) and good mechanical properties. Moreover, the hydrogels display pH/redox dual responsive sol-gel transition behaviors, and are applied successfully to the controlled release of doxorubicin. Importantly, benefitting from the excellent biocompatibility and the reversibly cross-linked networks, the hydrogels can function as suitable 3D culture scaffolds for L929 cells, leading to the encapsulated cells maintaining a high viability and proliferative capacity. Therefore, the cellulose-based self-healing hydrogels show potential applications in drug delivery and 3D cell culture for tissue engineering.