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Highly Efficient Self‐Healable and Dual Responsive Cellulose‐Based Hydrogels for Controlled Release and 3D Cell Culture
Authors:Xuefeng Yang  Guoqiang Liu  Liao Peng  Jinhua Guo  Lei Tao  Jinying Yuan  Chunyu Chang  Yen Wei  Lina Zhang
Affiliation:1. College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, P. R. China;2. The Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, P. R. China;3. School of Chemistry and Chemical Engineering, Guangxi University, Nanning, P. R. China
Abstract: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 1H 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 (≈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.
Keywords:3D cell culture  cellulose‐based hydrogels  dual responsive hydrogels  dynamic acylhydrazone bonds  self‐healing
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