Injectable dextran hydrogels fabricated by metal-free click chemistry for cartilage tissue engineering.
Injectable dextran-based hydrogels were prepared for the first time by bioorthogonal click chemistry for cartilage tissue engineering. Click-crosslinked injectable hydrogels based on cyto-compatible dextran (Mw=10kDa) were successfully fabricated under physiological conditions by metal-free alkyne-azide cycloaddition (click) reaction between azadibenzocyclooctyne-modified dextran (Dex-ADIBO) and azide-modified dextran (Dex-N3). Gelation time of these dextran hydrogels could be regulated in the range of approximately 1.1 to 10.2min, depending on the polymer concentrations (5% or 10%) and ADIBO substitution degree (DS, 5 or 10) of Dex-ADIBO. Rheological analysis indicated that the dextran hydrogels were elastic and had storage moduli from 2.1 to 6.0kPa with increasing DS of ADIBO from 5 to 10. The in vitro tests revealed that the dextran hydrogel crosslinked from Dex-ADIBO DS 10 and Dex-N3DS 10 at a polymer concentration of 10% could support high viability of individual rabbit chondrocytes and the chondrocyte spheroids encapsulated in the hydrogel over 21days. Individual chondrocytes and chondrocyte spheroids in the hydrogel could produce cartilage matrices such as collagen and glycosaminoglycans. However, the chondrocyte spheroids produced a higher content of matrices than individual chondrocytes. This study indicates that metal-free click chemistry is effective to produce injectable dextran hydrogels for cartilage tissue engineering.
Department of Periodontology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, PR China.
Xiaoyu
X
Wang
The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China.
Zihan
Z
Li
The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China.
Ting
T
Shi
The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China.
Peng
P
Zhao
Department of Periodontology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, PR China. Electronic address: xxstiger@tongji.edu.cn.
Kangkang
K
An
The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China. Electronic address: chaolin@tongji.edu.cn.
Chao
C
Lin
Department of Periodontology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, PR China. Electronic address: hwliu@tongji.edu.cn.
Hongwei
H
Liu
D000818:Animals; D002356:Cartilage / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D057930:Click Chemistry / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003911:Dextrans / Q000138:chemical synthesis / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D007267:Injections; D008670:Metals; D066244:Proton Magnetic Resonance Spectroscopy; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D018874:Spheroids, Cellular / Q000166:cytology; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*
D003432:Cross-Linking Reagents; D003911:Dextrans; D020100:Hydrogels; D008670:Metals
Cell spheroids; Chondrocyte; Click chemistry; Dextran; Metal-free