title: Fabrication of injectable high strength hydrogel based on 4-arm star PEG for cartilage tissue engineering.
abstract: Hydrogels prepared from poly(ethylene glycol) (PEG) are widely applied in tissue engineering, especially those derived from a combination of functional multi-arm star PEG and linear crosslinker, with an expectation to form a structurally ideal network. However, the poor mechanical strength still renders their further applications. Here we examined the relationship between the dynamics of the pre-gel solution and the mechanical property of the resultant hydrogel in a system consisting of 4-arm star PEG functionalized with vinyl sulfone and short dithiol crosslinker. A method to prepare mechanically strong hydrogel for cartilage tissue engineering is proposed. It is found that when gelation takes place at the overlap concentration, at which a slow relaxation mode just appears in dynamic light scattering (DLS), the resultant hydrogel has a local maximum compressive strength ∼20 MPa, while still keeps ultralow mass concentration and Young's modulus. Chondrocyte-laden hydrogel constructed under this condition was transplanted into the subcutaneous pocket and an osteochondral defect model in SCID mice. The in vivo results show that chondrocytes can proliferate and maintain their phenotypes in the hydrogel, with the production of abundant extracellular matrix (ECM) components, formation of typical chondrocyte lacunae structure and increase in Young's modulus over 12 weeks, as indicated by histological, immunohistochemistry, gene expression analyses and mechanical test. Moreover, newly formed hyaline cartilage was observed to be integrated with the host articular cartilage tissue in the defects injected with chondrocytes/hydrogel constructs. The results suggest that this hydrogel is a promising candidate scaffold for cartilage tissue engineering.
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Hong Kong SAR, PR China. Electronic address: agathis.wang@gmail.com.
authors.forename: Jianqi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China; School of Biomedical Sciences Core Laboratory, Institute of Stem Cell, Genomics and Translational Research, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, PR China.
authors.forename: Fengjie
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China; School of Biomedical Sciences Core Laboratory, Institute of Stem Cell, Genomics and Translational Research, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, PR China.
authors.forename: Wing Pui
authors.initials: WP
authors.lastname: Tsang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China; School of Biomedical Sciences Core Laboratory, Institute of Stem Cell, Genomics and Translational Research, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, PR China. Electronic address: cwan@cuhk.edu.hk.
authors.forename: Chao
authors.initials: C
authors.lastname: Wan
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Hong Kong SAR, PR China; Hefei National Laboratory for Physical Sciences at Microsacle, Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, PR China.
authors.forename: Chi
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology* / Q000254:growth & development*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D020219:Chondrogenesis / Q000502:physiology; D019245:Compressive Strength; D055119:Elastic Modulus; D006244:Hardness; D020100:Hydrogels / Q000008:administration & dosage / Q000138:chemical synthesis*; D007267:Injections; D008297:Male; D008422:Materials Testing; D051379:Mice; D016513:Mice, SCID; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis*; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014783:Viscosity
chemical_list: D020100:Hydrogels; D011092:Polyethylene Glycols
keywords: Cartilage tissue engineering; Chondrocyte; Injectable hydrogel; Overlap concentration; Star PEG; Young's modulus