title: Cytocompatible in situ forming chitosan/hyaluronan hydrogels via a metal-free click chemistry for soft tissue engineering.
abstract: Injectable hydrogels are important cell scaffolding materials for tissue engineering and regenerative medicine. Here, we report a new class of biocompatible and biodegradable polysaccharide hydrogels derived from chitosan and hyaluronan via a metal-free click chemistry, without the addition of copper catalyst. For the metal-free click reaction, chitosan and hyaluronan were modified with oxanorbornadiene (OB) and 11-azido-3,6,9-trioxaundecan-1-amine (AA), respectively. The gelation is attributed to the triazole ring formation between OB and azido groups of polysaccharide derivatives. The molecular structures were verified by FT-IR spectroscopy and elemental analysis, giving substitution degrees of 58% and 47% for chitosan-OB and hyaluronan-AA, respectively. The in vitro gelation, morphologies, equilibrium swelling, compressive modulus and degradation of the composite hydrogels were examined. The potential of the metal-free hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this metal-free hydrogel could support survival and proliferation of ASCs. A preliminary in vivo study demonstrated the usefulness of the hydrogel as an injectable scaffold for adipose tissue engineering. These characteristics provide a potential opportunity to use the metal-free click chemistry in preparation of biocompatible hydrogels for soft tissue engineering applications.
authors.affiliation: School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Mao
authors.affiliation: School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China. Electronic address: hptan@njust.edu.cn.
authors.forename: Huaping
authors.initials: H
authors.lastname: Tan
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D048271:Chitosan / Q000494:pharmacology*; D057930:Click Chemistry / Q000379:methods*; D019245:Compressive Strength / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008422:Materials Testing; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D009636:Norbornanes / Q000737:chemistry; D012212:Rheology / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000187:drug effects; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C000596076:7-oxanorbornadiene; D001672:Biocompatible Materials; D020100:Hydrogels; D009636:Norbornanes; D006820:Hyaluronic Acid; D004247:DNA; D048271:Chitosan
keywords: Adipose-derived stem cells; Chitosan; Hyaluronan; Hydrogel; Tissue engineering