title: Covalently crosslinked chitosan hydrogel formed at neutral pH and body temperature.
abstract: Water-soluble chitosan having double bonds (CS-MA-LA) was synthesized by sequential grafting of methacrylic acid (MA) and lactic acid (LA) via the reaction between amino groups and carboxyl groups under the catalysis of carbodiimide. Its molecular structure was verified by FTIR and (1)H NMR characterizations. Elemental analysis measured grafting ratios of 19% and 10.33% for MA and LA, respectively. CS-MA-LA was readily soluble in pure water and did not precipitate till pH 9. Gelation of the CS-MA-LA was realized by thermal treatment at body temperature under the initiation of a redox system, ammonium persulfate (APS)/N, N,N',N'-tetramethylethylenediamine (TEMED). The gelation time could be mediated in a wide range, e.g. from 6 to 20 min, by reaction temperature and/or initiator's concentration. 3T3 fibroblast culture showed that the cytotoxicity of the hydrogel extractant was dependent on the cell seeding number and the initiator's concentration. With enough number of cells (>2.5 x 10(4)) and low initiator's concentration (5 mM), the cytotoxicity introduced by the initiator is very minimal and negligible. Although the hydrogel could cause acute inflammation and foreign body reaction, no tissue necrosis and malignant infection were evidenced in vivo, demonstrating that the material has better histocompatibility. These features have endowed the chitosan with great opportunity as injectable biomaterials, which may find wide applications in the rapidly developed fields such as tissue engineering and orthopedics.
authors.affiliation: Key Laboratory of Macromolecule Synthesis and Functionalization of the Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Mao
authors.forename: Hualin
authors.initials: H
authors.lastname: Wang
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
authors.forename: Jiacong
authors.initials: J
authors.lastname: Shen
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D048271:Chitosan / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D006358:Hot Temperature; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing / Q000379:methods; D051379:Mice; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan