title: Injectable Polypeptide Hydrogels with Tunable Microenvironment for 3D Spreading and Chondrogenic Differentiation of Bone-Marrow-Derived Mesenchymal Stem Cells.
abstract: Bone-marrow-derived mesenchymal stem cells (BMSCs) possess vast potential for tissue engineering and regenerative medicine. In this study, an injectable hydrogel comprising poly(l-glutamic acid)-graft-tyramine (PLG-g-TA) with tunable microenvironment was developed via enzyme-catalyzed cross-linking and used as an artificial extracellular matrix (ECM) to explore the behaviors of BMSCs during three-dimensional (3D) culture. It was found that the mechanical property, porous structure as well as degradation process of the hydrogels could be tuned by changing the copolymer concentration. The PLG-g-TA hydrogels showed good cytocompatibility in vitro. After being subcutaneously injected into the back of rats, the hydrogels degraded gradually within 8 weeks and exhibited good biocompatibility in vivo. BMSCs were then encapsulated in the polypeptide-based hydrogels with different copolymer concentration to investigate the influence of 3D matrix microenvironment on stem cell behaviors. It is intriguing to note that the BMSCs within the 2% hydrogel showed a well-spread morphology after 24 h and a higher proliferation rate during 7 days of culture, in contrast to a rounded morphology and lower proliferation rate of BMSCs in the 4% hydrogel. Furthermore, the hydrogels with different microenvironment also regulated the matrix biosynthesis and the gene expression of BMSCs. After incubation in the 2% hydrogel for 4 weeks, the BMSCs produced more type II collagen and expressed higher amounts of chondrogenic markers, compared to the cells in the 4% hydrogel. Therefore, the PLG-g-TA hydrogels with tunable microenvironment may serve as an efficient 3D platform for guiding the lineage specification of BMSCs.
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.|University of Chinese Academy of Sciences , Beijing 100039, P. R. China.
authors: Kaixuan
authors: K
authors: Ren
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.|University of Chinese Academy of Sciences , Beijing 100039, P. R. China.
authors: Haitao
authors: H
authors: Cui
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.|University of Chinese Academy of Sciences , Beijing 100039, P. R. China.
authors: Qinghua
authors: Q
authors: Xu
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors: Chaoliang
authors: C
authors: He
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors: Gao
authors: G
authors: Li
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors: Xuesi
authors: X
authors: Chen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001853:Bone Marrow / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D044968:Regenerative Medicine; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D010455:Peptides