期刊
ADVANCED FUNCTIONAL MATERIALS
卷 26, 期 21, 页码 3649-3662出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201600092
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资金
- Swiss National Science Foundation [315230_159783, 315230_143667]
- Center for Applied Biotechnology and Molecular Medicine (CABMM)
- FIFA/F-MARC (FIFA Medical Assessment and Research Center)
- Norwegian Research Council [221576]
- National Institutes of Health [NIH R01 HD049808]
- NICHD
- Swiss National Science Foundation (SNF) [315230_143667] Funding Source: Swiss National Science Foundation (SNF)
Deciphering the roles of chemical and physical features of the extracellular matrix (ECM) is vital for developing biomimetic materials with desired cellular responses in regenerative medicine. Here, it is demonstrated that sulfation of biopolymers, mimicking the proteoglycans in native tissues, induces mitogenicity, chondrogenic phenotype, and suppresses catabolic activity of chondrocytes, a cell type that resides in a highly sulfated tissue. Through tunable modification of alginate it is shown that increased sulfation of the microenvironment promotes fibroblast growth factor (FGF) signaling-mediated proliferation of chondrocytes in a 3D matrix independent of stiffness, swelling, and porosity. Furthermore, for the first time it is shown that a biomimetic hydrogel acts as a 3D signaling matrix to mediate a heparan sulfate/heparin-like interaction between FGF and its receptor leading to signaling cascades inducing cell proliferation, cartilage matrix production, and suppression of dedifferentiation markers. Collectively, this study reveals important insights on mimicking the ECM to guide self-renewal of cells via manipulation of distinct signaling mechanisms.
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