Sulfated Hydrogel Matrices Direct Mitogenicity and Maintenance of Chondrocyte Phenotype through Activation of FGF Signaling

Ece Öztürk, Øystein Arlov, Seda Aksel, Li Ling, David M. Ornitz, Gudmund Skjåk-Bræk, Marcy Zenobi-Wong

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3649-3662
Number of pages14
JournalAdvanced Functional Materials
Volume26
Issue number21
DOIs
StatePublished - Jun 7 2016

Keywords

  • biomedical applications
  • biomimetics
  • hydrogels
  • tissue engineering

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