Tunable Crosslinked Cell-Derived Extracellular Matrix Guides Cell Fate

Ramesh Subbiah, Mintai P. Hwang, Ping Du, Muhammad Suhaeri, Jun Ha Hwang, Jeong-Ho Hong, Kwideok Park

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Extracellular matrix (ECM), comprised of multiple cues (chemical, physiomechanical), provides a niche for cell attachment, migration, and differentiation. Given that different cells give rise to distinct physiological milieus, the role of such microenvironmental cues on various cells has been well-studied. Particularly, the effect of various physiomechanical factors on stem cell lineage has been resolved into individual variables via ECM protein-coated polymeric systems. Such platforms, while providing a reductionist approach as a means to remove any confounding factors, unfortunately fall short of capturing the full biophysical scope of the natural microenvironment. Herein, the use of a cell-derived ECM platform is reported in which its crosslinking density is tunable; varying concentrations (0, 0.5, 1, 2% w/v) of genipin (GN), a naturally derived crosslinker with low toxicity, are used to form inter- and intrafibril crosslinks. ECM crosslinking produces GN concentration-dependent changes in ECM stiffness (<0.1-9.4 kPa), roughness (96-280 nm), and chemical composition (100-60% amine content). The effect of the various crosslinked ECM profiles on human mesenchymal stem cell differentiation, vascular morphogenesis, and cardiomyogenesis are then evaluated. Taken together, this study demonstrates that tunable crosslinked cell-derived ECM platform is capable of providing a comprehensive physiological platform, and envisions its use in future tissue engineering applications.

Original languageEnglish
JournalMacromolecular Bioscience
DOIs
Publication statusAccepted/In press - 2016

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Keywords

  • Cell differentiation
  • ECM stiffness
  • Extracellular matrix
  • Genipin cross-linking
  • Mechanotransduction

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Subbiah, R., Hwang, M. P., Du, P., Suhaeri, M., Hwang, J. H., Hong, J-H., & Park, K. (Accepted/In press). Tunable Crosslinked Cell-Derived Extracellular Matrix Guides Cell Fate. Macromolecular Bioscience. https://doi.org/10.1002/mabi.201600280