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 journalArticlepeer-review

29 Citations (Scopus)


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. (Figure presented.).

Original languageEnglish
Pages (from-to)1723-1734
Number of pages12
JournalMacromolecular Bioscience
Issue number11
Publication statusPublished - 2016 Nov 1

Bibliographical note

Funding Information:
R.S. and M.P.H. contributed equally to this work. This work was supported by a National Research Foundation of Korea (NRF) grant (No. 2015R1A2A2A04004469) from the Ministry of Science, ICT and Future Planning, and by Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare (HI16C0133), Republic of Korea.

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


  • ECM stiffness
  • cell differentiation
  • extracellular matrix
  • genipin cross-linking
  • mechanotransduction

ASJC Scopus subject areas

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


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