title: Tunable Crosslinked Cell-Derived Extracellular Matrix Guides Cell Fate.
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.
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 34113, Republic of Korea.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subbiah
authors.affiliation: Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
authors.forename: Mintai P
authors.initials: MP
authors.lastname: Hwang
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 34113, Republic of Korea.
authors.forename: Ping
authors.initials: P
authors.lastname: Du
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 34113, Republic of Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Suhaeri
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Jun-Ha
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 34113, Republic of Korea.
authors.forename: Kwideok
authors.initials: K
authors.lastname: Park
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D060833:Cellular Microenvironment; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D005109:Extracellular Matrix / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D039823:Iridoids / Q000737:chemistry / Q000494:pharmacology; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods
chemical_list: D020099:Coated Materials, Biocompatible; D039823:Iridoids; C007834:genipin
keywords: ECM stiffness; cell differentiation; extracellular matrix; genipin cross-linking; mechanotransduction