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    Tunable Surface Repellency Maintains Sternness and Redox Capacity of Human Mesenchymal Stem Cells

    Year: 2017

    Journal: ACS Appl. Mater. Interfaces, Volume 9, JUL 12, page 22994–23006

    Authors: Balikov, Daniel A.; Crowder, Spencer W.; Boire, Timothy C.; Lee, Jung Bok; Gupta, Mukesh K.; Fenix, Aidan M.; Lewis, Holley N.; Ambrose, Caitlyn M.; Short, Philip A.; Kim, Chang Soo; Burnette, Dylan T.; Reilly, Matthew A.; Murthy, N. Sanjeeva; Kang, Mi-Lan; kim, Won Shik; Sung, Hak-Joon

    Keywords: polymers; biomaterials; stem cells; regenerative medicine; cell-matrix interface

    Human bone marrow derived mesenchymal stem cells (hMSCs) hold great promise for regenerative medicine due to their multipotent differentiation capacity and immunomodulatory capabilities. Substantial research has elucidated mechanisms by which extracellular cues regulate hMSC fate decisions, but considerably less work has addressed how material properties can be leveraged to maintain undifferentiated stem cells. Here, we show that synthetic culture substrates designed to exhibit moderate cell-repellency promote high sternness and low oxidative stress two indicators of naive, healthy stem cells in commercial and patient-derived hMSCs. Furthermore, the material-mediated effect on cell behavior can be tuned by altering the molar percentage (mol %) and/or chain length of poly(ethylene glycol) (PEG), the repellant block linked to hydrophobic poly(e-caprolactone) (PCL) in the copolymer backbone. Nano- and angstrom-scale characterization of the cell-material interface reveals that PEG interrupts the adhesive PCL domains in a chain-length-dependent manner; this prevents hMSCs from forming mature focal adhesions and subsequently promotes cell cell adhesions that require connexin-43. This study is the first to demonstrate that intrinsic properties of synthetic materials can be tuned to regulate the sternness and redox capacity of hMSCs and provides new insight for designing highly scalable, programmable culture platforms for clinical translation.
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