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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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 stemness and low oxidative stress - two indicators of naïve, 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(ϵ-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 stemness and redox capacity of hMSCs and provides new insight for designing highly scalable, programmable culture platforms for clinical translation.

Original languageAmerican English
Pages (from-to)22994-23006
Number of pages13
JournalACS Applied Materials and Interfaces
Volume9
Issue number27
DOIs
StatePublished - Jul 12 2017

ASJC Scopus subject areas

  • General Materials Science

Keywords

  • biomaterials
  • cell-matrix interface
  • polymers
  • regenerative medicine
  • stem cells

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