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Micropatterned Biphasic Nanocomposite Platform for Maintaining Chondrocyte Morphology

  • Ram Saraswat
    Ram Saraswat
    Nanoscience and Nanoengineering, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
    More by Ram Saraswat
  • Ishara Ratnayake
    Ishara Ratnayake
    Nanoscience and Nanoengineering, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
  • E. Celeste Perez
    E. Celeste Perez
    Nanoscience and Nanoengineering, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
  • William M. Schutz
    William M. Schutz
    Nanoscience and Nanoengineering, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
  • Zhengtao Zhu
    Zhengtao Zhu
    Nanoscience and Nanoengineering, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
    Chemistry and Applied Biological Sciences, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
    More by Zhengtao Zhu
  • S. Phillip Ahrenkiel
    S. Phillip Ahrenkiel
    Nanoscience and Nanoengineering, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
  • , and 
  • Scott T. Wood*
    Scott T. Wood
    Nanoscience and Nanoengineering, South Dakota School of Mines & Technology, 501 E St Joseph St, Rapid City, South Dakota 57701, United States
    *Email: [email protected]. Tel: +1-605-394-5222.
Cite this: ACS Appl. Mater. Interfaces 2020, 12, 13, 14814–14824
Publication Date (Web):March 23, 2020
https://doi.org/10.1021/acsami.9b22596
Copyright © 2020 American Chemical Society

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    Abstract

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    One major limitation hindering the translation of in vitro osteoarthritis research into clinical disease-modifying therapies is that chondrocytes rapidly spread and dedifferentiate under standard monolayer conditions. Current strategies to maintain rounded morphologies of chondrocytes in culture either unnaturally restrict adhesion and place chondrocytes in an excessively stiff mechanical environment or are impractical for use in many applications. To address the limitations of current techniques, we have developed a unique composite thin-film cell culture platform, the CellWell, to model articular cartilage that utilizes micropatterned hemispheroidal wells, precisely sized to fit individual cells (12–18 μm diameters), to promote physiologically spheroidal chondrocyte morphologies while maintaining compatibility with standard cell culture and analytical techniques. CellWells were constructed of 15-μm-thick 5% agarose films embedded with electrospun poly(vinyl alcohol) (PVA) nanofibers. Transmission electron microscope (TEM) images of PVA nanofibers revealed a mean diameter of 60.9 ± 24 nm, closely matching the observed 53.8 ± 29 nm mean diameter of human ankle collagen II fibers. Using AFM nanoindentation, CellWells were found to have compressive moduli of 158 ± 0.60 kPa at 15 μm/s indentation, closely matching published stiffness values of the native pericellular matrix. Primary human articular chondrocytes taken from ankle cartilage were seeded in CellWells and assessed at 24 h. Chondrocytes maintained their rounded morphology in CellWells (mean aspect ratio of 0.87 ± 0.1 vs three-dimensional (3D) control [0.86 ± 0.1]) more effectively than those seeded under standard conditions (0.65 ± 0.3), with average viability of >85%. The CellWell’s design, with open, hemispheroidal wells in a thin film substrate of physiological stiffness, combines the practical advantages of two-dimensional (2D) culture systems with the physiological advantages of 3D systems. Through its ease of use and ability to maintain the physiological morphology of chondrocytes, we expect that the CellWell will enhance the clinical translatability of future studies conducted using this culture platform.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsami.9b22596.

    • Quantitative analysis of actin fibers from in situ chondrocytes in a murine hip explant (mouse) (Figure S1); distribution of chondrocyte XY area on the different platforms from n = 3 donors (Figure S2); compressive stiffness of agarose at different thicknesses (Table S1) (PDF)

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    This article is cited by 8 publications.

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