Letter | Published:

Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery

Nature Materials volume 16, pages 236243 (2017) | Download Citation

Abstract

Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel’s mechanical properties1. Here, we report a microfluidic-based method for encapsulating single cells in an approximately six-micrometre layer of alginate that increases the proportion of cell-containing microgels by a factor of ten, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that, for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.

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Acknowledgements

This work was supported by the National Institutes of Health (NIH) Grants RO1EB014703 (D.J.M. and D.A.W.) and K99HL125884 (J.-W.S.), and the National Science Foundation (NSF) Graduate Research Fellowship Program (A.S.M.). S.U. was supported by the Deutsche Forschungsgemeinschaft (DFG).

Author information

Author notes

    • Angelo S. Mao
    •  & Jae-Won Shin

    These authors contributed equally to this work.

Affiliations

  1. Wyss Institute for Biologically Inspired Engineering at Harvard University, Cambridge, Massachusetts 02138, USA

    • Angelo S. Mao
    • , Jae-Won Shin
    • , Oktay Uzun
    • , Weiwei Li
    • , David A. Weitz
    •  & David J. Mooney
  2. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA

    • Angelo S. Mao
    • , Jae-Won Shin
    • , Stefanie Utech
    • , Huanan Wang
    • , Oktay Uzun
    • , Weiwei Li
    • , Madeline Cooper
    • , Yuebi Hu
    • , Liyuan Zhang
    • , David A. Weitz
    •  & David J. Mooney
  3. Department of Pharmacology and Department of Bioengineering, University of Illinois College of Medicine, Chicago, Illinois 60612, USA

    • Jae-Won Shin
  4. Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA

    • Huanan Wang
    • , Liyuan Zhang
    •  & David A. Weitz
  5. Biomaterials and Tissue Engineering Laboratory, School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China

    • Huanan Wang

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Contributions

A.S.M., J.-W.S. and D.J.M. conceived and designed the experiments. S.U., H.W. and D.A.W. contributed to microfluidic design and fabrication. A.S.M. and J.-W.S. performed the experiments. A.S.M., J.-W.S. and D.J.M. analysed the data. A.S.M., J.-W.S. and D.J.M. wrote the manuscript. All authors discussed the results and commented on the manuscript. A.S.M. and J.-W.S. contributed equally to this work. The principal investigator is D.J.M.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David J. Mooney.

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DOI

https://doi.org/10.1038/nmat4781

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