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Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells

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Abstract

Identification of biomaterials that support appropriate cellular attachment, proliferation and gene expression patterns is critical for tissue engineering and cell therapy. Here we describe an approach for rapid, nanoliter-scale synthesis of biomaterials and characterization of their interactions with cells. We simultaneously characterize over 1,700 human embryonic stem cell–material interactions and identify a host of unexpected materials effects that offer new levels of control over human embryonic stem cell behavior.

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Figure 1: Biomaterial microarray design.
Figure 2: hES cells grown on polymer arrays.
Figure 3: 'Hit' polymer effects on hES cell attachment, growth and proliferation.
Figure 4: hES cells grown on 'hit' arrays.

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Acknowledgements

The authors would like to thank David Putnam, David Lynn, David Lavan and Daniel Kohane for helpful advice, Mara Macdonald for help with cell culture and Joseph Itskovitz-Eldor for assistance and cooperation in conducting this research. We would also like to thank Sean Milton and the BioMicro Center for help with slide analysis. This work was supported by the National Science Foundation (through the MIT Biotechnology Process and Engineering Center) and the National Institutes of Health (grant no. HL60435).

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Authors and Affiliations

  1. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Daniel G Anderson, Shulamit Levenberg & Robert Langer

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  1. Daniel G Anderson
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  2. Shulamit Levenberg
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  3. Robert Langer
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Correspondence to Robert Langer.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

C2C12 cells grown on polymer arrays. (PDF 104 kb)

Supplementary Fig. 2

Design of “hit” Polymer arrays (PDF 214 kb)

Supplementary Fig. 3

Standard deviation of Cell coverage on Different Materials (PDF 118 kb)

Supplementary Fig. 4

Cells per spot with RA, on day one (PDF 82 kb)

Supplementary Fig. 5

Cells per spot with RA, on day six (PDF 81 kb)

Supplementary Table 1

Percent cells cytokeratin 7 positive on different materials over time (PDF 26 kb)

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Anderson, D., Levenberg, S. & Langer, R. Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotechnol 22, 863–866 (2004). https://doi.org/10.1038/nbt981

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