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Nanowired three-dimensional cardiac patches

Nature Nanotechnology volume 6, pages 720–725 (2011)Cite this article

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Abstract

Engineered cardiac patches for treating damaged heart tissues after a heart attack are normally produced by seeding heart cells within three-dimensional porous biomaterial scaffolds1,2,3. These biomaterials, which are usually made of either biological polymers such as alginate4 or synthetic polymers such as poly(lactic acid) (PLA)5, help cells organize into functioning tissues, but poor conductivity of these materials limits the ability of the patch to contract strongly as a unit6. Here, we show that incorporating gold nanowires within alginate scaffolds can bridge the electrically resistant pore walls of alginate and improve electrical communication between adjacent cardiac cells. Tissues grown on these composite matrices were thicker and better aligned than those grown on pristine alginate and when electrically stimulated, the cells in these tissues contracted synchronously. Furthermore, higher levels of the proteins involved in muscle contraction and electrical coupling are detected in the composite matrices. It is expected that the integration of conducting nanowires within three-dimensional scaffolds may improve the therapeutic value of current cardiac patches.

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Figure 1: Schematic overview of three-dimensional nanowire cardiac tissue.
Figure 2: Incorporation of nanowires within alginate scaffolds.
Figure 3: Increased electrical conductivity of alginate by incorporation of nanowires.
Figure 4: Cardiac cell organization within the three-dimensional scaffold.
Figure 5: Calcium transient propagation within engineered tissues.

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Acknowledgements

This research was funded by the National Institutes of Health (NIH, grants GM073626 to D.S.K. and DE13023 and DE016516 to R.L.). T.D. thanks the American Heart Association for a Postdoctoral Fellowship. B.P.T. acknowledges an NIH Ruth L. Kirschstein National Research Service Award (no. F32GM096546). The authors would like to thank H. Park, B. Tian, D. Liu, A. Argun and L. Bellan for their assistance and discussions.

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Author notes

  1. Tal Dvir and Brian P. Timko: These authors contributed equally to this work

Authors and Affiliations

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

    Tal Dvir, Brian P. Timko, Shreesh R. Naik, Sandeep S. Karajanagi & Robert Langer

  2. Department of Anesthesiology, Division of Critical Care Medicine, Laboratory for Biomaterials and Drug Delivery, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Tal Dvir, Brian P. Timko & Daniel S. Kohane

  3. Disease Biophysics Group, Wyss Institute for Biologically-Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, 02138, Massachusetts, USA

    Mark D. Brigham, Hongwei Jin & Kevin K. Parker

  4. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Sandeep S. Karajanagi

  5. Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, 02139, Massachusetts, USA

    Oren Levy

  6. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, 02139, Massachusetts, USA

    Oren Levy

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Contributions

T.D. and B.P.T. conceived the idea. T.D., B.P.T., K.K.P., R.L. and D.S.K. designed the experiments and interpreted the data. T.D., B.P.T., M.D.B., S.R.N., S.S.K. and O.L. performed the experiments. H.J. analysed data. T.D., B.P.T. and D.S.K. co-wrote the paper.

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Correspondence to Daniel S. Kohane.

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The authors declare no competing financial interests.

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Dvir, T., Timko, B., Brigham, M. et al. Nanowired three-dimensional cardiac patches. Nature Nanotech 6, 720–725 (2011). https://doi.org/10.1038/nnano.2011.160

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