[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Nanowired three-dimensional cardiac patches

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

Subjects

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.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Leor, J. et al. Bioengineered cardiac grafts: a new approach to repair the infarcted myocardium? Circulation 102, III-56–III-61 (2000).

    Article  CAS  Google Scholar 

  2. Dvir, T. et al. Prevascularization of cardiac patch on the omentum improves its therapeutic outcome. Proc. Natl Acad. Sci. USA 106, 14990–14995 (2009).

    Article  CAS  Google Scholar 

  3. Zimmermann, W. H. et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nature Med. 12, 452–458 (2006).

    Article  CAS  Google Scholar 

  4. Dvir, T., Benishti, N., Shachar, M. & Cohen, S. A novel perfusion bioreactor providing a homogenous milieu for tissue regeneration. Tissue Eng. 12, 2843–2852 (2006).

    Article  CAS  Google Scholar 

  5. Dvir, T., Tsur-Gang, O. & Cohen, S. “Designer” scaffolds for tissue engineering and regeneration. Israel J. Chem. 45, 487–494 (2005).

    Article  CAS  Google Scholar 

  6. Bursac, N., Loo, Y. H., Leong, K. & Tung, L. Novel anisotropic engineered cardiac tissues: studies of electrical propagation. Biochem. Biophys. Res. Commun. 361, 847–853 (2007).

    Article  CAS  Google Scholar 

  7. Radisic, M. et al. Medium perfusion enables engineering of compact and contractile cardiac tissue. Am. J. Physiol. Heart Circ. Physiol. 286, H507–H516 (2004).

    Article  CAS  Google Scholar 

  8. Radisic, M. et al. Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds. Proc. Natl Acad. Sci. USA 101, 18129–18134 (2004).

    Article  CAS  Google Scholar 

  9. Zimmermann, W. H. et al. Tissue engineering of a differentiated cardiac muscle construct. Circ. Res. 90, 223–230 (2002).

    Article  CAS  Google Scholar 

  10. Dvir, T., Levy, O., Shachar, M., Granot, Y. & Cohen, S. Activation of the ERK1/2 cascade via pulsatile interstitial fluid flow promotes cardiac tissue assembly. Tissue Eng. 13, 2185–2193 (2007).

    Article  CAS  Google Scholar 

  11. Engelmayr, G. C. et al. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nature Mater. 7, 1003–1010 (2008).

    Article  CAS  Google Scholar 

  12. Dvir, T., Timko, B. P., Kohane, D. S. & Langer, R. Nanotechnological strategies for engineering complex tissues. Nature Nanotech. 6, 13–22 (2011).

    Article  CAS  Google Scholar 

  13. Sachlos, E., Gotora, D. & Czernuszka, J. T. Collagen scaffolds reinforced with biomimetic composite nano-sized carbonate-substituted hydroxyapatite crystals and shaped by rapid prototyping to contain internal microchannels. Tissue Eng. 12, 2479–2487 (2006).

    Article  CAS  Google Scholar 

  14. Souza, G. R. et al. Three-dimensional tissue culture based on magnetic cell levitation. Nature Nanotech. 5, 291–296 (2010).

    Article  CAS  Google Scholar 

  15. Wu, S. L. et al. A biomimetic hierarchical scaffold: natural growth of nanotitanates on three-dimensional microporous Ti-based metals. Nano Lett. 8, 3803–3808 (2008).

    Article  CAS  Google Scholar 

  16. Timko, B. P. et al. Electrical recording from hearts with flexible nanowire device arrays. Nano Lett. 9, 914–918 (2009).

    Article  CAS  Google Scholar 

  17. Timko, B. P., Cohen-Karni, T., Qing, Q., Tian, B. Z. & Lieber, C. M. Design and implementation of functional nanoelectronic interfaces with biomolecules, cells, and tissue using nanowire device arrays. IEEE Trans. Nanotechnol. 9, 269–280 (2010).

    Article  Google Scholar 

  18. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 830–834.

    Article  CAS  Google Scholar 

  19. Lovat, V. et al. Carbon nanotube substrates boost neuronal electrical signaling. Nano Lett. 5, 1107–1110 (2005).

    Article  CAS  Google Scholar 

  20. Cellot, G. et al. Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts. Nature Nanotech. 4, 126–133 (2009).

    Article  CAS  Google Scholar 

  21. Khlebtsov, N. & Dykman, L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem. Soc. Rev. 40, 1647–1671 (2011).

    Article  CAS  Google Scholar 

  22. Giljohann, D. A. et al. Gold nanoparticles for biology and medicine. Angew. Chem. Int. Ed. 49, 3280–3294 (2010).

    Article  CAS  Google Scholar 

  23. Hao, X. J. et al. Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. Cardiovasc. Res. 75, 178–185 (2007).

    Article  CAS  Google Scholar 

  24. Yu, J. et al. The effect of injected RGD modified alginate on angiogenesis and left ventricular function in a chronic rat infarct model. Biomaterials 30, 751–756 (2009).

    Article  CAS  Google Scholar 

  25. Ruvinov, E., Leor, J. & Cohen, S. The promotion of myocardial repair by the sequential delivery of IGF-1 and HGF from an injectable alginate biomaterial in a model of acute myocardial infarction. Biomaterials 32, 565–578 (2011).

    Article  CAS  Google Scholar 

  26. ClinicalTrials.gov. ID: NCT01226563. IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction.

  27. Gole, A. & Murphy, C. J. Seed-mediated synthesis of gold nanorods: role of the size and nature of the seed. Chem. Mater. 16, 3633–3640 (2004).

    Article  CAS  Google Scholar 

  28. Kim, F., Sohn, K., Wu, J. S. & Huang, J. X. Chemical synthesis of gold nanowires in acidic solutions. J. Am. Chem. Soc. 130, 14442–14443 (2008).

    Article  CAS  Google Scholar 

  29. Mitamura, K., Imae, T., Saito, N. & Takai, O. Fabrication and self-assembly of hydrophobic gold nanorods. J. Phys. Chem. B 111, 8891–8898 (2007).

    Article  CAS  Google Scholar 

  30. Tjong, S. C. Structural and mechanical properties of polymer nanocomposites. Mater. Sci. Eng. R. Rep. 53, 73–197 (2006).

    Article  Google Scholar 

  31. Balazs, A. C., Emrick, T. & Russell, T. P. Nanoparticle polymer composites: where two small worlds meet. Science 314, 1107–1110 (2006).

    Article  CAS  Google Scholar 

  32. Godier-Furnemont, A. F. et al. Composite scaffold provides a cell delivery platform for cardiovascular repair. Proc. Natl Acad. Sci. USA 108, 7974–7979 (2011).

    Article  CAS  Google Scholar 

  33. Horowitz, P. & Hill, W. The Art of Electronics (Cambridge Univ. Press, 1989).

Download references

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.

Author information

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

Authors
  1. Tal Dvir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian P. Timko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark D. Brigham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shreesh R. Naik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sandeep S. Karajanagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Oren Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hongwei Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kevin K. Parker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Robert Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Daniel S. Kohane
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to Daniel S. Kohane.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 899 kb)

Supplementary information

Supplementary movie 1 (AVI 7660 kb)

Supplementary information

Supplementary movie 2 (AVI 5346 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2011.160

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing