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Macroporous nanowire nanoelectronic scaffolds for synthetic tissues

Nature Materials volume 11, pages 986–994 (2012)Cite this article

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Abstract

The development of three-dimensional (3D) synthetic biomaterials as structural and bioactive scaffolds is central to fields ranging from cellular biophysics to regenerative medicine. As of yet, these scaffolds cannot electrically probe the physicochemical and biological microenvironments throughout their 3D and macroporous interior, although this capability could have a marked impact in both electronics and biomaterials. Here, we address this challenge using macroporous, flexible and free-standing nanowire nanoelectronic scaffolds (nanoES), and their hybrids with synthetic or natural biomaterials. 3D macroporous nanoES mimic the structure of natural tissue scaffolds, and they were formed by self-organization of coplanar reticular networks with built-in strain and by manipulation of 2D mesh matrices. NanoES exhibited robust electronic properties and have been used alone or combined with other biomaterials as biocompatible extracellular scaffolds for 3D culture of neurons, cardiomyocytes and smooth muscle cells. Furthermore, we show the integrated sensory capability of the nanoES by real-time monitoring of the local electrical activity within 3D nanoES/cardiomyocyte constructs, the response of 3D-nanoES-based neural and cardiac tissue models to drugs, and distinct pH changes inside and outside tubular vascular smooth muscle constructs.

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Figure 1: Integrating nanoelectronics with cells and tissue.
Figure 2: Macroporous and flexible nanowire nanoES.
Figure 3: Geometry control by design in nanoES.
Figure 4: Hybrid macroporous nanoelectronic scaffolds.
Figure 5: 3D cell culture and electrical sensing in nanoES.
Figure 6: Synthetic vascular construct enabled for sensing.

References

  1. Na, K. et al. Directing zeolite structures into hierarchically nanoporous architectures. Science 333, 328–332 (2011).

    Article  CAS  Google Scholar 

  2. Schaedler, T. A. et al. Ultralight metallic microlattices. Science 334, 962–965 (2011).

    Article  CAS  Google Scholar 

  3. Place, E. S., George, J. H., Williams, C. K. & Stevens, M. M. Synthetic polymer scaffolds for tissue engineering. Chem. Soc. Rev. 38, 1139–1151 (2009).

    Article  CAS  Google Scholar 

  4. Wylie, R. G. et al. Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. Nature Mater. 10, 799–806 (2011).

    Article  CAS  Google Scholar 

  5. Kloxin, A. M., Kasko, A. M., Salinas, C. N. & Anseth, K. S. Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324, 59–63 (2009).

    Article  CAS  Google Scholar 

  6. 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 

  7. Kraehenbuehl, T. P., Langer, R. & Ferreira, L. Three-dimensional biomaterials for the study of human pluripotent stem cells. Nature Methods 8, 731–736 (2011).

    Article  CAS  Google Scholar 

  8. Hutmacher, D. W. Biomaterials offer cancer research the third dimension. Nature Mater. 9, 90–93 (2010).

    Article  CAS  Google Scholar 

  9. Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010).

    Article  CAS  Google Scholar 

  10. Baker, M. Tissue models: A living system on a chip. Nature 471, 661–665 (2011).

    Article  CAS  Google Scholar 

  11. Schwille, P. Bottom-up synthetic biology: Engineering in a Tinkerer’s world. Science 333, 1252–1254 (2011).

    Article  CAS  Google Scholar 

  12. Ruder, W. C., Lu, T. & Collins, J. J. Synthetic biology moving into the clinic. Science 333, 1248–1252 (2011).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Viventi, J. et al. A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology. Sci. Transl. Med. 2, 24ra22 (2010).

    Article  Google Scholar 

  15. Kim, D-H. et al. Materials for multifunctional balloon catheters with capabilities in cardiac electrophysiological mapping and ablation therapy. Nature Mater. 10, 316–323 (2011).

    Article  CAS  Google Scholar 

  16. Viventi, J. et al. Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo. Nature Neurosci. 14, 1599–1605 (2011).

    Article  CAS  Google Scholar 

  17. Kim, D-H. et al. Epidermal electronics. Science 333, 838–843 (2011).

    Article  CAS  Google Scholar 

  18. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 831–834 (2010).

    Article  Google Scholar 

  19. Qing, Q. et al. Nanowire transistor arrays for mapping neural circuits in acute brain slices. Proc. Natl Acad. Sci. USA 107, 1882–1887 (2010).

    Article  CAS  Google Scholar 

  20. Cohen-Karni, T., Timko, B. P., Weiss, L. E. & Lieber, C. M. Flexible electrical recording from cells using nanowire transistor arrays. Proc. Natl Acad. Sci. USA 106, 7309–7313 (2009).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  22. Prohaska, O. J., Olcaytug, F., Pfundner, P. & Dragaun, H. Thin-film multiple electrode probes: Possibilities and limitations. IEEE Trans. Biomed Eng. 33, 223–229 (1986).

    Article  CAS  Google Scholar 

  23. Nicolelis, M. A. L. (ed.) Methods for Neural Ensemble Recordings 2nd edn (CRC, 2008).

  24. McKnight, T. E. et al. Resident neuroelectrochemical interfacing using carbon nanofibre arrays. J. Phys. Chem. B 110, 15317–15327 (2006).

    Article  CAS  Google Scholar 

  25. Yu, Z. et al. Vertically aligned carbon nanofibre arrays record electrophysiological signals from hippocampal slices. Nano Lett. 7, 2188–2195 (2007).

    Article  CAS  Google Scholar 

  26. Dequach, J. A., Yuan, S. H., Goldstein, L. S. & Christman, K. L. Decellularized porcine brain matrix for cell culture and tissue engineering scaffolds. Tissue Eng. A 17, 2583–2592 (2011).

    Article  CAS  Google Scholar 

  27. Hanley, P. J., Young, A. A., LeGrice, I. J., Edgar, S. G. & Loiselle, D. S. Three dimensional configuration of perimysial collagen fibres in rat cardiac muscle at resting and extended sarcomere lengths. J. Physiol. 517, 831–837 (1999).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Lu, W. & Lieber, C. M. Nanoelectronics from the bottom up. Nature Mater. 6, 841–850 (2007).

    Article  CAS  Google Scholar 

  30. Yan, H. et al. Programmable nanowire circuits for nanoprocessor. Nature 470, 240–244 (2011).

    Article  CAS  Google Scholar 

  31. Wang, M. F., Maleki, T. & Ziaie, B. Enhanced three-dimensional folding of silicon microstructures via thermal shrinkage of a composite organic/inorganic bilayer. IEEE/ASME J. Microelectromech. Syst. 17, 882–889 (2008).

    Article  CAS  Google Scholar 

  32. Sapir, Y., Kryukov, O. & Cohen, S. Integration of multiple cell-matrix interactions into alginate scaffolds for promoting cardiac tissue regeneration. Biomaterials 32, 1838–1847 (2011).

    Article  CAS  Google Scholar 

  33. Xu, T. et al. Electrophysiological characterization of embryonic hippocampal neurons cultured in a 3D collagen hydrogel. Biomaterials 30, 4377–4383 (2009).

    Article  CAS  Google Scholar 

  34. Cho, S. H. et al. Biocompatible SU-8-based microprobes for recording neural spike signals from regenerated peripheral nerve fibres. IEEE Sensors J. 8, 1830–1836 (2008).

    Article  Google Scholar 

  35. Voskerician, G. et al. Biocompatibility and biofouling of MEMS drug delivery devices. Biomaterials 24, 1959–1967 (2003).

    Article  CAS  Google Scholar 

  36. Zipes, D. P. & Jalife, J. Cardiac Electrophysiology: From Cell to Bedside 5th edn (Saunders, 2009).

    Google Scholar 

  37. L’Heureux, N., Pâquet, S., Labbé, R., Germain, L. & Auger, F. A. A completely biological tissue-engineered human blood vessel. FASEB J. 12, 47–56 (1998).

    Article  Google Scholar 

  38. L’Heureux, N. et al. Human tissue-engineered blood vessels for adult arterial revascularization. Nature Med. 12, 361–365 (2006).

    Article  Google Scholar 

  39. Neri, D. & Supuran, C. T. Interfering with pH regulation in tumours as a therapeutic strategy. Nature Rev. Drug Discov. 10, 767–777 (2011).

    Article  CAS  Google Scholar 

  40. Kraut, J. A. & Madias, N. E. Metabolic acidosis: pathophysiology, diagnosis and management. Nature Rev. Nephrol. 6, 274–285 (2010).

    Article  CAS  Google Scholar 

  41. Dvir, T. et al. Nanowired three-dimensional cardiac patches. Nature Nanotech. 6, 720–725 (2011).

    Article  CAS  Google Scholar 

  42. Sekitani, T. et al. A rubberlike stretchable active matrix using elastic conductors. Science 321, 1468–1472 (2008).

    Article  CAS  Google Scholar 

  43. Mannsfeld, S. C. B. et al. Highly sensitive flexible pressure sensors with micro-structured rubber as the dielectric layer. Nature Mater. 9, 859–864 (2010).

    Article  CAS  Google Scholar 

  44. Takei, K. et al. Nanowire active matrix circuitry for low-voltage macro-scale artificial skin. Nature Mater. 9, 821–826 (2010).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank F. Kosar for help on μCT imaging of synthetic tissue samples and J. L. Huang for assistance with culture chamber preparation. C.M.L. acknowledges support from a NIH Director’s Pioneer Award and a McKnight Foundation Technological Innovations in Neurosciences Award. D.S.K. acknowledges a Biotechnology Research Endowment from the Department of Anesthesiology at Children’s Hospital Boston and NIH grant GM073626. R.S.L. acknowledges NIH grants DE013023 and DE016516.

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Author notes

  1. Bozhi Tian, Jia Liu and Tal Dvir: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    Bozhi Tian, Jia Liu, Quan Qing & Charles M. Lieber

  2. Department of Anesthesiology, Division of Critical Care Medicine, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA

    Bozhi Tian, Tal Dvir, Jonathan H. Tsui & Daniel S. Kohane

  3. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    Bozhi Tian & Robert Langer

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

    Tal Dvir & Robert Langer

  5. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA

    Lihua Jin, Zhigang Suo & Charles M. Lieber

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  1. Bozhi Tian
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Contributions

B.T., J.L., T.D., D.S.K. and C.M.L. designed the experiments. B.T. and J.L. performed experiments. T.D., J.T. and Q.Q. assisted in the initial stage of the project. L.J. and Z.S. performed calculations and simulations. B.T., J.L., D.S.K. and C.M.L. wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Daniel S. Kohane or Charles M. Lieber.

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The authors declare no competing financial interests.

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Tian, B., Liu, J., Dvir, T. et al. Macroporous nanowire nanoelectronic scaffolds for synthetic tissues. Nature Mater 11, 986–994 (2012). https://doi.org/10.1038/nmat3404

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