ARTICLES NATURE MATERIALS DOl: 10.1038/NMAT3404 8. Hutmacher, D. w. Biomaterials offer cancer research the third dimension. 32. Sapir, Y, Kryukov, O. Cohen, S Integration of multiple cell-matrix ature mater9,9093(2010) nteractions into alginate scaffolds for promoting cardiac tissue regeneration. 9. Huh, D et al. Reconstituting organ-level lung functions on a chip. Science 328, materials32,1838-1847(201 1662-1668(2010) 33. Xu, T. et aL. Electrophysiological characterization of embryonic 3D collagen hydrogel Biomateria 11. Schwille, P Bottom-up synthetic biology: Engineering in a Tinkerer's world 30,4377-4383(2009) cience333,1252-1254(2011) 34. Cho, S.H. et al. Biocompatible SU-8-based microprobes for recording neural 12. Ruder, W. C. Lu, T. Collins, JJ Synthetic biology moving into the clinic. Tence333,12481252(2011) 1830-1836(2008) 13. Timko, B P. et al. Electrical recording from hearts with flexible nanowire 35. Voskerician, G et al. Biocompatibility and biofouling of MEMS drug delivery ys. Nano 14. Viventi, J. et aL. A conformal, bio-interfaced class of silicon electronics for devices biomaterials 24 36. Zipes, D.P. Jalife, J. Cardiac Electrophysiology: From Cell to Bedside 5th edn 15. Kim, D-H. et al. Materials for multifunctional balloon catheters with 37. L'Heureux, N, Paquet, S, Labbe, R, Germain, L.& Auger, F.A.A in cardiac electrophysiological mapping and ablation therapy letely biological tissue-engineered human blood vessel. FASEB J. 12, 16. Viventi, J et al. Flexible, foldable, actively multiplexed, high-density electrode 38. L'Heureux, N et al. Human tissue-engineered blood vessels for adult arterial 17. Kim, D-H et al. Epidermal electronics cine ae resci 14, 1599-1605(2011) revascularization. Nature Med. 12, 361-365(2006) 39. Neri, D. Supuran, C.T. Interfering with pH regulation in tumours as a 18. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as calized bioprobe 329,831-834(2010) 40. Kraut, J.A. Madias, N. E Metabolic acidosis: pathophysiology, diagnosis Qing, Q. et al. Nanowire transisto neural circuits in acute and management. Nature Rev. Nephrol. 6, 274-285(2010) brain slices. Proc. Natl Acad. Sci. US.A 107, 1882-1887(2010) 41. Dvir, T et al. Nanowired three-dimensional cardiac patches. Nature Nanotech. 6,720-725(2011). recording from cells using nanowire transistor arrays. Proc Natl Acad. Sci. USA 42. Sekitani, T et al. A rubberlike stretchable active matrix using elastic conductors. 106,7309-7313(2009) Science321,1468-1472(2008) 21. Timko, B P, Cohen-Karni, T, Qing, Q, Tian, B. Lieber, C. M. Design and 43. Mannsfeld, S C. B. et al Highly sensitive flexible pressure sensors lementation of functional nanoelectronic interfaces with biomolecules ith micro-structured rubber as the dielectric layer. Nature Mater. 9, ells, and tissue using nanowire device arrays. IEEE Trans. Nanotech. 9, 859864(2010 269-280(2010) 44. Takei, K et al. Nanowire active matrix circuitry for low-voltage macro-scale 2. Prohaska, O J, Olcaytug, F, Pfundner, P. Dragaun, H. Thin-film multiple artificial skin. Nature Mater. 9, 821-826(2010) electrode probes: Possibilities and limitations. IEEE Trans. Biomed Eng 223-229(1986) 23 Nicolelis, M.A. L(ed) Methods for Neural Ensemble Recordings 2nd edn(CRC, Acknowledgements We thank F Kosar for help on uCr imaging of synthetic tissue samples and 4. McKnight, T. E. et al. Resident neuroelectrochemical inter facing using carbon for assistance with culture chamber preparation C.M.L. acknowledges supp nanofibre arrays. Phys. Chem. B 110, 15317-15327(2006) 25. Yu, Z. et al. Vertically aligned carbon nanofibre arrays record Neurosciences Award. D.S. K acknowledg electrophysiological signals from hippocampal slices. Nano Lett. 7, GM073626.RS L acknowledges NIH grants DED13023 and DE016516. 26. Dequach, J A, Yuan, S.H. Goldstein, L S. Christman, K L Decellularized brain matrix for cell culture and tissue engineering scaffolds. Tissu Author contributions EngA17,2583-2592(2011) B.T. J.L. T D, D.S.K. and C.M. L designed the ex ts B.T.and J. L perfo Hanley, P. J, Young, A. A, LeGrice, I. J, Edgar, S.G.& Loiselle, D S. Thre experiments. T.D. ]. T and Q.Q. assisted in the ini of the project. L J. and Z.S. dimensional configuration of perimysial collagen fibres in rat cardiac muscle performed calculations and simulations. B T, J.L. and C.M.L. wrote the paper. All ngths. Physio.517,831-837(1999 28. Engelmayr, G.C. -like honeycombs for tissue engineering of authors discussed the results and commented on the manuscript. cardiac anisotropy Nature Mater. 7, 1003-1010(2008) Additional information 841-850(2007) of the paper. Reprints and 30.Yan,h.etal.Programmablenanowirecircuitsfornanoprocessor.Nature470.permissionsinformationisavailableonlineatwww.nature.com/reprints.correspondence 240-2442011) and requests for materials should be addressed to D.S. K or C.M. 31. Wang, M. F, Maleki, T. Ziaie, B. Enhanced silicon microstructures via thermal shrinkage of a composite organic/inorganic Competing financial interests bilayer. IEEE/ASME J. Microelectromech. Syst. 17, 882-889(2008) The authors declare no competing financial interests. NATURE MATERIALS I VOL 11 I NOVEMBER 2012 I G 2012 Macmillan Publishers Limited All rights reservedARTICLES NATURE MATERIALS DOI:10.1038/NMAT3404 8. Hutmacher, D. W. Biomaterials offer cancer research the third dimension. Nature Mater. 9, 90–93 (2010). 9. Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010). 10. Baker, M. Tissue models: A living system on a chip. Nature 471, 661–665 (2011). 11. Schwille, P. Bottom-up synthetic biology: Engineering in a Tinkerer’s world. Science 333, 1252–1254 (2011). 12. Ruder, W. C., Lu, T. & Collins, J. J. Synthetic biology moving into the clinic. Science 333, 1248–1252 (2011). 13. Timko, B. P. et al. Electrical recording from hearts with flexible nanowire device arrays. Nano Lett. 9, 914–918 (2009). 14. Viventi, J. et al. A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology. Sci. Transl. Med. 2, 24ra22 (2010). 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). 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). 17. Kim, D-H. et al. Epidermal electronics. Science 333, 838–843 (2011). 18. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 831–834 (2010). 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). 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). 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). 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). 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). 25. Yu, Z. et al. Vertically aligned carbon nanofibre arrays record electrophysiological signals from hippocampal slices. Nano Lett. 7, 2188–2195 (2007). 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). 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). 28. Engelmayr, G. C. Jr et al. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nature Mater. 7, 1003–1010 (2008). 29. Lu, W. & Lieber, C. M. Nanoelectronics from the bottom up. Nature Mater. 6, 841–850 (2007). 30. Yan, H. et al. Programmable nanowire circuits for nanoprocessor. Nature 470, 240–244 (2011). 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). 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). 33. Xu, T. et al. Electrophysiological characterization of embryonic hippocampal neurons cultured in a 3D collagen hydrogel. Biomaterials 30, 4377–4383 (2009). 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). 35. Voskerician, G. et al. Biocompatibility and biofouling of MEMS drug delivery devices. Biomaterials 24, 1959–1967 (2003). 36. Zipes, D. P. & Jalife, J. Cardiac Electrophysiology: From Cell to Bedside 5th edn (Saunders, 2009). 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). 38. L’Heureux, N. et al. Human tissue-engineered blood vessels for adult arterial revascularization. Nature Med. 12, 361–365 (2006). 39. Neri, D. & Supuran, C. T. Interfering with pH regulation in tumours as a therapeutic strategy. Nature Rev. Drug Discov. 10, 767–777 (2011). 40. Kraut, J. A. & Madias, N. E. Metabolic acidosis: pathophysiology, diagnosis and management. Nature Rev. Nephrol. 6, 274–285 (2010). 41. Dvir, T. et al. Nanowired three-dimensional cardiac patches. Nature Nanotech. 6, 720–725 (2011). 42. Sekitani, T.et al. A rubberlike stretchable active matrix using elastic conductors. Science 321, 1468–1472 (2008). 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). 44. Takei, K. et al. Nanowire active matrix circuitry for low-voltage macro-scale artificial skin. Nature Mater. 9, 821–826 (2010). 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. Author 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. Additional information Supplementary information is available in the online version of the paper. Reprints and permissions information is available online atwww.nature.com/reprints. Correspondence and requests for materials should be addressed to D.S.K. or C.M.L. Competing financial interests The authors declare no competing financial interests. 994 NATURE MATERIALS | VOL 11 | NOVEMBER 2012 | www.nature.com/naturematerials © 2012 Macmillan Publishers Limited. All rights reserved