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.

Harnessing the secreted extracellular matrix to engineer tissues

As an intermediary between cells and scaffolding biomaterials, the extracellular matrix secreted by the cells offers challenges and opportunities for the design and fabrication of engineered tissues.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Biomaterials inspired by the extracellular matrix and cell-mediated material remodelling.
Fig. 2: Biomaterial-based strategies for harnessing the secreted ECM.
Fig. 3: Applications of the cell-secreted matrix.

References

  1. 1.

    Sharma, B. et al. Sci. Transl. Med. 5, 167ra166 (2013).

    Google Scholar 

  2. 2.

    Occhetta, P. et al. Nat. Biomed. Eng. 3, 545–557 (2019).

    CAS  PubMed  Google Scholar 

  3. 3.

    Nguyen, E. H. et al. Nat. Biomed. Eng. 1, 0096 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Ferreira, S. A. et al. Nat. Commun. 9, 4049 (2018).

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Loebel, C., Mauck, R. L. & Burdick, J. A. Nat. Mater. 18, 883–891 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Blache, U. et al. EMBO Rep. 19, e45964 (2018).

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Vining, K. H. & Mooney, D. J. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Butcher, D. T., Alliston, T. & Weaver, V. M. Nat. Rev. Cancer 9, 108–122 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Evans, N. D. & Gentleman, E. J. Mater. Chem. B 2, 2345–2356 (2014).

    CAS  PubMed  Google Scholar 

  10. 10.

    Huleihel, L. et al. Sci. Adv. 2, e1600502 (2016).

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Madl, C. M. et al. Nat. Mater. 16, 1233–1242 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Chaudhuri, O. et al. Nat. Mater. 15, 326–334 (2016).

    CAS  PubMed  Google Scholar 

  13. 13.

    Huebsch, N. et al. Nat. Mater. 9, 518–526 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Khetan, S. et al. Nat. Mater. 12, 458–465 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Ranga, A. et al. Proc. Natl Acad. Sci. USA 113, 6831–6839 (2016).

    Google Scholar 

  16. 16.

    Enemchukwu, N. O. et al. J. Cell. Biol. 212, 113–124 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Gjorevski, N. et al. Nature 539, 560–564 (2016).

    CAS  PubMed  Google Scholar 

  18. 18.

    Cruz-Acuna, R. et al. Nat. Cell Biol. 19, 1326–1335 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Bonnans, C., Chou, J. & Werb, Z. Nat. Rev. Mol. Cell Biol. 15, 786–801 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Bissell, M. J., Hall, H. G. & Parry, G. J. Theor. Biol. 99, 31–68 (1982).

    CAS  PubMed  Google Scholar 

  21. 21.

    Morgner, J. et al. Nat. Commun. 6, 8198 (2015).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Roskelley, C. D. & Bissell, M. J. Biochem. Cell Biol. 73, 391–397 (1995).

    CAS  PubMed  Google Scholar 

  23. 23.

    Kloxin, A. M., Kasko, A. M., Salinas, C. N. & Anseth, K. S. Science 324, 59–63 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Lutolf, M. P. et al. Proc. Natl Acad. Sci. USA 100, 5413–5418 (2003).

    CAS  PubMed  Google Scholar 

  25. 25.

    Rosales, A. M. & Anseth, K. S. Nat. Rev. Mater. 1, 15012 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Scott, K. E., Rychel, K., Ranamukhaarachchi, S., Rangamani, P. & Fraley, S. I. Acta Biomater. 96, 81–98 (2019).

    CAS  PubMed  Google Scholar 

  27. 27.

    Hudalla, G. A., Eng, T. S. & Murphy, W. L. Biomacromolecules 9, 842–849 (2008).

    CAS  PubMed  Google Scholar 

  28. 28.

    Devaud, Y. R. et al. Adv. Healthc. Mater. 7, 1800534 (2018).

    Google Scholar 

  29. 29.

    Murad, S. et al. Proc. Natl Acad. Sci. USA 78, 2879–2882 (1981).

    CAS  PubMed  Google Scholar 

  30. 30.

    Spence, J. R. et al. Nature 470, 105–109 (2011).

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Capeling, M. M. et al. Stem Cell Rep. 12, 381–394 (2019).

    CAS  Google Scholar 

  32. 32.

    Arora, N. et al. Development 144, 1128–1136 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Shadish, J. A., Benuska, G. M. & DeForest, C. A. Nat. Mater. 18, 1005–1014 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Metzger, S. et al. Macromol. Biosci. 16, 1703–1713 (2016).

    CAS  PubMed  Google Scholar 

  35. 35.

    Chen, X. D., Dusevich, V., Feng, J. Q., Manolagas, S. C. & Jilka, R. L. J. Bone Miner. Res. 22, 1943–1956 (2007).

    CAS  PubMed  Google Scholar 

  36. 36.

    Yamaguchi, Y., Mann, D. M. & Ruoslahti, E. Nature 346, 281–284 (1990).

    CAS  PubMed  Google Scholar 

  37. 37.

    Hezaveh, H. et al. Biomacromolecules 19, 721–730 (2018).

    CAS  PubMed  Google Scholar 

  38. 38.

    Lee, T. T. et al. Nat. Mater. 14, 352–360 (2015).

    CAS  PubMed  Google Scholar 

  39. 39.

    Stejskalova, A., Oliva, N., England, F. J. & Almquist, B. D. Adv. Mater. 31, 1806380 (2019).

    Google Scholar 

  40. 40.

    Fridy, P. C. et al. Nat. Methods 11, 1253–1260 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Kamperman, T. et al. Adv. Healthc. Mater. 6, 1600913 (2017).

    Google Scholar 

  42. 42.

    Bryant, S. J. & Anseth, K. S. J. Biomed. Mater. Res. A 64, 70–79 (2003).

    Google Scholar 

  43. 43.

    Bryant, S. J. & Anseth, K. S. J. Biomed. Mater. Res. 59, 63–72 (2002).

    CAS  PubMed  Google Scholar 

  44. 44.

    Benoit, D. S., Schwartz, M. P., Durney, A. R. & Anseth, K. S. Nat. Mater. 7, 816–823 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Dupont, S. et al. Nature 474, 179–183 (2011).

    CAS  PubMed  Google Scholar 

  46. 46.

    Mao, A. S. et al. Nat. Mater. 16, 236–243 (2017).

    CAS  PubMed  Google Scholar 

  47. 47.

    Rozario, T. & DeSimone, D. W. Dev. Biol. 341, 126–140 (2010).

    CAS  PubMed  Google Scholar 

  48. 48.

    Hautanen, A., Gailit, J., Mann, D. M. & Ruoslahti, E. J. Biol. Chem. 264, 1437–1442 (1989).

    CAS  PubMed  Google Scholar 

  49. 49.

    Quarta, M. et al. Nat. Biotechnol. 34, 752–759 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Baghdadi, M. B. et al. Nature 557, 714–718 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Millman, J. R. & Pagliuca, F. W. Diabetes 66, 1111–1120 (2017).

    CAS  PubMed  Google Scholar 

  52. 52.

    Mamidi, A. et al. Nature 564, 114–118 (2018).

    CAS  PubMed  Google Scholar 

  53. 53.

    Bochenek, M. A. et al. Nat. Biomed. Eng. 2, 810–821 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Nat. Biomed. Eng. 2, 879–880 (2018).

  55. 55.

    Shin, J. W. & Mooney, D. J. Proc. Natl Acad. Sci. USA 113, 12126–12131 (2016).

    CAS  PubMed  Google Scholar 

  56. 56.

    McLeod, C. M. & Mauck, R. L. Sci. Rep. 6, 38852 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Mayorca-Guiliani, A. E. et al. Nat. Med. 23, 890–898 (2017).

    CAS  PubMed  Google Scholar 

  58. 58.

    Costa-Silva, B. et al. Nat. Cell Biol. 17, 816–826 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Oskarsson, T. et al. Nat. Med. 17, 867–874 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Carpenter, R. A., Kwak, J. G., Peyton, S. R. & Lee, J. Nat. Biomed. Eng. 2, 915–929 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Parker, M. W. et al. J. Clin. Invest. 124, 1622–1635 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Li, C. X. et al. Nat. Mater. 16, 379–389 (2017).

    CAS  PubMed  Google Scholar 

  63. 63.

    Horejs, C. M. et al. Nat. Commun. 8, 15509 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Ferreira, S. A. et al. Biomaterials 176, 13–23 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

U.B. acknowledges postdoctoral-funding support from the Balgrist University Hospital Zurich. M.M.S and E.G. acknowledge support from the UK Regenerative Medicine Platform ‘Acellular / Smart Materials – 3D Architecture’ (grant no. MR/R015651/1).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Molly M. Stevens or Eileen Gentleman.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Blache, U., Stevens, M.M. & Gentleman, E. Harnessing the secreted extracellular matrix to engineer tissues. Nat Biomed Eng 4, 357–363 (2020). https://doi.org/10.1038/s41551-019-0500-6

Download citation

Further reading

Search

Quick links