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.

New directions and dimensions for bioengineered models of fibrosis

Nature Reviews Materials volume 6, pages 192–195 (2021)Cite this article

Subjects

During fibrotic diseases, functional tissue parenchyma progressively transforms into stiff, disorganized and non-functional tissue causing organ failure. The underlying multitude of interconnected changes in the cellular microenvironment can be investigated using bioengineered fibrosis models.

Fibrosis is the process of dysregulated wound healing and is often associated with numerous lethal conditions including cancer, cardiac disease and respiratory failure. Despite its ubiquity in disease, a thorough pathophysiological understanding of fibrosis remains elusive owing to the diversity and complexity of this process in vivo. In vitro culture models have helped elucidate the role of microenvironmental cues and signalling pathways that contribute to the differentiation of myofibroblasts — a cell type that directly drives fibrogenesis. However, recent single-cell transcriptomic studies have raised questions about the identities and signalling pathways of cells contributing to fibrosis1. Bioengineered disease models offer the opportunity to address outstanding questions in the biology and treatment of fibrosis.

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

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Fig. 1: Dissecting the dynamics of fibrosis.

References

  1. Habermann, A. C. et al. Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci. Adv. 6, eaba1972 (2020).

    Article  CAS  Google Scholar 

  2. Fiore, V. F. et al. αvβ3 Integrin drives fibroblast contraction and strain stiffening of soft provisional matrix during progressive fibrosis. JCI insight https://doi.org/10.1172/jci.insight.97597 (2018).

    Article  Google Scholar 

  3. Rosales, A. M. & Anseth, K. S. The design of reversible hydrogels to capture extracellular matrix dynamics. Nat. Rev. Mater. 1, 15012 (2016).

    Article  CAS  Google Scholar 

  4. Pakshir, P. et al. Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix. Nat. Commun. 10, 1850 (2019).

    Article  Google Scholar 

  5. Loebel, C., Mauck, R. L. & Burdick, J. A. Local nascent protein deposition and remodelling guide mesenchymal stromal cell mechanosensing and fate in three-dimensional hydrogels. Nat. Mater. 18, 883–891 (2019).

    Article  CAS  Google Scholar 

  6. Ham, T. R., Collins, K. L. & Hoffman, B. D. Molecular tension sensors: moving beyond force. Curr. Opin. Biomed. Eng. 12, 83–94 (2019).

    Article  Google Scholar 

  7. Matera, D. L. et al. Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in myofibroblast differentiation. Sci. Adv. 6, eabb5069 (2020).

    Article  CAS  Google Scholar 

  8. Trappmann, B. et al. Matrix degradability controls multicellularity of 3D cell migration. Nat. Commun. 8, 1–8 (2017).

    Article  CAS  Google Scholar 

  9. Cao, Z. et al. Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis. Sci. Transl. Med. 9, eaai8710 (2017).

    Article  Google Scholar 

  10. Lovisa, S. et al. Endothelial-to-mesenchymal transition compromises vascular integrity to induce Myc-mediated metabolic reprogramming in kidney fibrosis. Sci. Signal. 13, eabb8834 (2020).

    Article  Google Scholar 

Download references

Acknowledgements

W.Y.W. and D.L.M. acknowledge financial support from the National Science Foundation Graduate Research Fellowship Program (DGE1256260). B.M.B. acknowledges financial support from an NIH Pathway to Independence Award (HL124322) and the University of Michigan MCubed Program.

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

    Daniel L. Matera & Brendon M. Baker

  2. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA

    William Y. Wang & Brendon M. Baker

Authors
  1. Daniel L. Matera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brendon M. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the preparation of the manuscript.

Corresponding author

Correspondence to Brendon M. Baker.

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

Matera, D.L., Wang, W.Y. & Baker, B.M. New directions and dimensions for bioengineered models of fibrosis. Nat Rev Mater 6, 192–195 (2021). https://doi.org/10.1038/s41578-021-00288-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41578-021-00288-x

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research