Cited by 59Cellular Mechanics and InteractionsTissue Engineering and Regenerative MedicineTGF-β signaling in diseases

Modelling and targeting mechanical forces in organ fibrosis

Open access
Mascharak, Shamik, L. Guo, Jason, Griffin, Michelle, E. Berry, Charlotte, C. Wan, Derrick, T. Longaker, Michael·2024·Nature Reviews Bioengineering

Abstract

Few efficacious therapies exist for the treatment of fibrotic diseases, such as skin scarring, liver cirrhosis and pulmonary fibrosis, which is related to our limited understanding of the fundamental causes and mechanisms of fibrosis. Mechanical forces from cell-matrix interactions, cell-cell contact, fluid flow and other physical stimuli may play a central role in the initiation and propagation of fibrosis. In this Review, we highlight the mechanotransduction mechanisms by which various sources of physical force drive fibrotic disease processes, with an emphasis on central pathways that may be therapeutically targeted to prevent and reverse fibrosis. We then discuss engineered models of mechanotransduction in fibrosis, as well as molecular and biomaterials-based therapeutic approaches for limiting fibrosis and promoting regenerative healing phenotypes in various organs. Finally, we discuss challenges within fibrosis research that remain to be addressed and that may greatly benefit from next-generation bioengineered model systems.

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Authors
Mascharak, S., L. Guo, J., Griffin, M., E. Berry, C., C. Wan, D., & T. Longaker, M.
Affiliations
Stanford Medicine (US)
Venue
Nature Reviews Bioengineering
Published
2024-01-18
Volume
2
Issue
4
Pages
305-323
ISSN
2731-6092 (ISSN-L)
OpenAlex
W4390964997
Cited by
59
References
226
Citations by year
2026: 33 · 2025: 21 · 2024: 5
FWCI
3.12
Type
journal article
Language
en
Open access
Locations
  • Nature Reviews Bioengineering (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (F32HL167318)
  • National Institute of General Medical Sciences (R01GM136659)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR081343)
  • National Institute of Dental and Craniofacial Research (R01DE027346, U24DE029463, R01DE032677)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
organ fibrosis, mechanotransduction, mechanical forces, cell-matrix interactions, cell-cell contact, fluid flow, pulmonary fibrosis, liver cirrhosis, scar tissue

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