Mind the viscous modulus: the mechanotransductive response to the viscous nature of isoelastic matrices regulates stem cell chondrogenesis

Walker, M. , Pringle, E. W., Ciccone, G., Oliver Cervello, L., Tassieri, M. , Gourdon, D. and Cantini, M. (2023) Mind the viscous modulus: the mechanotransductive response to the viscous nature of isoelastic matrices regulates stem cell chondrogenesis. Advanced Healthcare Materials, (doi: 10.1002/adhm.202302571) (PMID:38014647) (Early Online Publication)

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Abstract

The design of hydrogels as mimetics of tissues’ matrices typically disregards the viscous nature of native tissues and focuses only on their elastic properties. In the case of stem cell chondrogenesis, this has led to contradictory results, likely due to unreported changes in the matrices’ viscous modulus. Here, by employing isoelastic matrices with Young's modulus of ≈12 kPa, variations in viscous properties alone (i.e., loss tangent between 0.1 and 0.25) are demonstrated to be sufficient to drive efficient growth factor-free chondrogenesis of human mesenchymal stem cells, both in 2D and 3D cultures. The increase of the viscous component of RGD-functionalized polyacrylamide or polyethylene glycol maleimide hydrogels promotes a phenotype with reduced adhesion, alters mechanosensitive signaling, and boosts cell–cell contacts. In turn, this upregulates the chondrogenic transcription factor SOX9 and supports neocartilage formation, demonstrating that the mechanotransductive response to the viscous nature of the matrix can be harnessed to direct cell fate.

Item Type:Articles
Additional Information:This work was funded by a grant from the UK Regenerative Medicine Platform. MC and DG, respectively, acknowledge MRC funding (MR/S005412/1) and Royal Society of the United Kingdom funding under the Wolfson award (RSWF/FT/191020).
Keywords:Hydrogels, viscoelasticity, stem cells, chondrogenesis, mechanotransduction.
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:CICCONE, Mr GIUSEPPE and Pringle, Eonan and Tassieri, Dr Manlio and Oliver Cervello, Mr Lluís and Walker, Dr Matthew and Cantini, Dr Marco and Gourdon, Professor Delphine
Authors: Walker, M., Pringle, E. W., Ciccone, G., Oliver Cervello, L., Tassieri, M., Gourdon, D., and Cantini, M.
College/School:College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Advanced Healthcare Materials
Publisher:Wiley
ISSN:2198-3844
ISSN (Online):2198-3844
Published Online:28 November 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Advanced Healthcare Materials 2023
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.1545

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303613Engineered microenvironments to harvest stem cell response to viscosity for cartilage repairMarco CantiniMedical Research Council (MRC)MR/S005412/1ENG - Biomedical Engineering
310302Manipulating proteins to engineer 3D platforms for cancer researchDelphine GourdonThe Royal Society (ROYSOC)RSWF/FT/191020ENG - Biomedical Engineering