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Nat Mater. 2016 Mar;15(3):326-34. doi: 10.1038/nmat4489. Epub 2015 Nov 30.

Hydrogels with tunable stress relaxation regulate stem cell fate and activity.

Author information

1
School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
2
Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
3
Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA.
4
Department of Orthopedic Surgery, Research Institute MOVE, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
5
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA.
6
Julius Wolff Institute, Charité-Universitätsmedizin Berlin and Berlin-Brandenburg Center for Regenerative Therapies, 13353 Berlin, Germany.

Abstract

Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel's initial elastic modulus, degradation, and cell-adhesion-ligand density. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.

PMID:
26618884
PMCID:
PMC4767627
DOI:
10.1038/nmat4489
[Indexed for MEDLINE]
Free PMC Article
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