Journal
NATURE MATERIALS
Volume 15, Issue 3, Pages 326-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT4489
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Funding
- NIH [R01 DE013033, CA153802]
- Einstein Visiting Fellowship
- Einstein Foundation Berlin through the Charite Universitatsmedizin Berlin
- Berlin-Brandenburg School for Regenerative Therapies [GSC 203]
- ZonMW-VICI grant (The Netherlands) [918.11.635]
- Harvard MRSEC [DMR-1420570]
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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.
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