@article {601601,
	title = {Hydrogels with tunable stress relaxation regulate stem cell fate and activity},
	journal = {Nat Mater},
	volume = {15},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {326-34},
	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{\textquoteright}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.},
	keywords = {Alginates, Biomechanical Phenomena, Cell Culture Techniques, Cell Differentiation, Extracellular Matrix, Glucuronic Acid, Hexuronic Acids, Humans, Hydrogels, Mesenchymal Stromal Cells, Stress, Mechanical},
	issn = {1476-1122},
	doi = {10.1038/nmat4489},
	author = {Chaudhuri, Ovijit and Gu, Luo and Klumpers, Darinka and Darnell, Max and Bencherif, Sidi A and Weaver, James C and Huebsch, Nathaniel and Lee, Hong-Pyo and Lippens, Evi and Duda, Georg N and Mooney, David J}
}
