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Hydrogels with tunable stress relaxation regulate stem cell fate and activity
Ovijit Chaudhuri1,2,3, Luo Gu1,2, Darinka Klumpers1,2,4
1School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature Materials
|December 1, 2015
Summary
Synthetic biomaterials mimicking natural extracellular matrices (ECM) can be engineered for faster stress relaxation. This enhances mesenchymal stem cell (MSC) functions and bone-like matrix formation in 3D cultures.
Area of Science:
- Biomaterials Science
- Cell Biology
- Tissue Engineering
Background:
- Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation.
- Synthetic hydrogels for 3D cell culture are typically elastic, not mimicking natural ECM properties.
- Tuning material properties is crucial for effective cell-material interactions.
Purpose of the Study:
- To develop a materials approach for tuning hydrogel stress relaxation rates independently of other properties.
- To investigate the impact of tunable stress relaxation on mesenchymal stem cell (MSC) behavior.
- To explore the mechanisms underlying cell responses to hydrogel stress relaxation.
Main Methods:
- Fabrication of hydrogels with independently controlled stress relaxation rates.
- 3D culture of MSCs within these tunable hydrogels.
- Assessment of cell spreading, proliferation, and osteogenic differentiation.
- Analysis of underlying molecular and mechanical signaling pathways.
Main Results:
- Hydrogel stress relaxation rate was modulated independently of elastic modulus, degradation, and ligand density.
- Faster stress relaxation significantly enhanced MSC spreading, proliferation, and osteogenic differentiation.
- MSCs in rapidly relaxing hydrogels formed mineralized, collagen-1-rich matrices resembling bone.
- Stress relaxation effects were mediated by ligand binding, actomyosin contractility, and ligand clustering.
Conclusions:
- Stress relaxation is a critical, tunable parameter for biomaterial design in 3D cell culture.
- Engineered viscoelasticity, specifically stress relaxation, can significantly improve cell function and matrix deposition.
- This work provides a new design strategy for biomaterials to better recapitulate native cell-ECM interactions.
