The design of reversible hydrogels to capture extracellular matrix dynamics

Abstract

The extracellular matrix (ECM) is a dynamic environment that constantly provides physical and chemical cues to embedded cells. Much progress has been made in engineering hydrogels that can mimic the ECM, but hydrogel properties are, in general, static. To recapitulate the dynamic nature of the ECM, many reversible chemistries have been incorporated into hydrogels to regulate cell spreading, biochemical ligand presentation and matrix mechanics. For example, emerging trends include the use of molecular photoswitches or biomolecule hybridization to control polymer chain conformation, thereby enabling the modulation of the hydrogel between two states on demand. In addition, many non-covalent, dynamic chemical bonds have found increasing use as hydrogel crosslinkers or tethers for cell signalling molecules. These reversible chemistries will provide greater temporal control of adhered cell behaviour, and they allow for more advanced in vitro models and tissue-engineering scaffolds to direct cell fate.

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Figure 1: Biological extracellular matrix and synthetic strategies involving reversible chemistries.
Figure 2: Irreversible and reversible chemistries for hydrogels.
Figure 3: Light-based strategies for exchangeable ligand presentation.
Figure 4: Non-covalent strategies for exchangeable ligand presentation.
Figure 5: Crosslinking effects on bulk hydrogel properties.
Figure 6: Covalent adaptable networks.
Figure 7: Reversible control of matrix mechanics.

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Acknowledgements

K.S.A. acknowledges support from the Howard Hughes Medical Institute and grants from the National Science Foundation (DMR 1408955) and the National Institutes of Health (R01 DE016523). A.M.R. gratefully acknowledges a postdoctoral fellowship from the National Heart, Lung, and Blood Institute of the US National Institutes of Health (Award Number F32HL121986) and a Postdoctoral Enrichment Program Award from the Burroughs Wellcome Fund.

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Rosales, A., Anseth, K. The design of reversible hydrogels to capture extracellular matrix dynamics. Nat Rev Mater 1, 15012 (2016). https://doi.org/10.1038/natrevmats.2015.12

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