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Hydrogel scaffolds to study cell biology in four dimensions

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Abstract

Poly(ethylene glycol) (PEG) hydrogels represent a versatile material scaffold for culturing cells in two or three dimensions with the advantages of limited protein fouling and cytocompatible polymerization to enable cell encapsulation. By using light-based chemistries for gelation and for incorporating biomolecules into the network, dynamic niches can be created that facilitate the study of how cells respond to user-dictated or cell-dictated changes in environmental signals. Specifically, we demonstrate integration of a photo-cleavable molecule into network cross-links and into pendant functional groups to construct gels with biophysical and biochemical properties that are spatiotemporally tunable with light. Complementary to this approach, an enzymatically cleavable peptide sequence can be introduced within hydrogel networks, in this case through photoinitiated addition reactions between thiol-containing biomacromolecules and ene-containing synthetic polymers, to enable cellular remodeling of their surrounding hydrogel microenvironment. With such tunable material platforms, researchers can employ a systematic approach for 3D cell culture experiments, spatially and temporally modulating physical properties (e.g., stiffness) as well as biological signals (e.g., adhesive ligands) to study cell behavior in response to environmental stimuli. Collectively, these material systems suggest routes for new experimentation to study and manipulate cellular functions in four dimensions.

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Acknowledgements

K.L. would like to thank Ryan Lewis and Mark Tibbitt for helpful discussions while drafting the manuscript. The authors would like to acknowledge funding from the Howard Hughes Medical Institute and NSF (DMR 1006711).

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Authors and Affiliations

  1. University of Colorado at Boulder, USA

    Katherine J. R. Lewis & Kristi S. Anseth

Authors
  1. Katherine J. R. Lewis
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  2. Kristi S. Anseth
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Correspondence to Katherine J. R. Lewis.

Additional information

This article is based on the Mid-Career Researcher Award lecture, presented by Kristi S. Anseth on April 11, 2012, at the 2012 Materials Research Society Spring Meeting in San Francisco. Anseth is recognized for “exceptional achievement at the interface of materials and biology enabling new, functional biomaterials that answer fundamental questions in biology and yield advances in regenerative medicine, stem-cell differentiation, and cancer treatment.”

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Lewis, K.J.R., Anseth, K.S. Hydrogel scaffolds to study cell biology in four dimensions. MRS Bulletin 38, 260–268 (2013). https://doi.org/10.1557/mrs.2013.54

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