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Cytocompatible click-based hydrogels with dynamically tunable properties through orthogonal photoconjugation and photocleavage reactions

Nature Chemistry volume 3, pages 925–931 (2011)Cite this article

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Abstract

To provide insight into how cells receive information from their external surroundings, synthetic hydrogels have emerged as systems for assaying cell function in well-defined microenvironments where single cues can be introduced and subsequent effects individually elucidated. However, as answers to more complex biological questions continue to be sought, advanced material systems are needed that allow dynamic alteration of the three-dimensional cellular environment with orthogonal reactions that enable multiple levels of control of biochemical and biomechanical signals. Here, we seek to synthesize one such three-dimensional culture system using cytocompatible and wavelength-specific photochemical reactions to create hydrogels that allow orthogonal and dynamic control of material properties through independent spatiotemporally regulated photocleavage of crosslinks and photoconjugation of pendant functionalities. The results demonstrate the versatile nature of the chemistry to create programmable niches to study and direct cell function by modifying the local hydrogel environment.

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Figure 1: Synthesis, photocoupling and photodegradation for tuning chemical and physical properties of click-based hydrogels.
Figure 2: Biochemical patterning within preformed click hydrogels using visible light.
Figure 3: Biophysical patterning within pre-formed click hydrogels using ultraviolet light.
Figure 4: Orthogonality of photocoupling and photodegradation reactions.
Figure 5: Culture and recovery of hMSCs from hydrogel microenvironments.
Figure 6: Directed three-dimensional cell motility within patterned hydrogels.

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Acknowledgements

The authors thank A. Kloxin and M. Tibbitt for useful discussions regarding photopatterning, C-C. Lin for advice on cell outgrowth experiments, A. Aimetti and P. Hume for communication on general experimental design, and C. Kloxin for insightful feedback on the written manuscript. Fellowship assistance to C.A.D. was awarded by the US Department of Education's Graduate Assistantships in Areas of National Need. This work was made possible by financial support from the National Science Foundation (DMR 1006711) and the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Chemical and Biological Engineering, University of Colorado, UCB Box 424, Boulder, 80309-0424, Colorado, USA

    Cole A. DeForest & Kristi S. Anseth

  2. Howard Hughes Medical Institute, University of Colorado, UCB Box 424, Boulder, 80309-0424, Colorado, USA

    Kristi S. Anseth

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  1. Cole A. DeForest
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Contributions

C.A.D. and K.S.A. developed the material concept. C.A.D. and K.S.A. designed the experiments. C.A.D. carried out the experiments. C.A.D. and K.S.A. wrote the manuscript.

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Correspondence to Kristi S. Anseth.

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DeForest, C., Anseth, K. Cytocompatible click-based hydrogels with dynamically tunable properties through orthogonal photoconjugation and photocleavage reactions. Nature Chem 3, 925–931 (2011). https://doi.org/10.1038/nchem.1174

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