Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Multi-responsive hydrogel structures from patterned droplet networks

Nature Chemistry volume 12, pages 363–371 (2020)Cite this article

Subjects

Abstract

Responsive hydrogels that undergo controlled shape changes in response to a range of stimuli are of interest for microscale soft robotic and biomedical devices. However, these applications require fabrication methods capable of preparing complex, heterogeneous materials. Here we report a new approach for making patterned, multi-material and multi-responsive hydrogels, on a micrometre to millimetre scale. Nanolitre aqueous pre-gel droplets were connected through lipid bilayers in predetermined architectures and photopolymerized to yield continuous hydrogel structures. By using this droplet network technology to pattern domains containing temperature-responsive or non-responsive hydrogels, structures that undergo reversible curling were produced. Through patterning of gold nanoparticle-containing domains into the hydrogels, light-activated shape change was achieved, while domains bearing magnetic particles allowed movement of the structures in a magnetic field. To highlight our technique, we generated a multi-responsive hydrogel that, at one temperature, could be moved through a constriction under a magnetic field and, at a second temperature, could grip and transport a cargo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Multi-responsive hydrogel structures templated by droplet networks.
Fig. 2: Formation and temperature response of PNIPAm hydrogel structures templated with droplet networks.
Fig. 3: Patterned fluorescent PNIPAm hydrogel structures.
Fig. 4: Shape changes of structures containing two different temperature-responsive hydrogels.
Fig. 5: Shape changes of structures containing light-responsive domains.
Fig. 6: A magnetically and dual temperature-responsive shape-changing structure.
Fig. 7: Cargo transport and maze navigation by a magnetically responsive and dual temperature-responsive hydrogel gripper.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

The MATLAB code used for image analysis in this study is available from the corresponding author upon reasonable request.

References

  1. Li, T. et al. Fast-moving soft electronic fish. Sci. Adv. 3, e1602045 (2017).

    Article  Google Scholar 

  2. Huang, H. W., Sakar, M. S., Petruska, A. J., Pané, S. & Nelson, B. J. Soft micromachines with programmable motility and morphology. Nat. Commun. 7, 12263 (2016).

    Article  CAS  Google Scholar 

  3. Hu, W., Lum, G. Z., Mastrangeli, M. & Sitti, M. Small-scale soft-bodied robot with multimodal locomotion. Nature 554, 81–85 (2018).

    Article  CAS  Google Scholar 

  4. Zhou, Y., Hauser, A. W., Bende, N. P., Kuzyk, M. G. & Hayward, R. C. Waveguiding microactuators based on a photothermally responsive nanocomposite hydrogel. Adv. Funct. Mater. 26, 5447–5452 (2016).

    Article  CAS  Google Scholar 

  5. Leong, T. G. et al. Tetherless thermobiochemically actuated microgrippers. Proc. Natl Acad. Sci. USA 106, 703–708 (2009).

    Article  CAS  Google Scholar 

  6. Fernandes, R. & Gracias, D. H. Self-folding polymeric containers for encapsulation and delivery of drugs. Adv. Drug Deliv. Rev. 64, 1579–1589 (2012).

    Article  CAS  Google Scholar 

  7. Rus, D. & Tolley, M. T. Design, fabrication and control of soft robots. Nature 521, 467–475 (2015).

    Article  CAS  Google Scholar 

  8. Breger, J. C. et al. Self-folding thermo-magnetically responsive soft microgrippers. ACS Appl. Mater. Interfaces 7, 3398–3405 (2015).

    Article  CAS  Google Scholar 

  9. Ionov, L. Biomimetic hydrogel-based actuating systems. Adv. Funct. Mater. 23, 4555–4570 (2013).

    Article  CAS  Google Scholar 

  10. Schild, H. G. Poly(N-isopropylacrylamide): experiment, theory and application. Prog. Polym. Sci. 17, 163–249 (1992).

    Article  CAS  Google Scholar 

  11. Hoffman, A. S. Stimuli-responsive polymers: biomedical applications and challenges for clinical translation. Adv. Drug Deliv. Rev. 65, 10–16 (2013).

    Article  CAS  Google Scholar 

  12. Hashmi, B. et al. Developmentally-inspired shrink-wrap polymers for mechanical induction of tissue differentiation. Adv. Mater. 26, 3253–3257 (2014).

    Article  CAS  Google Scholar 

  13. Kim, H. et al. Visible light-triggered on-demand drug release from hybrid hydrogels and its application in transdermal patches. Adv. Healthcare Mater. 4, 2071–2077 (2015).

    Article  CAS  Google Scholar 

  14. Kim, J., Hanna, J. A., Byun, M., Santangelo, C. D. & Hayward, R. C. Designing responsive buckled surfaces by halftone gel lithography. Science 335, 1201–1205 (2012).

    Article  CAS  Google Scholar 

  15. Gladman, A. S., Matsumoto, E. A., Nuzzo, R. G., Mahadevan, L. & Lewis, J. A. Biomimetic 4D printing. Nat. Mater. 15, 413–418 (2016).

    Article  Google Scholar 

  16. Cangialosi, A. et al. DNA sequence-directed shape change of photopatterned hydrogels via high-degree swelling. Science 357, 1126–1130 (2017).

    Article  CAS  Google Scholar 

  17. Zhang, Y. S. & Khademhosseini, A. Advances in engineering hydrogels. Science 356, eaaf3627 (2017).

    Article  Google Scholar 

  18. Booth, M. J., Restrepo Schild, V., Downs, F. G. & Bayley, H. Functional aqueous droplet networks. Mol. Biosyst. 13, 1658–1691 (2017).

    Article  CAS  Google Scholar 

  19. Graham, A. D. et al. High-resolution patterned cellular constructs by droplet-based 3D printing. Sci. Rep. 7, 7004 (2017).

    Article  Google Scholar 

  20. Sapra, K. T. & Bayley, H. Lipid-coated hydrogel shapes as components of electrical circuits and mechanical devices. Sci. Rep. 2, 848 (2012).

    Article  Google Scholar 

  21. Booth, M. J., Schild, V. R., Graham, A. D., Olof, S. N. & Bayley, H. Light-activated communication in synthetic tissues. Sci. Adv. 2, e1600056 (2016).

    Article  Google Scholar 

  22. Booth, M. J., Restrepo Schild, V., Box, S. J. & Bayley, H. Light-patterning of synthetic tissues with single droplet resolution. Sci. Rep. 7, 9315 (2017).

    Article  Google Scholar 

  23. Holden, M. A., Needham, D. & Bayley, H. Functional bionetworks from nanoliter water droplets. J. Am. Chem. Soc. 129, 8650–8655 (2007).

    Article  CAS  Google Scholar 

  24. Maglia, G. et al. Droplet networks with incorporated protein diodes show collective properties. Nat. Nanotechnol. 4, 437–440 (2009).

    Article  CAS  Google Scholar 

  25. Villar, G., Graham, A. D. & Bayley, H. A tissue-like printed material. Science 340, 48–52 (2013).

    Article  CAS  Google Scholar 

  26. Villar, G., Heron, A. J. & Bayley, H. Formation of droplet networks that function in aqueous environments. Nat. Nanotechnol. 6, 803–808 (2011).

    Article  CAS  Google Scholar 

  27. Wauer, T. et al. Construction and manipulation of functional three-dimensional droplet networks. ACS Nano 8, 771–779 (2014).

    Article  CAS  Google Scholar 

  28. Kim, S., Lee, K. & Cha, C. Refined control of thermoresponsive swelling/deswelling and drug release properties of poly(N-isopropylacrylamide) hydrogels using hydrophilic polymer crosslinkers. J. Biomater. Sci. Polym. Ed. 27, 1698–1711 (2016).

    Article  CAS  Google Scholar 

  29. Hauser, A. W., Evans, A. A., Na, J. H. & Hayward, R. C. Photothermally reprogrammable buckling of nanocomposite gel sheets. Angew. Chem. Int. Ed. 54, 5434–5437 (2015).

    Article  CAS  Google Scholar 

  30. Sutton, A. et al. Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell manipulation. Nat. Commun. 8, 14700 (2017).

    Article  Google Scholar 

  31. Shibayama, M. & Tanaka, T. in Responsive Gels: Volume Transitions I. Advances in Polymer Science Vol. 109 (ed. Dušek, K.) 1–62 (Springer, 1993).

  32. Elani, Y., Demello, A. J., Niu, X. & Ces, O. Novel technologies for the formation of 2-D and 3-D droplet interface bilayer networks. Lab Chip 12, 3514–3520 (2012).

    Article  CAS  Google Scholar 

  33. Challita, E. J., Najem, J. S., Monroe, R., Leo, D. J. & Freeman, E. C. Encapsulating networks of droplet interface bilayers in a thermoreversible organogel. Sci. Rep. 8, 6494 (2018).

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by a European Research Council Advanced Grant and OxSyBio. F.G.D. and R.G.K. were supported by funding from the EPSRC & BBSRC Centre for Doctoral Training in Synthetic Biology (EP/L016494/1). D.J.L. is grateful to the European Union’s Horizon 2020 research and innovation programme for a Marie Curie Global Fellowship (657650). D.J.L. and C.J.H. acknowledge support from the US Army Research Office under contracts W911NF-09-D-0001 and W911NF-19-D-0001 for the Institute for Collaborative Biotechnologies. M.J.B. was supported by Merton College. J.B.S. was supported by funding from the Biotechnology and Biological Sciences Research Council (BB/M011224/1).

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Oxford, Oxford, UK

    Florence G. Downs, David J. Lunn, Michael J. Booth, Joshua B. Sauer, William J. Ramsay, R. George Klemperer & Hagan Bayley

  2. Materials Research Laboratory, University of California Santa Barbara, Santa Barbara, CA, USA

    David J. Lunn & Craig J. Hawker

  3. Materials Department, University of California Santa Barbara, Santa Barbara, CA, USA

    Craig J. Hawker

  4. Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA, USA

    Craig J. Hawker

Authors
  1. Florence G. Downs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David J. Lunn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. Booth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joshua B. Sauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William J. Ramsay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. George Klemperer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Craig J. Hawker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hagan Bayley
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

F.G.D. and D.J.L. designed, performed and analysed the experiments, with contributions from M.J.B., J.B.S., W.J.R. and R.G.K. F.G.D., D.J.L., M.J.B. and H.B. wrote the paper. D.J.L., M.J.B., C.J.H. and H.B. supervised the work.

Corresponding authors

Correspondence to David J. Lunn or Hagan Bayley.

Ethics declarations

Competing interests

H.B. is the Founder, a Director, a share-holder and a consultant for OxSyBio, a company engaged in the development of printed tissues and tissue-like materials. The other authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Materials information, methods and figures to accompany the manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Downs, F.G., Lunn, D.J., Booth, M.J. et al. Multi-responsive hydrogel structures from patterned droplet networks. Nat. Chem. 12, 363–371 (2020). https://doi.org/10.1038/s41557-020-0444-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41557-020-0444-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing