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.

Strong tough hydrogels via the synergy of freeze-casting and salting out

Abstract

Natural load-bearing materials such as tendons have a high water content of about 70 per cent but are still strong and tough, even when used for over one million cycles per year, owing to the hierarchical assembly of anisotropic structures across multiple length scales1. Synthetic hydrogels have been created using methods such as electro-spinning2, extrusion3, compositing4,5, freeze-casting6,7, self-assembly8 and mechanical stretching9,10 for improved mechanical performance. However, in contrast to tendons, many hydrogels with the same high water content do not show high strength, toughness or fatigue resistance. Here we present a strategy to produce a multi-length-scale hierarchical hydrogel architecture using a freezing-assisted salting-out treatment. The produced poly(vinyl alcohol) hydrogels are highly anisotropic, comprising micrometre-scale honeycomb-like pore walls, which in turn comprise interconnected nanofibril meshes. These hydrogels have a water content of 70–95 per cent and properties that compare favourably to those of other tough hydrogels and even natural tendons; for example, an ultimate stress of 23.5 ± 2.7 megapascals, strain levels of 2,900 ± 450 per cent, toughness of 210 ± 13 megajoules per cubic metre, fracture energy of 170 ± 8 kilojoules per square metre and a fatigue threshold of 10.5 ± 1.3 kilojoules per square metre. The presented strategy is generalizable to other polymers, and could expand the applicability of structural hydrogels to conditions involving more demanding mechanical loading.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Fabrication and hierarchical structures of HA-PVA hydrogels.
Fig. 2: Mechanical properties and structural evolution of HA-PVA hydrogel.
Fig. 3: Hydrogel structure and mechanical properties relationship.
Fig. 4: Tunable mechanical properties and generality of hydrogels produced by ice-templating-assisted salting out.

Data availability

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

References

  1. 1.

    Maganaris, C. N. & Paul, J. P. In vivo human tendon mechanical properties. J. Physiol. (Lond.) 521, 307–313 (1999).

    CAS  Article  Google Scholar 

  2. 2.

    Gu, L., Jiang, Y. & Hu, J. Scalable spider-silk-like supertough fibers using a pseudoprotein polymer. Adv. Mater. 31, 1904311 (2019).

    CAS  Article  Google Scholar 

  3. 3.

    Hong, S. et al. 3D printing of highly stretchable and tough hydrogels into complex, cellularized structures. Adv. Mater. 27, 4034–4040 (2015).

    Article  Google Scholar 

  4. 4.

    Xiang, C. et al. Stretchable and fatigue-resistant materials. Mater. Today 34, 7–16 (2020).

    CAS  Article  Google Scholar 

  5. 5.

    Huang, Y. et al. Energy-dissipative matrices enable synergistic toughening in fiber reinforced soft composites. Adv. Funct. Mater. 27, 1605350 (2017).

    Article  Google Scholar 

  6. 6.

    Zhang, H. et al. Aligned two- and three-dimensional structures by directional freezing of polymers and nanoparticles. Nat. Mater. 4, 787–793 (2005).

    ADS  CAS  Article  Google Scholar 

  7. 7.

    Zhang, H. Ice Templating and Freeze-Drying for Porous Materials and their Applications (Wiley-VCH, 2018).

  8. 8.

    Qin, H., Zhang, T., Li, N., Cong, H. P. & Yu, S. H. Anisotropic and self-healing hydrogels with multi-responsive actuating capability. Nat. Commun. 10, 2202 (2019).

    ADS  Article  Google Scholar 

  9. 9.

    Mredha, M. T. I. et al. Anisotropic tough multilayer hydrogels with programmable orientation. Mater. Horiz. 6, 1504–1511 (2019).

    CAS  Article  Google Scholar 

  10. 10.

    Mredha, M. T. I. et al. A facile method to fabricate anisotropic hydrogels with perfectly aligned hierarchical fibrous structures. Adv. Mater. 30, 1704937 (2018).

    Article  Google Scholar 

  11. 11.

    Wegst, U. G. K., Bai, H., Saiz, E., Tomsia, A. P. & Ritchie, R. O. Bioinspired structural materials. Nat. Mater. 14, 23–36 (2015).

    ADS  CAS  Article  Google Scholar 

  12. 12.

    Sun, J.-Y. et al. Highly stretchable and tough hydrogels. Nature 489, 133–136 (2012).

    ADS  CAS  Article  Google Scholar 

  13. 13.

    Gong, J. P., Katsuyama, Y., Kurokawa, T. & Osada, Y. Double-network hydrogels with extremely high mechanical strength. Adv. Mater. 15, 1155–1158 (2003).

    CAS  Article  Google Scholar 

  14. 14.

    Hu, X., Vatankhah-Varnoosfaderani, M., Zhou, J., Li, Q. & Sheiko, S. S. Weak hydrogen bonding enables hard, strong, tough, and elastic hydrogels. Adv. Mater. 27, 6899–6905 (2015).

    CAS  Article  Google Scholar 

  15. 15.

    Lin, P., Ma, S., Wang, X. & Zhou, F. Molecularly engineered dual-crosslinked hydrogel with ultrahigh mechanical strength, toughness, and good self-recovery. Adv. Mater. 27, 2054–2059 (2015).

    CAS  Article  Google Scholar 

  16. 16.

    He, Q., Huang, Y. & Wang, S. Hofmeister effect-assisted one step fabrication of ductile and strong gelatin hydrogels. Adv. Funct. Mater. 28, 1705069 (2018).

    Article  Google Scholar 

  17. 17.

    Lin, S. et al. Anti-fatigue-fracture hydrogels. Sci. Adv. 5, eaau8528 (2019).

    ADS  Article  Google Scholar 

  18. 18.

    Bai, R., Yang, J., Morelle, X. P. & Suo, Z. Flaw-insensitive hydrogels under static and cyclic loads. Macromol. Rapid Commun. 40, 1800883 (2019).

    Article  Google Scholar 

  19. 19.

    Lin, S., Liu, J., Liu, X. & Zhao, X. Muscle-like fatigue-resistant hydrogels by mechanical training. Proc. Natl Acad. Sci. USA 116, 10244–10249 (2019).

    ADS  CAS  Article  Google Scholar 

  20. 20.

    Illeperuma, W. R. K., Sun, J. Y., Suo, Z. & Vlassak, J. J. Fiber-reinforced tough hydrogels. Extreme Mech. Lett. 1, 90–96 (2014).

    Article  Google Scholar 

  21. 21.

    Lin, S. et al. Design of stiff, tough and stretchy hydrogel composites via nanoscale hybrid crosslinking and macroscale fiber reinforcement. Soft Matter 10, 7519–7527 (2014).

    ADS  CAS  Article  Google Scholar 

  22. 22.

    King, D. R., Okumura, T., Takahashi, R., Kurokawa, T. & Gong, J. P. Macroscale double networks: design criteria for optimizing strength and toughness. ACS Appl. Mater. Interfaces 11, 35343–35353 (2019).

    CAS  Article  Google Scholar 

  23. 23.

    Fan, H. & Gong, J. P. Fabrication of bioinspired hydrogels: challenges and opportunities. Macromolecules 53, 2769–2782 (2020).

    ADS  CAS  Article  Google Scholar 

  24. 24.

    Zhao, X. Multi-scale multi-mechanism design of tough hydrogels: building dissipation into stretchy networks. Soft Matter 10, 672–687 (2014).

    ADS  CAS  Article  Google Scholar 

  25. 25.

    Wang, Z. et al. Stretchable materials of high toughness and low hysteresis. Proc. Natl Acad. Sci. USA 116, 5967–5972 (2019).

    ADS  CAS  Article  Google Scholar 

  26. 26.

    Iwaseya, M., Watanabe, M., Yamaura, K., Dai, L. X. & Noguchi, H. High performance films obtained from PVA/Na2SO4/H2O and PVA/CH3COONa/H2O systems. J. Mater. Sci. 40, 5695–5698 (2005).

    ADS  CAS  Article  Google Scholar 

  27. 27.

    Zhang, Y. & Cremer, P. S. Interactions between macromolecules and ions: the Hofmeister series. Curr. Opin. Chem. Biol. 10, 658–663 (2006).

    CAS  Article  Google Scholar 

  28. 28.

    van de Witte, P., Dijkstra, P. J., Van Den Berg, J. W. A. & Feijen, J. Phase separation processes in polymer solutions in relation to membrane formation. J. Membr. Sci. 117, 1–31 (1996).

    Article  Google Scholar 

  29. 29.

    Lake, G. J. & Thomas, A.G. The strength of highly elastic materials. Proc. R. Soc. A 300, 108–119 (1967).

    ADS  CAS  Google Scholar 

  30. 30.

    Kinloch, A. J. & Young, R. J. (eds) Fracture Behaviour of Polymers (Springer Science & Business Media, 1984).

  31. 31.

    Johnston, I. D., McCluskey, D. K., Tan, C. K. L. & Tracey, M. C. Mechanical characterization of bulk Sylgard 184 for microfluidics and microengineering. J. Micromech. Microeng. 24, 035017 (2014).

  32. 32.

    Wood, L. A. Uniaxial extension and compression in stress-strain relations of rubber. Rubber Chem. Technol. 51, 840–851 (1978).

    Article  Google Scholar 

  33. 33.

    Ebrahimi, D. et al. Silk – its mysteries, how it is made, and how it is used. ACS Biomater. Sci. Eng. 1, 864–876 (2015).

    CAS  Article  Google Scholar 

  34. 34.

    Long, R. & Hui, C. Y. Fracture toughness of hydrogels: measurement and interpretation. Soft Matter 12, 8069–8086 (2016).

    ADS  CAS  Article  Google Scholar 

  35. 35.

    Jiang, Z. GIXSGUI: a MATLAB toolbox for grazing-incidence X-ray scattering data visualization and reduction, and indexing of buried three-dimensional periodic nanostructured films. J. Appl. Cryst. 48, 917–926 (2015).

    CAS  Article  Google Scholar 

  36. 36.

    Peppas, N. A. & Merrill, E. W. Differential scanning calorimetry of crystallized PVA hydrogels. J. Appl. Polym. Sci. 20, 1457–1465 (1976).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This research was supported by NSF CAREER award 1724526, AFOSR awards FA9550-17-1-0311, FA9550-18-1-0449 and FA9550-20-1-0344, and ONR awards N000141712117 and N00014-18-1-2314. X.Z. acknowledges Shanghai Municipal Government 18JC1410800 and National Natural Science Foundation of China 51690151. This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract number DE-AC02-06CH11357.

Author information

Affiliations

Authors

Contributions

M.H., S.W. and X.H. conceived the concept. X.H. supervised the project. M.H., S.W., Z.C. and Y.Z. conducted the experiments. J.S. and H.Z. helped with the WAXS and SAXS measurements. M.H., S.W. and X.H. wrote the manuscript. All authors contributed to the analysis and discussion of the data.

Corresponding author

Correspondence to Ximin He.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature thanks Jiaxi Cui, Sylvain Deville and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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

Extended data figures and tables

Extended Data Fig. 1 Micro- and nanostructures and stress–strain curves of PVA hydrogels fabricated by different methods and their corresponding fracture energies and critical strains.

a, ‘DF + Salting out’ denotes a hydrogel prepared by directional freezing of a 5% PVA solution and salting out in 1.5 M sodium citrate solution for 24 h. b, ‘F + Salting out’ represents a hydrogel prepared by non-directional freezing of a 5% PVA solution in the fridge and salting out in 1.5 M sodium citrate solution for 24 h. c, ‘DFT-3 cycle’ denotes a hydrogel prepared by directional freezing and thawing of a 5% PVA solution for three cycles. d, ‘FT-3 cycle’ indicates a hydrogel prepared by non-directional freezing in the fridge and thawing of a 5% PVA solution for three cycles. e, ‘Chemical Crosslinking’ represents a hydrogel prepared by mixing 0.5% glutaraldehyde and 0.5% hydrochloric acid into a 5% PVA solution for gelation. f, Salting out resulted in non-gelation. Only weak globules of loose and random nanofibrils were made by directly adding a 1.5 M sodium citrate solution into a 5% PVA solution. Panels ac are the same as Fig. 3a–c.

Extended Data Fig. 2 Mechanical properties of HA-PVA hydrogel compared to those of PVA hydrogels prepared by ice-templating alone or salting out alone.

a, b, The HA-PVA hydrogels are shown as red stars, and black squares correspond to the ice-templated PVA hydrogels (a) and the salting out PVA hydrogels (b). The data used are summarized in Supplementary Tables 1, 2.

Extended Data Fig. 3 Fatigue test of HA-20PVA hydrogels.

a, Fatigue threshold of HA-20PVA. When loading above the threshold energy release rate (ε = 400%), the crack propagates slowly. N, number of cycles. b, Validation of fatigue threshold with an energy release rate slightly lower than the fatigue threshold. No crack propagation or failure was observed for 30,000 loading cycles.

Extended Data Fig. 4 Water content and fracture energy of the HA-PVA hydrogels.

a, Water content of HA-xPVA hydrogels for x = 2, 5, 10 and 20. The error bars (1 s.d. from five measured samples) were obtained from five measured samples with standard deviations of 1.72%, 2.29%, 2.69% and 2.43% for x = 2, 5, 10 and 20, respectively. b, Fracture energy of HA-xPVA hydrogels, x = 2, 5, 10 and 20, measured by pure shear tests. The error bars (1 s.d. from five measured samples) were obtained from five measured samples with standard deviations of 0.16, 4.83, 5.44 and 5.62 kJ m−2 for x = 2, 5, 10 and 20, respectively.

Extended Data Fig. 5 HA-alginate hydrogels compared with calcium-alginate hydrogels.

a, Photograph of HA-5alginate hydrogel. b, Tensile stress–strain curve of a HA-5alginate hydrogel compared to that of a regular calcium-alginate hydrogel. Scale bar, 5 mm.

Supplementary information

Supplementary Information

This file includes a list of materials, Supplementary Text, Supplementary References, Supplementary Figs. 1–13, Supplementary Tables 1–3 and full captions for Videos 1 to 4.

Video 1

Tensile loading of HA-5PVA dog-bone shaped hydrogel specimen.

Video 2

Tensile loading of HA-5PVA hydrogel with pre-made crack.

Video 3

Tensile loading of HA-20PVA hydrogel with pre-made crack.

Video 4

Tensile loading of 5PVA hydrogel prepared by non-directional freezing and salting out with pre-made crack.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hua, M., Wu, S., Ma, Y. et al. Strong tough hydrogels via the synergy of freeze-casting and salting out. Nature 590, 594–599 (2021). https://doi.org/10.1038/s41586-021-03212-z

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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