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Percolation-induced gel–gel phase separation in a dilute polymer network

Nature Materials volume 22, pages 1564–1570 (2023)Cite this article

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Abstract

Cosmic large-scale structures, animal flocks and living tissues can be considered non-equilibrium organized systems created by dissipative processes. Replicating such properties in artificial systems is still difficult. Herein we report a dissipative network formation process in a dilute polymer–water mixture that leads to percolation-induced gel–gel phase separation. The dilute system, which forms a monophase structure at the percolation threshold, spontaneously separates into two co-continuous gel phases with a submillimetre scale (a dilute-percolated gel) during the deswelling process after the completion of the gelation reaction. The dilute-percolated gel, which contains 99% water, exhibits unexpected hydrophobicity and induces the development of adipose-like tissues in subcutaneous tissues. These findings support the development of dissipative structures with advanced functionalities for distinct applications, ranging from physical chemistry to tissue engineering.

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Fig. 1: Schematic of the processes for yielding the dilute-percolated and c* gels.
Fig. 2: Clouding during gelation and thermodynamically stable submillimetre-scale phase-separated structure.
Fig. 3: Formation process of GGPS.
Fig. 4: Biological response with hydrogels.

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Data availability

Data generated or analysed during this study are included in the main and Supplementary Information files. Further data are available from the corresponding authors upon request. Source data are provided with this paper.

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Acknowledgements

This study was supported by the Japan Society for the Promotion of Science (JSPS) through Grants-in-Aid for JSPS Research Fellows grant number 20J01344 to S.I., Early Career Scientists grant number 19K14672 to N.S., Scientific Research (B) grant numbers 22H01187 to N.S. and 22H02135 to X.L., Scientific Research (A) grant numbers 21H04688 to T.Sakai. and 21H04952 to U.C., Innovative Areas grant numbers 19H05794 and 19H05795 to Y.O. and Transformative Research Areas grant number 20H05733 to T.Sakai. This study was also supported by the Japan Science and Technology Agency (JST) PRESTO grant number JPMJPR1992 to T.U., FOREST JPMJFR201Z to X.L., JPMJFR225N to H.H., CREST grant number JPMJCR1992 to T.Sakai., JPMJCR1852 and JPMJCR20E2 to Y.O., Moon-shot R&D grant number 1125941 to T.Sakai., JPMJMS2025-14 to Y.O. and Data Creation and Utilization-Type Material Research and Development Project (JPMXP1122714694) to T.Sakai.

Author information

Authors and Affiliations

  1. Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

    Shohei Ishikawa, Yasuhide Iwanaga, Naoyuki Sakumichi & Takamasa Sakai

  2. Department of Materials Physics, Graduate School of Engineering, Nagoya University, Nagoya, Japan

    Takashi Uneyama

  3. Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan

    Xiang Li

  4. Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Hironori Hojo

  5. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

    Ikuo Fujinaga, Takuya Katashima & Ung-il Chung

  6. Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Taku Saito

  7. Laboratory for Cell Polarity Regulation, RIKEN Center for Biosystems Dynamics Research (BDR), Suita, Japan

    Yasushi Okada

  8. Department of Cell Biology, Department of Physics, Universal Biology Institute (UBI) and International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo, Japan

    Yasushi Okada

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  1. Shohei Ishikawa
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Contributions

All authors contributed to writing the paper and discussing the results. Experiments were planned, conducted and analysed by S.I., Y.I., T.U., X.L. and I.F. Discussions regarding the mechanism of GGPS involved S.I., N.S., T.K. and T.Sakai. CLSM observation was performed by S.I. and Y.O. Animal experiments were performed by S.I. and Y.I.; N.S. and T.Sakai. conceived the idea and supervised the project.

Corresponding authors

Correspondence to Naoyuki Sakumichi or Takamasa Sakai.

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Competing interests

T.S. is an inventor on a patent application (WO2020027016) that describes the use of this hydrogel with GGPS.

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Peer review information

Nature Materials thanks Jens-Uwe Sommer and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–10.

Reporting Summary

Supplementary Video 1

Inner structure of dilute-percolated gel. 1.7 mm x 2 mm x 0.1 mm volume is shown with a grid size of 200 µm for x and y.

Supplementary Video 2

Three-dimensional phase-separated structure of dilute-percolated gel. Same view as Fig 1c. 400 µm x 400 µm x 200 µm volume is shown with a grid size of 50 µm.

Supplementary Video 3

Inner structure of c* gel. 1.7 mm x 2 mm x 0.1 mm volume is shown with a grid size of 200 µm for x and y.

Supplementary Video 4

Three-dimensional structure of dilute-percolated gel. Same view as Fig 1c. 400 µm x 400 µm x 200 µm volume is shown with a grid size of 50 µm.

Supplementary Video 5

Formation of phase-separated structure.

Supplementary Video 6

Formation of phase-separated structure during cooling process. Shown with pseudo-color to visualize density changes better. Scales are shown in the movie.

Supplementary Video 7

Dilute-percolated gel implanted subcutaneously in rats.

Supplementary Video 8

The c* gel implanted subcutaneously in rats.

Source Data Supplementary Fig. 1

Statistical source data for Supplementary Fig. 1.

Source Data Supplementary Fig. 3

Statistical source data for Supplementary Fig. 3.

Source Data Supplementary Fig. 5

Statistical source data for Supplementary Fig. 5.

Source Data Supplementary Fig. 6

Statistical source data for Supplementary Fig. 6.

Source Data Supplementary Fig. 7

Statistical source data for Supplementary Fig. 7.

Source data

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

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Ishikawa, S., Iwanaga, Y., Uneyama, T. et al. Percolation-induced gel–gel phase separation in a dilute polymer network. Nat. Mater. 22, 1564–1570 (2023). https://doi.org/10.1038/s41563-023-01712-z

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