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4D-printed adaptive hydrogel tissue expanders for ear and breast reconstruction

Nature Biomedical Engineering (2026) Cite this article

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Abstract

Tissue expanders are widely used for organ and tissue reconstruction surgery. Hydrogel tissue expanders that swell in a biofluid are promising for minimally invasive operations. Nevertheless, clinical applications of existing hydrogel tissue expanders exhibit simple geometries, rapid swelling and insufficient mechanical performances. Here we develop a negatively charged polyelectrolyte hydrogel ink for light-based printing and prolonged yet large expansive profiles for surface organ and tissue reconstruction. This 4D-printed hydrogel tissue expander can be moulded in architecturally sophisticated constructs that adapt to the environment and show favourable mechanics without the need of external triggers for expansion. The ionization degree of the polyelectrolyte hydrogels is tunable by pH value in the surrounding medium and allows a volume equilibrium—swelling up to 10–30 times. In a rabbit model, we use the tissue expander for reconstruction of human-size ears and breasts, highlighting their multifold advantages over existing clinically adopted methods and thus future translation potentials.

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Fig. 1: Design and mechanism of AEHs.
The alternative text for this image may have been generated using AI.
Fig. 2: Synthesis–swelling relation and mechanical properties of AEHs.
The alternative text for this image may have been generated using AI.
Fig. 3: 4D printing of assorted AEH-based structures for isotropic and anisotropic expansion.
The alternative text for this image may have been generated using AI.
Fig. 4: In vitro swelling behaviours and mechanical properties of 4D-printed AEH-e-TEs.
The alternative text for this image may have been generated using AI.
Fig. 5: In vivo effectiveness and safety validations of 4D-printed AEH-TEs.
The alternative text for this image may have been generated using AI.
Fig. 6: In vivo competitive advantages of AEH-e-TEs over existing and clinical devices and evaluations of AEH-b-TEs for breast-reconstruction surgery.
The alternative text for this image may have been generated using AI.

Data availability

All data needed to evaluate the conclusions in the paper are included in the Article and/or Supplementary Information. Source data are provided with this paper.

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Acknowledgements

Support from the Brigham Research Institute Ministry of Science and ICT is acknowledged. D.W. further acknowledges the National Natural Science Foundation of China (82402936) for partial support. We appreciate the valuable suggestion from S. Zhan from the Clinical Laboratory of Plastic Surgery Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College.

Author information

Author notes

  1. These authors contributed equally: Di Wang, Jia-Qi Lü, Xiao Kuang.

  2. These authors jointly supervised this work: Yu Shrike Zhang, Haiyue Jiang.

Authors and Affiliations

  1. Plastic Surgery Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China

    Di Wang, Wen Chen & Haiyue Jiang

  2. Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, USA

    Di Wang, Xiao Kuang, Liming Lian, Sili Yi, Hossein Ravanbakhsh, Guosheng Tang, Maobin Xie, Carlos Ezio Garciamendez-Mijares, Prajwal Agrawal, Zixuan Wang, Sushila Maharjan & Yu Shrike Zhang

  3. Center for Advanced Laser Technology, Hebei University of Technology, Tianjin, People’s Republic of China

    Jia-Qi Lü & Jin-Song Li

  4. Hebei Key Laboratory of Advanced Laser Technology and Equipment, Tianjin, People’s Republic of China

    Jia-Qi Lü & Jin-Song Li

  5. Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI, USA

    Xiao Kuang

Authors
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Contributions

Y.S.Z., D.W. and X.K. conceived the idea. D.W., J.-Q.L., J.-S.L., C.E.G-M. and P.A. set up the printing system and participated in printing experiments. X.K. and H.R. performed simulation and theoretical analyses. D.W., J.-Q.L., L.L., J.-S.L., S.Y., G.T. and M.X. performed swelling tests and characterization experiments. D.W., W.C. and H.J. designed and performed animal experiments. Z.W., X.K. and D.W. designed the scheme and illustrations. S.M. contributed to methods for additional key experimental designs. D.W., J.-S.L., X.K., H.J. and Y.S.Z. wrote the paper, and all authors reviewed the manuscript. Y.S.Z. and H.J. supervised the project.

Corresponding authors

Correspondence to Haiyue Jiang or Yu Shrike Zhang.

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Competing interests

Y.S.Z. consulted for Allevi by 3D Systems; consults for PepGel; cofounded, consults for and holds options of Linton Lifesciences and Criocore; and sits on the scientific advisory board and holds options of Xellar Biosystems. The relevant interests are managed by the Brigham and Women’s Hospital. The other authors declare no competing interests.

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Nature Biomedical Engineering thanks Dong-Woo Cho, Michael Gelinsky and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information (download PDF )

Supplementary Figs. 1–37, Tables 1–6, captions for Videos 1–14, text and references.

Reporting Summary (download PDF )

Supplementary Video 1 (download MP4 )

Self-expansion of a 4D-printed AEH-e-TE in normal saline.

Supplementary Video 2 (download MP4 )

Finite element simulation of the self-expansion process of a 4D-printed AEH-e-TE.

Supplementary Video 3 (download MP4 )

Self-expansion of 4D-printed multi-material cylinders showing different swelling behaviours by design. Left: 2.0% PEGDA as the crosslinker. The pink cylinder swelled to a relatively small volume. Middle: 10.0%, 5.0%, 2.0% and 0.1% PEGDA as crosslinkers for the different layers from top to bottom. The cylinder indicated an anisotropic expansion. Right: 0.1% PEGDA as the crosslinker. The blue cylinder swelled to a relatively large volume.

Supplementary Video 4 (download MP4 )

A 4D-printed multi-material helix film coiling in normal saline.

Supplementary Video 5 (download MP4 )

AEH-TE expansion in the in vitro fluidic system.

Supplementary Video 6 (download MP4 )

Comparison of implantations of dialysed and un-dialysed AEH-e-TEs.

Supplementary Video 7 (download MP4 )

Recording of surgery using a 4D-printed AEH-e-TE with an initial α of 0.4.

Supplementary Video 8 (download MP4 )

Recording of surgery using a 4D-printed AEH-e-TE with an initial α of 0.

Supplementary Video 9 (download MP4 )

Mobilities of different types of implanted tissue expanders in expanded flaps.

Supplementary Video 10 (download MP4 )

Recording of surgery using a kidney-shaped silicone tissue expander.

Supplementary Video 11 (download MP4 )

Recording of surgery using a 4D-printed AEH-b-TE with an initial α of 0.4.

Supplementary Video 12 (download MP4 )

Recording of position correction for a mispositioned AEH-b-TE.

Supplementary Video 13 (download MP4 )

Stability of an implanted AEH-b-TE on day 12 in the expanded flap.

Supplementary Video 14 (download MP4 )

Recording of movements of rabbits implanted with AEH-b-TEs.

Supplementary Data (download XLSX )

Statistical source data for supplementary figures.

Source data

Source Data Fig. 1 (download XLSX )

Statistical source data.

Source Data Fig. 2 (download XLSX )

Statistical source data.

Source Data Fig. 3 (download XLSX )

Statistical source data.

Source Data Fig. 4 (download XLSX )

Statistical source data.

Source Data Fig. 5 (download XLSX )

Statistical source data.

Source Data Fig. 6 (download XLSX )

Statistical source data.

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Wang, D., Lü, JQ., Kuang, X. et al. 4D-printed adaptive hydrogel tissue expanders for ear and breast reconstruction. Nat. Biomed. Eng (2026). https://doi.org/10.1038/s41551-026-01681-z

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