Abstract
Molecular hydrogen (H2) protects organs from reactive oxygen species damage associated with ischemia–reperfusion (I/R) injury. Existing H2 delivery methods, such as gas inhalation and H2-rich water consumption, target the entire body and experience leakage during administration. Here we engineer a portable hydrogel electrochemical cell that enables on-demand H2 production via the hydrogen evolution reaction. The system enables H2 controlled generation, localized storage and sustained diffusion to the tissue–device interface, with better controllability and sustainability. We conduct a thorough study of H2 evolution and dynamics in the hydrogel system, evaluating the influence of hydrogel polymer composition on the hydrogen evolution reaction kinetics, bubble morphologies and storage. We validate its protective effects (1) in vitro with cardiomyocytes and keratinocytes, (2) ex vivo in I/R hearts and (3) in vivo in skin I/R pressure ulcers. These findings demonstrate the potential of the hydrogel electrochemical cell design for efficient and sustainable H2 delivery in I/R therapy, which could be broadly applied in other gas-based therapies and drug delivery research.
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Data availability
The research findings presented in this study are supported by data included in the Article and Supplementary Information. Source data are provided with this paper and are publicly available via GitHub at https://github.com/wenli-web/Hydrogen-evolution-in-hydrogel-electrochemical-cell/tree/main.
Code availability
Scripts used for data analysis and Bluetooth user interface in this study are available via GitHub at https://github.com/wenli-web/Hydrogen-evolution-in-hydrogel-electrochemical-cell/tree/main.
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Acknowledgements
We thank K. M. Watters for scientific editing of the manuscript, Z. Zhou for providing H2 for GC calibration, and J. Solaway for helpful insights and discussion. B.T. acknowledges support from the US Army Research Office (W911NF-24-1-0053), the National Institute of Health (1R01EB036091-01) and the National Science Foundation (NSF CBET-2422962 and NSF OMA-2121044). L.J. acknowledges support from the National Science Foundation (NSF CMMI-2403592). This work used computational and storage services associated with the Hoffman2 Shared Cluster provided by the Institute for Digital Research and Education’s Research Technology Group at the University of California, Los Angeles. We would like to thank the University of Chicago Animal Resources Center (RRID: SCR_021806). This work made use of the Pritzker Nanofabrication Facility at the Pritzker School of Molecular Engineering at the University of Chicago, which receives support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), a node of the National Science Foundation’s National Nanotechnology Coordinated Infrastructure (RRID: SCR_022955). Parts of this work were carried out at the Soft Matter Characterization Facility and Integrated Small Animal Imaging Research Resource (iSAIRR imaging center) of the University of Chicago.
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Authors and Affiliations
Contributions
B.T. supervised the research. W.L. and B.T. initiated and conceived the hydrogel electrochemical cell concept. W.L. conducted most of the data collection on materials synthesis, characterization and in vivo rodent experiments. W.L. designed and fabricated all the devices. J.Z. and W.L. conducted most of the data collection for the in vitro cell and ex vivo heart experiments. R.N., P. Lopes and T.G. assisted W.L. with the electronics design. J.Y. assisted with the in vivo rodent experiments. A.K. assisted with the diffusion simulation. C.W. and L.J. assisted with the mechanical simulation for bubble morphology. H.-M.T. assisted with the CT characterization. B.L., C.Y., P. Li, C.S. and S.K. assisted with the materials preparation and characterization. W.L. and J.Z. conducted all the subsequent data analysis. L.L.S. provided insight in manuscript preparation. W.L., J.Z. and B.T. prepared the manuscript, with input from all other authors.
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Competing interests
The work highlighted in this manuscript is the subject of a pending patent application filed with the USPTO and owned by The University of Chicago. B.T. and W.L. are the inventors. A company called hPad was established based on the work. The other authors declare no competing interests.
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Nature Chemical Engineering thanks Seung-Pyo Lee, Yi Zhang, Yunlong Zhao 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 Tables 1 and 2, Figs. 1–51, Captions for Supplementary Videos 1–7 and Methods.
Supplementary Video 1
Ti wire in solution producing H2 with 0.5-mA charge for 5 min. The video is played at 10× speed.
Supplementary Video 2
Ti wire in 3% hydrogel producing H2 with 0.5-mA charge for 5 min. The video is played at 10× speed.
Supplementary Video 3
Ti wire in 6% hydrogel producing H2 with 0.5-mA charge for 5 min. The video is played at 10× speed.
Supplementary Video 4
Ti wire in 10% hydrogel producing H2 with 0.5-mA charge for 5 min. The video is played at 10× speed.
Supplementary Video 5
Ti wire in 3% PVA solution producing H2 with 0.5-mA charge for 3 min. The video is played at 10× speed.
Supplementary Video 6
Ti wire–hydrogel–air interface producing H2 with 0.5-mA charge. The hydrogel is 10%. The video is played at 10× speed.
Supplementary Video 7
MEA–hydrogel device flame exposure test after 5-mA, 6-min charging.
Source data
Source Data Fig. 2
Statistical source data.
Source Data Fig. 3
Statistical source data.
Source Data Fig. 4
Statistical source data, and raw data of the LVP and ECG signals.
Source Data Fig. 5
Statistical source data.
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Li, W., Zhang, J., Nith, R. et al. Hydrogen evolution and dynamics in hydrogel electrochemical cells for ischemia–reperfusion therapy. Nat Chem Eng 2, 484–497 (2025). https://doi.org/10.1038/s44286-025-00259-x
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DOI: https://doi.org/10.1038/s44286-025-00259-x
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