Hydrogen evolution and dynamics in hydrogel electrochemical cells for ischemia-reperfusion therapy

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.