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.