Reactive signaling molecules such as hydrogen sulfide (H2S) regulate protein function and cellular redox balance, yet their instability makes precise delivery in biological systems challenging. Existing bioelectronic platforms primarily target stable molecules and often lack the ability to control transient molecules with spatiotemporal precision. We develop a bioelectronic platform that uses electrochemical reactions to directly generate and deliver H2S from biocompatible thiosulfate precursors near living cells. Through electrocatalyst screening, theoretical modeling, and product analysis, we demonstrate that biocompatible metal cathodes with low metal-hydrogen binding energy catalyze H2S production while suppressing side reactions. Programmable electronic inputs, including electrolysis time and applied voltage, quantitatively control distance- and time-dependent H2S release at the bioelectronic interface while maintaining physiological compatibility. This spatiotemporally modulated H2S synthesis enables on-demand activation of ion channels through protein sulfhydration and restoration of intracellular redox balance under oxidative stress. Our platform broadens the functional scope of bioelectronics and establishes electrosynthesis as a modality for dynamic communication between electronics and biology.
Lim et al. (Wed,) studied this question.