Reshaping psoriasis topical therapy: Continuous hydrogenation orchestrates ‘redox-metabolic homeostasis’ for efficient remission and relapse intervention

Psoriasis represents a globally prevalent and chronic dermatological disorder, characterized by persistent hyperkeratosis, self-sustaining inflammatory cycles, and frequent relapse, posing substantial challenges for conventional therapies of compromised efficacy and biosafety. Here, we introduce a transformative strategy of hydrogen-mediated topical psoriasis therapy based on the construction of an in-situ formed, microbubble hydrogel that facilitates significant H 2 generation and subsequently prolonged delivery. By fabricating and incorporating MgH 2 nanoparticles into an amphiphilic, thermosensitive hydrogel via self-assembly in saline, the hydrogen evolution reaction, generated microbubble morphology and storage can be well controlled, reaching optimized H 2 release profile at saturated concentration (∼0.8 mM) over days. We demonstrate marked alleviation of psoriasis-like pathologies with this local hydrogen treatment in vitro and in vivo , revealing superior efficacy compared to both Imiquimod-induced mice model and clinical Calcipotriol drug. Mechanistically, we disclose continuous hydrogenation directly suppresses psoriatic keratinocyte hyperproliferation via anti-Warburg effect and energy metabolic reprogramming through the PKM2-mediated pathway, and meanwhile coordinating redox homeostasis restoration which further disrupts the inflammation-immune feedback loop. We also identify the potency of this H 2 -regulated energy metabolism strategy in preventing psoriasis recurrence. Collectively, this work delivers a proof-of-concept of hydrogen-mediated psoriasis energy therapy (HPET) with translatable promise for potentiating long-term management. • Engineered hydrogenated microbubble gel enables local, adequate, and durable H 2 release. • Mechanistic insights reveal H 2 selectively downregulates keratinocyte energy metabolism. • Topical hydrogen-mediated psoriasis energy therapy (HPET) mitigatesits onset and recurrence with high biocompatibility.