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Psoriasis is a widespread and chronic skin disorder that is prevalent globally. Its characteristics include continuous hyperkeratosis, self-sustaining inflammatory cycles, and frequent recurrence, presenting significant challenges to traditional therapeutic approaches in terms of efficacy and biological safety. This article introduces a transformative strategy for local psoriasis treatment based on the in situ formation of microbubble hydrogels, which promotes the generation of a large amount of H2 and extends the delivery time. By self-assembling in saline, MgH2 nanoparticles are incorporated into a amphiphilic, thermosensitive hydrogel, allowing the hydrogen evolution reaction, the morphology of the generated microbubbles, and storage to be well controlled. At a saturated concentration (approximately 0.8 mM), the optimal H2 release curve is achieved within several days. We have demonstrated that this local hydrogen treatment significantly alleviates psoriasis-like pathology both in vitro and in vivo, with superior efficacy compared to the imizolazole-induced mouse model and clinical calcitriol drugs. Mechanistically, we reveal that continuous hydrogenation inhibits excessive proliferation and energy metabolism reprogramming of psoriatic keratinocytes through the PKM2-mediated pathway, while coordinating redox homeostasis restoration and further disrupting the inflammatory immune feedback loop. We have also identified the effectiveness of this H2-regulated energy metabolism strategy in preventing psoriasis recurrence. Overall, this work provides a proof-of-concept for hydrogen-mediated psoriasis energy therapy (HPET) and holds promise for enhancing long-term therapeutic efficacy. References:
DOI: 10.1016/j.bioactmat.2026.03.018
