Localized Hydrogen Release Driven by Mg-Pd Microgalvanic Cells from 3D-Printed Microneedles Reverses Redox Homeostasis for Psoriasis Treatment.

Abstract

Psoriasis therapy faces multiple challenges, including refractory, recurrence, and various comorbidities, attributed to its complex pathogenesis driven by aberrant keratinocyte proliferation, oxidative stress imbalance, and inflammation. These three factors form a vicious cycle, and cycle disruption holds great therapeutic potential for psoriasis. However, current therapies merely focus on symptom relief or anti-inflammatory effects alone with ignoring the essential cycle. To address the issues, a magnesium (Mg)-palladium (Pd) micro-galvanic cell (MP) with spontaneous electrochemical corrosion was constructed. MP released hydrogen (H2), inhibiting keratinocyte hyperproliferation, scavenging reactive oxygen species (ROS) and •OH, activating KEAP1‑NRF2 antioxidant signaling pathway, while generated Mg2+ exerted anti‑inflammatory effects. Furthermore, hollow microneedles loaded with MP (MP-MN) were fabricated via 3D printing to penetrate the stratum corneum for deep H2 delivery. In the imiquimod-induced psoriatic mouse model, MP‑MN topical treatment restored skin thickness, ameliorated oxidative stress, decreased splenic Th17/Treg ratio, and lowered both local and systemic pro‑inflammatory cytokine levels. Collectively, MP‑MN presented a comprehensive strategy for anti-inflammatory, antioxidant, and immune-regulatory effects in psoriasis, broadening the applications of H2 and micro-galvanic cells in skin disorders.

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