Integrated O 2 and H 2 Gas Therapy via Microneedle‐Assisted Photocatalytic Water Splitting for Accelerating Diabetic Full‐Thickness Skin Wound Healing

ABSTRACT Impaired wound healing in diabetes is closely associated with cellular ferroptosis. Microneedle‐assisted gas therapy exerts molecular regulation of ferroptosis, representing a promising approach for accelerating diabetic wound healing. To date, O 2 and H 2 gas therapies have consistently been conducted independently and have never been integrated into a single system. Whether and how their synergy might be realized remains a defining challenge. Herein, we propose a concept of integrated O 2 and H 2 gas therapy, demonstrated by fabricating a gas‐producing microneedle material. Platinum@MIL‐101(Fe)‐NH 2 @phosphotungstic acid (PMP) nanoparticles are synthesized as a visible light‐driven photocatalyst for H 2 and O 2 co‐evolution. The rational design of a spatially separated structure boosts their photocatalytic efficiency under physiological conditions. PMP nanoparticles are further incorporated with bilayer gelatin methacryloyl (GelMA)/PMP composite microneedles (denoted as GPM microneedles). The obtained GPM microneedles enable transdermal delivery of PMP nanoparticles for integrated O 2 and H 2 gas therapy, and demonstrate desirable biocompatibility and pro‐regenerative effects. The mechanism of integrated O 2 and H 2 gas therapy has been identified as a TNFAIP3/hnRNPA1 ubiquitination/ferroptosis signaling axis, establishing for the first time a direct link to ferroptosis. In conclusion, this study yields a transformative concept and a ferroptosis‐targeting microneedle material with well‐defined molecular mechanism for diabetic wound management.