Anti-inflammasome bio-heterojunction (AI-bioHJ): Revolutionizing diabetic wound healing with in situ self-transformation and programmed gas therapy

Persistent activation of NLRP3 inflammasomes in infectious diabetic wounds lead to uncontrolled inflammation. Hydrogen sulfide (H2S) gas therapy shows promise in inhibiting inflammasomes. However, on-demand delivery of H2S is challenging, as its biological characteristics are Janus-faced. Herein, we present the anti-inflammasome bio-heterojunction (AI-bioHJ), comprising FeS, Cu2O, and glucose oxidase (GOx), capable of H2S gas evolution and in situ self-transformation to accelerate diabetic wound healing. In this system, AI-bioHJ release H2S to inhibit NLRP3 inflammasomes and recycle excess H2S through a reaction between Cu2O and H2S, maintaining a low H2S concentration while upgrading type I FeS/Cu2O to Z-scheme FeS/CuS bioHJ, and markedly enhancing phototherapy. Additionally, GOx depletes local glucose to generate H2O2, promoting Fenton-like reactions and rapid pathogenic elimination. In vivo and in vitro assessments confirm AI-bioHJ effectively eliminate pathogen, inhibit inflammasomes and facilitate diabetic wound healing. Transcriptome analysis indicates that the FoxO–autophagy axis may mediate the anti-inflammasome effects. Altogether, our work provides enlightenments into programmed H2S-releasing bioHJ for remedying diabetic wounds.