A Promising Biomimetic Hydrogen Sulfide System for Advancing Inflammatory Disease Treatment

Abstract Hydrogen sulfide (H ₂ S) exhibits a Janus‐faced nature in the regulation of inflammatory diseases, acting as both a therapeutic agent and a pathological aggravator. Effectively harnessing its beneficial effects while mitigating its harmful impacts is pivotal for advancing H ₂ S‐based therapies. Here, an innovative H ₂ S supply system is introduced that enables H ₂ S to primarily exhibit its therapeutic effects. Unlike conventional synthetic H ₂ S donor‐based strategies, a biomimetic H ₂ S supply system (termed CP) is presented that mimics endogenous enzymatic H ₂ S production. The CP sustainably produces H ₂ S at a constant rate throughout the dosing period, ensuring therapeutic benefits while avoiding toxicity. Furthermore, by functionalizing CP with hyaluronic acid, the resulting system (CPH) not only achieves targeted delivery to inflammatory bowel disease (IBD) tissues but also provides controllable H ₂ S production within the diseased microenvironment. Consequently, CPH significantly mitigates immune inflammation, promotes intestinal epithelial barrier repair, and modulates gut microbiota by sustainably and constantly supplying the multifunctional H ₂ S. This study revolutionizes the H ₂ S supply strategies and provides new insights into gas‐based therapies.