The Landscape of Smart Biomaterial‐Based Hydrogen Therapy

Abstract Hydrogen (H 2 ) therapy is an emerging, novel, and safe therapeutic modality that uses molecular hydrogen for effective treatment. However, the impact of H 2 therapy is limited because hydrogen molecules predominantly depend on the systemic administration of H 2 gas, which cannot accumulate at the lesion site with high concentration, thus leading to limited targeting and utilization. Biomaterials are developed to specifically deliver H 2 and control its release. In this review, the development process, stimuli‐responsive release strategies, and potential therapeutic mechanisms of biomaterial‐based H 2 therapy are summarized. H 2 therapy. Specifically, the produced H 2 from biomaterials not only can scavenge free radicals, such as reactive oxygen species (ROS) and lipid peroxidation (LPO), but also can inhibit the danger factors of initiating diseases, including pro‐inflammatory cytokines, adenosine triphosphate (ATP), and heat shock protein (HSP). In addition, the released H 2 can further act as signal molecules to regulate key pathways for disease treatment. The current opportunities and challenges of H 2 ‐based therapy are discussed, and the future research directions of biomaterial‐based H 2 therapy for clinical applications are emphasized.