The Landscape of Smart Biomaterial-Based Hydrogen Therapy.

Hydrogen (H) therapy is an emerging, novel, and safe therapeutic modality that uses molecular hydrogen for effective treatment. However, the impact of H therapy is limited because hydrogen molecules predominantly depend on the systemic administration of H 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 and control its release. In this review, the development process, stimuli-responsive release strategies, and potential therapeutic mechanisms of biomaterial-based H therapy are summarized. H therapy. Specifically, the produced H 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 can further act as signal molecules to regulate key pathways for disease treatment. The current opportunities and challenges of H-based therapy are discussed, and the future research directions of biomaterial-based H therapy for clinical applications are emphasized.