In-Situ Hydrogen-Generating Injectable Short Fibers for Osteoarthritis Treatment by Alleviating Oxidative Stress

Hydrogen (H₂) has great potential in the treatment of osteoarthritis, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study developed a short-fiber injectable material that can continuously generate hydrogen in situ to eliminate reactive oxygen species (ROS), alleviate oxidative stress and inflammation, and promote tissue repair. We prepared H-Si nanosheets with high hydrogen generation efficiency using a wet chemical exfoliation method and combined them with GelMA short fibers via electrospinning technology, achieving the in situ delivery of H-Si nanosheets and regulated hydrogen generation rate through the encapsulation and degradation of GelMA, ultimately achieving continuous and controlled hydrogen supply and stable therapeutic effects for osteoarthritis. In vitro and in vivo experiments confirmed the safety and efficacy of this material. The results showed that the material could continuously and efficiently generate hydrogen in simulated physiological environments (100 mg of material could generate 8.6% hydrogen), effectively eliminate cellular reactive oxygen species (ROS positive rate reduced by 85.89%), reduce cellular senescence and apoptosis (cell death rate decreased by 52%, SA-βgal expression decreased by 78.3%), promote normal chondrocyte function (Col II expression increased by 67.4%, Ki67 expression increased by 87.5%), and improve osteoarthritis in rats (OARSI score increased by 216%). The in situ hydrogen generation and control system designed in this study provides a new method for the hydrogen's local and stable treatment of osteoarthritis. STATEMENT OF SIGNIFICANCE: Hydrogen (H₂) has great potential in the treatment of osteoarthritis by alleviating oxidative stress, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study introduces an innovative injectable material combining H-Si nanosheets and GelMA short fibers to address this issue. By enabling continuous in situ hydrogen generation, this material effectively eliminates reactive oxygen species, reduces oxidative stress and inflammation, and promotes tissue repair. In vitro and in vivo experiments demonstrate its high hydrogen generation efficiency, safety, and therapeutic efficacy, offering a promising new approach for osteoarthritis management.