Injectable spontaneous hydrogen-releasing hydrogel for long-lasting alleviation of osteoarthritis

Excessive production of reactive oxygen species (ROS) amplifies pro-inflammatory pathways and exacerbates immune responses, and is a key factor in the progression of osteoarthritis (OA). Therapeutic hydrogen gas (H₂) with antioxidative and anti-inflammatory effects, has a potential for OA alleviation, but the targeted delivery and sustained release of H₂ are still challenging. Herein, we develop an injectable calcium boride nanosheets (CBN) loaded hydrogel platform (CBN@GelDA hydrogel) as a high-payload and sustainable H₂ precursor for OA treatment. The CBN@GelDA hydrogel could maintain constant physiological pH conditions which further promotes more H₂ release than the CBN alone and lasts more than one week. The biocompatibility of this hydrogel with macrophages and chondrocytes is effectively enhanced. The experiments show that the CBN@GelDA hydrogel holds the ROS scavenging ability, reducing the expression of related inflammatory cytokines, lessening M1 macrophages but stimulating M2 phenotype, and thereby decreasing chondrocyte apoptosis, which facilitates to breaking of the vicious circle of OA progression. Furthermore, a single-time injection of the CBN@GelDA hydrogel markedly reduces joint destruction in OA rats. From what has been discussed above, this injectable spontaneous H₂-releasing hydrogel is promising for OA treatment. STATEMENT OF SIGNIFICANCE: Oxidative stress and inflammation play the key role in the occurrence and development of osteoarthritis (OA). The system of a hydrogel loaded with H₂ precursor calcium boride nanosheet (CBN), which is the first to use as an H₂ precursor, integrates superior injectable and biocompatible of hydrogel and the selection of antioxidant properties of H₂. This system can improve H₂ release behavior and achieve a single injection into the articular cavity to alleviate the progression of OA in rats. This study of the combination of a convenient long-acting injectable hydrogel and a safe therapeutic gas is of great value for improving the quality of life of clinical patients.