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

Excessive production of reactive oxygen species (ROS) amplifies pro-inflammatory pathways and exacer-bates immune responses, and is a key factor in the progression of osteoarthritis (OA). Therapeutic hy-drogen gas (H 2 ) with antioxidative and anti-inflammatory effects, has a potential for OA alleviation, but the targeted delivery and sustained release of H 2 are still challenging. Herein, we develop an injectable calcium boride nanosheets (CBN) loaded hydrogel platform (CBN@GelDA hydrogel) as a high-payload and sustainable H 2 precursor for OA treatment. The CBN@GelDA hydrogel could maintain constant physio-logical pH conditions which further promotes more H 2 release than the CBN alone and lasts more than one week. The biocompatibility of this hydrogel with macrophages and chondrocytes is effectively en-hanced. 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 pheno-type, 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 H 2-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 H 2 precursor calcium boride nanosheet (CBN), which is the first to use as an H 2 precursor, integrates superior injectable and biocompatible of hydrogel and the se-lection of antioxidant properties of H 2 . This system can improve H 2 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.(c) 2022 Published by Elsevier Ltd on behalf of Acta Materialia Inc.