A pH-responsive injectable hydrogel that modulates the inflammatory microenvironment for the treatment of osteoarthritis.

Osteoarthritis (OA) is a widespread chronic degenerative joint disease, for which new treatment strategies are urgently needed. In this study, we developed an injectable, pH-responsive hydrogel (HA-TA-CS) aimed at improving joint drug delivery by enhancing retention within the joint cavity, while exhibiting excellent biocompatibility. The hydrogel was loaded with celecoxib for localized, in situ release (HA-TA-CS@Cel). OA is characterized by elevated levels of reactive oxygen species (ROS), which promote oxidative stress, inflammatory cytokine production, and further exacerbate the inflammatory response. HA-TA-CS@Cel effectively mitigates inflammation by scavenging excess ROS through the sustained release of TA and celecoxib. Our results demonstrate that HA-TA-CS@Cel significantly alleviates OA progression. In a mouse OA model, the system reduced pro-inflammatory factors and alleviated disease severity. Furthermore, HA-TA-CS@Cel promoted the polarization of macrophages from the M1 to the M2 phenotype, suggesting its ability to modulate the immune microenvironment and thereby attenuate joint inflammation and slow OA progression. These findings indicate that the injectable HA-TA-CS@Cel hydrogel system holds great promise for treating OA through enhanced cartilage protection and macrophage polarization, with potential applications in other inflammatory diseases.