Intra-articular injection of platinum nanozyme-loaded silk fibroin/pullulan hydrogels relieves osteoarthritis through ROS scavenging and ferroptosis suppression

Reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of osteoarthritis (OA). Consequently, it is speculated that anti-ferroptosis agents could represent a novel therapeutic strategy for managing OA. In this study, a hydrogel incorporating platinum (Pt) nanozyme was synthesized by dispersing Pt nanoparticles (NPs) within a matrix of silk fibroin (SF) and oxidized pullulan (oxPL). This hydrogel allows for a substantial and sustained release of up to 30 days. The gelation time (from 140.3 ± 42.3 s to 460.0 ± 40.0 s), swelling capacity (from 57.7 ± 3.8 % to 24.0 ± 7.0 %), and degradation rate (from 60.3 ± 4.7 % to 32.0 ± 4.6 %) of the hydrogels can be modulated by adjusting the Pt NP content. The Pt@SF/oxPL hydrogel effectively eliminates ROS due to its catalase-like and superoxide dismutase-like enzymatic properties. In vitro studies demonstrated that Pt@SF/oxPL efficiently mitigated the process of ferroptotic cell death in chondrocytes. More critically, intra-articular administration of Pt@SF/oxPL showcased therapeutic advantages by both protecting and stimulating the regeneration of cartilage throughout the progression of OA. Collectively, this study suggests that Pt@SF/oxPL hydrogels could potentially serve as an effective treatment for OA, presenting a novel nanozyme-based therapeutic approach for this condition.