Macrophage-targeted, ROS-removing and H₂S-releasing nanomicelle encapsulated in hydrogel microspheres for the treatment of osteoarthritis

The progression and severity of osteoarthritis (OA) are significantly associated with intra-articular synovitis, with the imbalance of M1/M2 macrophages serving as a critical driving factor in the pathogenesis of synovitis. In this study, we developed macrophage-targeted nanomicelles capable of scavenging reactive oxygen species (ROS) and releasing hydrogen sulfide (H₂S). These nanomicelles were encapsulated within injectable methacrylate gelatin (GelMA) porous hydrogel microspheres, thereby creating a new H₂S gas therapy platform for the treatment of osteoarthritis. In vitro experiments demonstrated that GelMA@FPLBD actively targeted macrophages, efficiently removed ROS, and gradually released H₂S. This process inhibited the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in activated macrophages, thereby suppressing M1 polarization and promoting M2 polarization, resulting in significant anti-inflammatory effects. In vivo experiments utilizing a destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) rat model further revealed the anti-inflammatory and cartilage-protective properties of GelMA@FPLBD, effectively mitigating the progression of OA. Therefore, this study indicates that GelMA@FPLBD, functioning as a H₂S gas therapy platform, holds significant promise for the treatment of osteoarthritis (OA).