An injectable reactive oxygen species-responsive self-assembled hydrogel loaded with L-glutamine targets cartilage repair for treatment of osteoarthritis

Osteoarthritis (OA) is closely related to articular cartilage injury and joint inflammation. L-Glutamine (L-Gln) plays a significant role in delaying articular cartilage degeneration and reducing inflammation. However, the molecular weight of L-Gln is small and its half-life in vivo is relatively short, which limits its therapeutic effect. In this study, gelatin microspheres coated with L-Gln (L-Gln@GMs) were combined with a quaternized chitosan-polyvinyl alcohol self-assembled hydrogel to prepare a composite hydrogel (L-Gln@GMs@QCSFP) that responds to an inflammatory microenvironment. The hydrogel has good mechanical properties and injectability and can be adsorbed onto the cartilage surface to respond to a high reactive oxygen species environment, thus realizing the slow and stable release of L-Gln. In in vitro experiments, the L-Gln@GMs@QCSFP hydrogel exhibited good antibacterial properties and biocompatibility, and effectively ameliorated the chondrocyte damage induced by interleukin (IL)-1β by inhibiting the IL-17 and PI3K/Akt signaling pathways. In addition, L-Gln@GMs@QCSFP also promoted polarization of macrophages from M1 type to M2 type. In an OA rat model, the L-Gln@GMs@QCSFP hydrogel also effectively delayed cartilage injury and improved synovitis. This approach is expected to provide an effective and safe new strategy for the treatment of OA.