Hyaluronic Acid Microplates for Intra-articular Lubrication and Cartilage Protection in Post-traumatic Osteoarthritis

Osteoarthritis (OA) is the most common joint disorder, characterized by a vicious cycle of synovial inflammation and cartilage degradation. Intra-articular injection of hyaluronic acid (HA)-based products, one of the currently available treatments, provides only temporary symptomatic relief without addressing the underlying inflammation. Here, we engineered several configurations of 20 × 5 μm square-shaped HA-based hydrogel microparticles (μHA) by photopolymerizing HA-methacrylate chains within a sacrificial template. The μHA mechano-pharmacological properties were tuned by adjusting the HA concentration, molecular weight, and degree of methacrylation, resulting in microparticles with a Young's modulus ranging from a few tens (30 kPa) to a few hundred (200 kPa) kilopascals; a structure stable for over a month under oxidative stress conditions; and reduced friction in simulated synovial fluids. Under H₂O₂-induced oxidative conditions, μHA decreased the production of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) in human chondrocytes to basal levels. In a three-dimensional OA cartilage model, μHA reduced glycosaminoglycan release and matrix metalloproteinase-13 activity, demonstrating chondroprotective effects. In a rigorous murine model of early-stage post-traumatic OA, a single intra-articular injection of μHA lowered proinflammatory gene expression in the synovium to basal levels. In summary, μHA offers a drug-free approach to managing OA by enhancing lubrication and reducing inflammation, providing a sustained therapeutic activity over several weeks.