Multifunctional Magnetic Nanoparticles For Microenvironment Modulation In Temporomandibular Joint Osteoarthritis

This study aimed to develop a multifunctional magnetic nanoparticle system to address the limitations of current temporomandibular joint osteoarthritis (TMJOA) therapies, which focus solely on cartilage biology and fail to modulate the arthritic microenvironment holistically. A γ-Fe₂O₃-based magnetic nanoparticle (γ-Fe₂O₃@TA@ALN MNPs) was engineered by integrating tannic acid (TA) and alendronate sodium (ALN). The nanoparticles were evaluated for pH-responsive decomposition, magnetic responsiveness, and biocompatibility. In vitro studies assessed their effects on chondrocyte proliferation, cartilage-specific protein synthesis, lubrication enhancement, reactive oxygen species (ROS) suppression, and catabolic gene expression. A TMJOA mouse model was established to evaluate short- and long-term therapeutic outcomes following intra-articular nanoparticle injection under a 0.2 T static magnetic field. γ-Fe₂O₃@TA@ALN MNPs demonstrated pH-sensitive ALN release in acidic environments and magnetic field-enhanced cartilage-specific protein synthesis. In vitro, they promoted chondrocyte proliferation, anisotropic organization, lubrication, and ROS reduction. Magnetic stimulation further suppressed catabolic gene expression. In vivo, nanoparticle administration significantly mitigated cartilage degeneration and subchondral bone loss in TMJOA mice, with sustained therapeutic effects observed over time. The γ-Fe₂O₃@TA@ALN MNPs effectively reconstructed the arthritic microenvironment by synergistically modulating cellular responses and inorganic components. Their magnetic responsiveness and pH-triggered drug release offer a promising strategy for TMJOA treatment, addressing both cartilage and microenvironmental pathology to improve therapeutic outcomes.