An “All‐in‐One” Strategy to Reconstruct Temporomandibular Joint Osteoarthritic Microenvironment Using γ‐Fe₂O₃@TA@ALN Nanoparticles

Abstract Current clinical strategies for the treatment of temporomandibular joint osteoarthritis (TMJOA) primarily target cartilage biology, overlooking the synergetic effect of various cells and inorganic components in shaping the arthritic microenvironment, thereby impeding the effectiveness of existing therapeutic options for TMJOA. Here, γ‐Fe₂O₃@TA@ALN magnetic nanoparticles (γ‐Fe₂O₃@TA@ALN MNPs) composed of γ‐Fe₂O₃, tannic acid (TA), and alendronate sodium (ALN) are engineered to reconstruct the osteoarthritic microenvironment and mitigate TMJOA progression. γ‐Fe₂O₃@TA@ALN MNPs can promote chondrocytes’ proliferation, facilitate chondrogenesis and anisotropic organization, enhance lubrication and reduce cartilage wear, and encourage cell movement. Magnetic‐responsive γ‐Fe₂O₃@TA@ALN MNPs also exhibit pH sensitivity, which undergoes decomposition within acidic environment to release ALN on demand. Under a 0.2 T static magnetic field, γ‐Fe₂O₃@TA@ALN MNPs accelerate the synthesis of cartilage‐specific proteins, and suppress catabolic‐related genes expression and reactive oxygen species generation, affording additional protection to TMJ cartilage. In TMJOA mouse models, articular injection of γ‐Fe₂O₃@TA@ALN MNPs effectively alleviates cartilage degeneration and subchondral bone loss in short and long terms, offering promising avenues for the development of therapeutic interventions for TMJOA.