Enhanced Osteolysis Targeted Therapy through Fusion of Exosomes Derived from M2 Macrophages and Bone Marrow Mesenchymal Stem Cells: Modulating Macrophage Polarization

Abstract Aseptic loosening of prostheses is a highly researched topic, and wear particle‐induced macrophage polarization is a significant cause of peri‐prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs‐Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2‐Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2‐Exos and BMSCs‐Exos fused exosomes (M2‐BMSCs‐Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2‐BMSCs‐Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2‐BMSCs‐Exos can be used as a precise and reliable molecular drug for peri‐prosthetic osteolysis. Fused exosomes M2‐BMSCs‐Exos were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes.