Tantalum Particles Promote M2 Macrophage Polarization and Regulate Local Bone Metabolism via Macrophage-Derived Exosomes Influencing the Fates of BMSCs

In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (M phi) polarization, Ta particles regulating calcium signaling pathways and promoting M2 M phi polarization. Ta-induced M2 M phi enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous M phi polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate M phi polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 M phi, providing insights for potential bone repair applications. Tantalum (Ta) particles enhance M2 macrophage (M phi) polarization via regulating calcium signaling pathways. Ta-induced M2 M phi promote proliferation, migration, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) through exosomal delivery of miR-378a-3p/miR-221-5p and the downregulation of miR-155-5p/miR-212-5p. Additionally, Ta particles mitigate the pro-inflammatory and bone resorption effects of titanium (Ti) particles, accelerating bone defect repair. image