Involvement of Decorin-Mediated Mitochondrial Quality Control in Macrophage Polarization Induced by Titania Nanotube Arrays

Macrophage polarization critically shapes the local immune microenvironment during bone implant osseointegration and can be modulated by implant surface nanotopography. Unfortunately, the underlying mechanisms still need to be elucidated. Previously our group has confirmed the macrophage polarization rules on titania nanotube arrays (NT) with different diameters. In the present study, we wonder whether mitochondria are involved, considering their significant role in macrophage polarization. The NT surface with a larger diameter (∼100 nm) could induce M1 polarization, accompanied by more active mitochondrial fission and depolarization, as indicated by increased mitochondrial number, reactive oxygen species (ROS) generation, mtDNA/nDNA ratio, and reduced JC-1 aggregation. Further RNA-sequencing revealed the selective upregulation of decorin on nanotube surfaces with larger diameters, and macrophage M1 polarization was diminished after decorin downregulation. As a versatile extracellular matrix molecule, decorin bridges the gap between implant surface nanotopography and mitochondria responses. These findings reveal a mitochondria-centered mechanism whereby implant nanoarchitecture directs immune responses, providing a novel target for designing immunomodulatory biomaterials.