The unique regulation of implant surface nanostructure on macrophages M1 polarization.

The inflammatory response is the first and inevitable event after implant surgery in vivo, in which the macrophages M1 polarization is mediated. Numerous publications indicate that the physical properties of implant surface nanostructure can influence macrophages M1 polarization status, whereas the regulation mechanisms have not been elucidated yet. Unlike the conventional biochemical factors that can directly bind to the cellular surface receptors or be transported into cytoplasm, the physical information of implant surface nanostructure can only be sensed by direct contact with cells. Therefore, we infer that the implant surface nanostructure may have unique regulation mechanisms. In this study, we compared the influences of the titanium implant surface coated with titania nanotubes on the surface (∼100 nm diameter, NT-100) and the standard IFN-γ/LPS stimulation on the macrophages M1 polarization. Both the NT-100 surface and IFN-γ/LPS stimulation could induce macrophages M1 polarization, indicated by significant upregulation of M1-specific molecules including CD86, iNOS, CCR7 and IL-1β, without affecting the M2-specific molecules including CD206, Arg1 and IL-10. However, we found that the IFN-γ/LPS induced macrophages M1 polarization was mediated by RBP-J-IRF8 pathway, whereas the NT-100 surface was more related to FAK-MAPKs pathway, particularly the JNK and ERK1/2 signaling. Our study demonstrated that the implant surface nanostructure has great potential to trigger the host inflammatory response through distinct pathways from conventional biochemical factors, which may remind us to re-consider the unique regulation mechanisms of nano surface on cell functions. Our finding offers a theoretical basis for titanium implant modification to benefit tissue integration.