The TiO ₂ -μ implant residual is more toxic than the Al ₂ O ₃ -n implant residual via blocking LAP and inducing macrophage polarization

Medical device residuals cause harmful effects and diseases in the human body, such as Particle Disease (PD), but the biological interaction of different types of particles is unclear. In this study, after a biological interaction screen between different particles, we aimed to explore the mechanism of the biological interaction between different types of particles, and the effect of a proteasome inhibitor on PD. Our studies showed that the titanium oxide microscale particle (Ti-μ) was more toxic than the aluminum oxide nanoscale particle (Al-n). Al-n activated LAP, attenuated the macrophage M1 polarization, inhibited the activator of the NF-κB pathway, and blocked the secretion of inflammatory factors and apoptosis in vitro, and also prevented the inflammation tissue disorder and aseptic loosening in vivo induced by Ti-μ. What is more, Bortezomib blocked apoptosis, secretion of inflammatory factors and the activation of the NF-κB pathway induced by TiO2 micro particles. Al-n-induced autophagy could play the function in the efficient clearance of dying cells by phagocytosis, and serves in dampening M1 polarization-related pro-inflammatory responses. While the Ti alloy medical implant and devices are applied worldwide, the toxicity of Ti-μ and its interaction with Al-n could be considered in the implant design, and Bortezomib was a potential therapeutic for PD.