In vivo assessment of TiO 2  based wear nanoparticles in periprosthetic tissues

A multimodal approach combining inductively coupled plasma mass spectrometry (ICP-MS), single-particle ICP-MS (spICP-MS), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDS) and Raman spectroscopy enabled a deeper insight into the balance between total titanium (Ti), the soluble titanium fraction and titanium dioxide based particle fraction levels in periprosthetic tissues collected from patients undergoing revision surgery. Hydrofluoric acid usage in the sample digestion allowed for complete digestion of TiO particles, thus enabling accurate estimation of total Ti levels. The TiO fraction represents 38-94% of the titanium load in the six samples where particles were detected, and the fraction is present mainly in samples from patients with aseptically loosened total hip arthroplasty. Further attention was given to this fraction determining the elemental composition, particle count, particle size and modification of TiO . The spICP-MS analysis confirmed the presence of the TiO -derived (nano)particles (NPs) with a 39- to 187-nm median size and particle count up to 2.3 × 10 particles per gram of tissue. On top of that, the SEM-EDS confirmed the presence of the TiO nanoparticles with 230-nm median size and an anatase crystal phase was determined by Raman spectroscopy. This study presents a novel multimodal approach for TiO particle determination and characterization in tissue samples and is the first in vivo study of this character.