Differential inflammatory macrophage response to rutile and titanium particles

Titanium and its alloys are widely used as implant materials for dental and orthopaedic applications due to their advantageous bulk mechanical properties and biocompatibility, compared to other metallic biomaterials. In order to improve their wear and corrosion resistance, several surface modifications that give rise to an outer ceramic layer of rutile have been developed. The ability of rutile wear debris to stimulate the release of inflammatory cytokines from macrophages has not been addressed to date. We have compared the in vitro biocompatibility of sub-cytotoxic doses of rutile and titanium particles in THP-1 cells driven to the monocyte/macrophage differentiation pathway as well as in primary cultures of human macrophages. Confocal microscopy experiments indicated that differentiated THP-1 cells and primary macrophages efficiently internalised rutile and titanium particles. Treatment of THP-1 cells with rutile particles stimulated the release of TNF-alpha, IL-6 and IL-1beta to a lesser extent than titanium. The influence of osteoblasts on the particle-induced stimulation of TNF-alpha and IL-1beta was analysed by co-culturing differentiated THP-1 cells with human primary osteoblasts. Under these conditions, secretion levels of both cytokines after treatment of THP-1 cells with rutile particles were lower than after exposure to titanium. Finally, we observed that primary macrophages released higher amounts of TNF-alpha, IL-6 and IL-1beta after incubation with titanium particles than with rutile. Taken together, these data indicate that rutile particles are less bioreactive than titanium particles and, therefore, a higher biocompatibility of titanium-based implants modified with an outer surface layer of rutile is expected.