The two faces of titanium dioxide nanoparticles bio-camouflage in 3D bone spheroids

Abstract

Titanium (Ti) and its alloys are widely used in dental implants and hip-prostheses due to their excellent biocompatibility. Growing evidence support that surface degradation due to corrosion and wear processes, contribute to implant failure, since the release of metallic ions and wear particles generate local tissue reactions (peri-implant inflammatory reactions). The generated ions and wear debris (particles at the micron and nanoscale) stay, in a first moment, at the interface implant-bone. However, depending on their size, they can enter blood circulation possibly contributing to systemic reactions and toxicities. Most of the nanotoxicological studies with titanium dioxide nanoparticles (TiO 2 NPs) use conventional two-dimensional cell culture monolayers to explore macrophage and monocyte activation, where limited information regarding bone cells is available. Recently three-dimensional models have been gaining prominence since they present a greater anatomical and physiological relevance. Taking this into consideration, in this work we developed a human osteoblast-like spheroid model, which closely mimics bone cell-cell interactions, providing a more realistic scenario for nanotoxicological studies. The treatment of spheroids with different concentrations of TiO 2 NPs during 72 h did not change their viability significantly. Though, higher concentrations of TiO 2 NPs influenced osteoblast cell cycle without interfering in their ability to differentiate and mineralize. For higher concentration of TiO 2 NPs, collagen deposition and pro-inflammatory cytokine, chemokine and growth factor secretion (involved in osteolysis and bone homeostasis) increased. These results raise the possible use of this model in nanotoxicological studies of osseointegrated devices and demonstrate a possible therapeutic potential of this TiO 2 NPs to prevent or reverse bone resorption.

<p>Involvement of TGF-β and ROS in G1 Cell Cycle Arrest Induced by Titanium Dioxide Nanoparticles Under UVA Irradiation in a 3D Spheroid Model</p>

“…In accordance with our results, no significant differences in spheroid proliferation was seen in osteoblast spheroids cultured in agarose following exposure to nano-TiO 2 . 16 The formation of smaller colonies following treatment with nano-TiO 2 under UVA irradiation suggested a lower proliferation rate as compared with the control, nano-TiO 2 , and UVA groups; therefore, the number of cells in the 3D spheroids was counted, verifying that larger colonies contained more cells due to a higher proliferation rate.…”

“…Three-dimensional (3D) culture models are a promising alternative, since they provide cell−cell and cell−matrix interactions that better mimic the physiological in vivo aspects. [15][16][17] Human osteoblast-like spheroids treated with nano-TiO 2 have been shown to augment collagen deposition and proinflammatory cytokine and growth factor secretion, although no significant differences in morphology, proliferation, or cell cycle have been observed. 16 Nevertheless, the molecular mechanisms underlying the osteoblast spheroid alterations caused by nano-TiO 2 are not well understood.…”

Cytotoxic effects of submicron- and nano-scale titanium debris released from dental implants: an integrative review

“…The role of the proteins is creating an initial nano-bio interface that undergoes dynamic alterations as particles traffics onto or into cells [30]. Previous studies showed that metallic particles released from dental implants can accumulate in the surrounding tissues [9,65], or even spread systemically, as reported in previous studies [66,67], contributing to the chronic inflammatory state in peri-implant diseases [68,69].…”

Evaluando la toxicidad de nanomateriales en modelos celulares tridimensionales

“…En ese sentido, se presentan reportes en los cuales se describe la evaluación de NPs de metales y óxidos en estos sistemas tridimensionales. Se ha evaluado el efecto citotóxico y la capacidad de internalización de nanopartículas de dióxido de titanio (NPs TiO 2 ) en cultivos celulares de osteoblastos humanos para estudiar las respuestas de la interacción célula-célula en el tejido óseo (Souza et al, 2019). Los resultados de esa investigación demostraron que después de 72 horas de exposición a las NPs TiO 2 , la viabilidad celular no se afectó.…”

“…Sin embargo, la incubación de los esferoides de osteoblastos con concentraciones elevadas de NPs TiO 2 , influenciaron su ciclo celular permitiendo su diferenciación y mineralización. Un hallazgo importante es que las concentraciones elevadas de NPs TiO 2 indujeron la expresión de citosinas pro-inflamatorias y factores de crecimiento involucrados en la homeostasis del hueso y la osteólisis (Souza et al, 2019). En otro estudio, se evaluó la eficacia de la terapia fotodinámica utilizando NPs de TiO 2 en células de glioma cultivadas en esferoides, los resultados muestran una disminución significativa de la viabilidad celular en las primeras 6 horas post-tratamiento inducida por la radiación con luz UV (Yamaguchi et al, 2010).…”