Host–device interactions: exposure of lung epithelial cells and fibroblasts to nickel, titanium, or nitinol affect proliferation, reactive oxygen species production, and cellular signaling

Abstract

Endoscopic implantation of medical devices for the treatment of lung diseases, including airway stents, unidirectional valves and coils, is readily used to treat central airway disease and emphysema. However, granulation and fibrotic tissue formation impairs treatment effectiveness. To date little is known about the interaction between implanted devices, often made from metals, such as nickel, titanium or nitinol, and cells in the airways. Here, we study the response of lung epithelial cells and fibroblasts to implant device materials. The adhesion and proliferation of bronchial epithelial cells and lung fibroblasts upon exposure to 10 × 3 × 1 mm pieces of nickel, titanium or nitinol is examined using light and scanning electron microscopy. Pro-inflammatory cytokine mRNA expression and release, signaling kinase activity and intracellular free radical production are assessed. Nitinol, and to a lesser extent nickel and titanium, surfaces support the attachment and growth of lung epithelial cells. Nitinol induces a rapid and significant alteration of kinase activity. Cells directly exposed to nickel or titanium produce free radicals, but those exposed to nitinol do not. The response of lung epithelial cells and fibroblasts depends on the metal type to which they are exposed. Nitinol induces cellular surface growth and the induction of kinase activity, while exposure of lung epithelial cells to nickel and titanium induces free radical production, but nitinol does not. Graphical Abstract

Corrosion Behavior of Nickel–Titanium Continuous-Casted Alloys

“…The results of our study are in agreement with recently reported evidence that human lung fibroblasts displayed altered cell signaling when indirectly exposed to nitinol alloys [39]. The Ni 2+ ions released from the alloy increased free radical production in cells, suggesting metal toxicity.…”

What is the impact of plastic deformation on cytocompatibility of biodegradable Zn–Mg alloys?

“…In biomaterial studies, T1 relaxometry has also been used to reveal whether free radicals are generated in lung epithelial cells exposed to nickel, titanium, and nitinol. 15 It is worth mentioning that T1 relaxometry has already shown great potential in monitoring the free radical generation during e.g. , chemical reactions, 16 shear stress in endothelial cells, 17 response of bacteria to antibiotics, 18 or upon viral infections.…”

“…, chemical reactions, 16 shear stress in endothelial cells, 17 response of bacteria to antibiotics, 18 or upon viral infections. 19 The versatility of the technique has been demonstrated while detecting free radicals in various cell cultures, including the already-mentioned epithelial 15 and endothelial 17 cells, as well as dendritic cells, 20 HeLa cells, 21 macrophages, 22 granulosa cells, 23 or sperm cells. 24 The method enables measurements in single-cell organelles, such as mitochondria, 25 or particular cellular locations, such as acrosomes.…”