Cytotoxicity caused by degradation products of iron biodegradable stents: Effect of Fe3+

FAGALI NS; GRILLO CA; PUNTARULO S; FERNÁNDEZ LORENZO MA

Rosario

Congreso; 8vo Congreso Latinoamericano de Órganos Artificiales, Biomateriales e Ingeniería de Tejidos (COLAOB); 2014

Sociedad Latinoamericana de Biomateriales y Órganos Artificiales (SLABO)

Pure Fe and some of its alloys have been proposed for the manufacture of temporary biodegradable stents because they are susceptible to a fast corrosion in biological media. However, the release of Fe ions during dissolution may cause side effects like oxidative stress and inflammation in the tissues in contact with the implant. Both, the relevance of these processes and the mechanisms by which these deleterious effects are produced, have not been sufficiently described in the literature. In this paper, the effect of Fe3+ ions and pH changes on CHO-K1 cell cultures was assessed. To evaluate the ?Fe effect?, CHO-K1 cells were exposed to culture medium (CM) supplemented with different amounts of Fe3+ salt (FeCl3.6H2O, 1-5 mM). The ?pH effect? was determined using CM adjusted to pH values similar to those reached after the addition of Fe salt. Mitochondrial activity (MTT technique), oxidative damage to lipids (thiobarbituric reactive substance generation, TBARS), soluble Fe in CM and intracellular Fe (spectrophotometric method) were determined. For both treatments assayed (either ?Fe effect? or ?pH effect?) the cellular mitochondrial activity was lower than the control. The decrease in mitochondrial activity in the 1-2 mM range Fe3+ was only due to the decrease in pH. Conversely, the effect of Fe in the 3 to 4 mM range was greater than that caused by the pH itself. In the presence of Fe species, higher oxidative damage was found than in control cells. Importantly, TBARS production did not depend on pH changes. Intracellular Fe content was higher than in control cells in the 3-4 mM range; however, in this concentration range, soluble Fe in CM decreased as Fe level increased. Results indicate that cytotoxicity depends on pH changes (at 1-5 mM Fe added range) and intracellular Fe content (at 3-4 mM Fe added range), while oxidative damage is only observed in the presence of Fe. The higher concentration of intracellular Fe, with lower soluble Fe content in CM at 3-4 mM range, could be explained assuming that during precipitation some soluble Fe complexes are washed away by insoluble species that may be endocyted by the cells. Under this condition, viability of cells decreases. The changes, occurring at the interface biomaterial/biological medium during the degradation of Fe, may markedly affect the viability of cells in the vicinity of the Fe-based implant.