title: Cytotoxicity of corrosion products of degradable Fe-based stents: relevance of pH and insoluble products.
abstract: Fe-based biodegradable metallic materials (Fe-BMMs) have been proposed for cardiovascular applications and are expected to disappear via corrosion after an appropriate period. However, in vivo studies showed that Fe ions release leads to accumulation of orange and brownish insoluble products at the biomaterial/cell interface. As an additional consequence, sharp changes in pH may affect the biocompatibility of these materials. In the present work, the experimental protocols were designed with the aim of evaluating the relative importance that these factors have on biocompatibility evaluation of BMMs. Mitochondrial activity (MTT assay) and thiobarbituric acid reactive substances (TBARS) assay on mammalian cells, exposed to 1-5 mM of added Fe3+ salt, were assessed and compared with results linked exclusively to pH effects. Soluble Fe concentration in culture medium and intracellular Fe content were also determined. The results showed that: (i) mitochondrial activity was affected by pH changes over the entire range of concentrations of added Fe3+ assayed, (ii) at the highest added Fe3+ concentrations (≥3 mM), precipitation was detected and the cells were able to incorporate the precipitate, that seems to be linked to cell damage, (iii) the extent of precipitation depends on the Fe/protein concentration ratio; and (iv) lipid peroxidation products were detected over the entire range of concentrations of added Fe3+. Hence, a new approach opens in the biocompatibility evaluation of Fe-based BMMs, since the cytotoxicity would not be solely a function of released (and soluble) ions but of the insoluble degradation product amount and the pH falling at the biomaterial/cell interface. The concentration of Fe-containing products at the interface depends on diffusional conditions in a very complex way that should be carefully analyzed in the future.
authors: Institute for Research in Theoretical and Applied Physical Chemistry (INIFTA), CONICET, Department of Chemistry, Faculty of Pure Sciences, UNLP, CC 16, Suc. 4, 1900, La Plata, Buenos Aires, Argentina.
authors: Natalia S
authors: NS
authors: Fagali
authors: Institute for Research in Theoretical and Applied Physical Chemistry (INIFTA), CONICET, Department of Chemistry, Faculty of Pure Sciences, UNLP, CC 16, Suc. 4, 1900, La Plata, Buenos Aires, Argentina.
authors: Claudia A
authors: CA
authors: Grillo
authors: Physical Chemistry - Institute of Biochemistry and Molecular Medicine (IBIMOL), School of Pharmacy and Biochemistry, UBA-CONICET, Buenos Aires, Argentina.
authors: Susana
authors: S
authors: Puntarulo
authors: Institute for Research in Theoretical and Applied Physical Chemistry (INIFTA), CONICET, Department of Chemistry, Faculty of Pure Sciences, UNLP, CC 16, Suc. 4, 1900, La Plata, Buenos Aires, Argentina; Faculty of Engineering, UNLP, 1900 La Plata, Buenos Aires, Argentina. Electronic address: mmele@inifta.unlp.edu.ar.
authors: Mónica A
authors: MA
authors: Fernández Lorenzo de Mele
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry / Q000494:pharmacology*; D003343:Corrosion; D003412:Cricetulus; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D005427:Flocculation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D010084:Oxidation-Reduction; D015607:Stents; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D002712:Chlorides; D005290:Ferric Compounds; D017392:Thiobarbituric Acid Reactive Substances; D007501:Iron; C024555:ferric chloride
keywords: Biocompatibility; Biomaterials; Cytotoxicity; Degradable; Iron