title: Rare earth metals used in biodegradable magnesium-based stents do not interfere with proliferation of smooth muscle cells but do induce the upregulation of inflammatory genes.
abstract: Rare earth metals are added to corrodible magnesium-based alloys in low amounts (up to 10%) to improve their mechanical properties and to decrease the degradation rate. Cerium (Ce), neodymium (Nd), yttrium (Y), and ytterbium (Yb) are already used for degradable cardiovascular stents. Little is known about the biocompatibility of rare earth metals released during the degradation process of the implant. Therefore the biocompatibility of rare earth metals was assessed with regard to metabolic activity of human vascular smooth muscle cells (SMCs). After coincubation with the trivalent chlorides (0.5-100 microg/mL) of rare earth metals for 24, 72, 144, and 240 h metabolic activity was determined at each time point using the colometric WST-1 test. The tested rare earth metals did not lead to significant changes in metabolic activity over a wide concentration range. However, at high concentrations a decrease was observed. Apoptotic or necrotic effects were not observed. Furthermore, we analyzed the effects of Ce, Nd, Y, and Yb on the expression of genes involved in inflammatory processes. The expression of IL-6, IL-8, and ICAM-1 in SMCs after exposure to Ce, Nd, Y, and Yb (5 and 50 microg/mL) was measured using quantitative real-time PCR. Significant up-regulation of IL-6, IL-8, and ICAM-1 genes were only found after 24 h, mainly for a concentration of 50 microg/mL. Our cell culture data indicate that rare earth metals influence cellular processes of vascular cells. Whether adverse effects occur also in in vivo is the topic of further investigations.
authors.affiliation: Department of Pediatric Cardiology and Intensive Care, Children's Hospital, University of Rostock, Rembrandtstrasse 16/17, Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Drynda
authors.forename: Nicole
authors.initials: N
authors.lastname: Deinet
authors.forename: Nicole
authors.initials: N
authors.lastname: Braun
authors.forename: Matthias
authors.initials: M
authors.lastname: Peuster
mesh_terms: D020341:Absorbable Implants; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008274:Magnesium; D008674:Metals, Rare Earth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015607:Stents; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D008674:Metals, Rare Earth; D018799:Intercellular Adhesion Molecule-1; D008274:Magnesium