title: Nickel ions inhibit α-actin expression and decrease aspect ratio of rat vascular smooth muscle cells in vitro.
abstract: Traditionally, in vitro material biocompatibility studies involved evaluating cell response when cultured in the presence of a sample of the material. In this study, we present a different approach to evaluate the biocompatibility of a metallic biomaterial. Our study is based on estimating what local concentrations of metallic ions are present at the site of implantation of an endovascular stent based on other studies in the literature. We then quantify the concentrations of metallic ions present in our conditioned media in which Nitinol wires were allowed to corrode, and compare cell response to ion concentrations in order to provide better experimental reproducibility. This is important to eliminate the variability of ion release rates from metals (even from the same lot) under similar conditions. Cell culture experiments using vascular smooth muscle cells exposed to clinically significant concentrations of nickel ions released from Nitinol showed two important responses. A decrease in cell aspect ratios showing a morphological change possibly indicating a shift towards a more synthetic phenotype was observed. Secondly, a decrease in α-actin expression was characterized by immunostaining with a fluorescent tag. At the highest concentration tested, average fluorescence decreased by approximately 26%, indicating a loss of the cellular contractile mechanism. However, the ion concentrations utilized in this study did not significantly affect cellular proliferation.
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, South Carolina, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Winn
authors.forename: C Derrick
authors.initials: CD
authors.lastname: Quarles
authors.forename: R Kenneth
authors.initials: RK
authors.lastname: Marcus
authors.forename: Martine
authors.initials: M
authors.lastname: LaBerge
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D000497:Alloys; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016014:Linear Models; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D014025:Titanium
chemical_list: D000199:Actins; D000497:Alloys; C013616:nitinol; D009532:Nickel; D014025:Titanium