title: The molecular mechanism for effects of TiN coating on NiTi alloy on endothelial cell function.
abstract: The aim of this study is to systematically investigate the molecular mechanism of different effects of nickel titanium (NiTi) alloy surface and titanium nitride (TiN) coating on endothelial cell function. Release of nickel (Ni) ion from bare and TiN-coated NiTi alloys and proliferation of endothelial cells on the two materials were evaluated, and then influence of the two materials on cellular protein expression profiles was investigated by proteomic technology. Subsequently, proteomic data were analyzed with bioinformatics analyses and further validated using a series of biological experiments. Results showed that although the two materials did not affect cell proliferation, the Ni ions released from bare NiTi alloy generated inhibition on pathways associated with actin cytoskeleton, focal adhesion, energy metabolism, inflammation, and amino acid metabolism. In comparison, TiN coating not only effectively prevented release of Ni ions from NiTi alloy, but also promoted actin cytoskeleton and focal adhesion formation, increased energy metabolism, enhanced regulation of inflammation, and promoted amino acid metabolism. Furthermore, the two processes, "the initial mediation of adsorbed serum protein layer to endothelial cell adhesion and growth on the two materials" from our previous study, and "the following action of the two materials on cellular protein expression profile", were linked up and comprehensively analyzed. It was found that in stage of cell adhesion (within 4 h), release of Ni ions from bare NiTi alloy was very low, and the activation of adsorbed proteins to cell adhesion and growth related biological pathways (such as regulation of actin cytoskeleton, and focal adhesion pathways) was almost as same as TiN-coated NiTi alloy. This indicated that the released Ni ions did not affect the mediation of adsorbed proteins to endothelial cell adhesion. However, in stage of cell growth and proliferation, the release of Ni ions from bare NiTi alloy increased with time and reached a higher level, which inhibited endothelial cell function at molecular level, whereas TiN coating improved endothelial cell function.
authors.affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Dayun
authors.initials: D
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China. Electronic address: luxy@seu.edu.cn.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lü
authors.affiliation: Nanjing Drum Tower Hospital, Nanjing 210008, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Shenzhen Research Institute, Peking University, Shenzhen 518055, PR China.
authors.forename: Tingfei
authors.initials: T
authors.lastname: Xi
authors.affiliation: R&D Center of Lifetech Scientific (Shenzhen) Co., Ltd, Shenzhen 518057, PR China.
authors.forename: Deyuan
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000327:Adsorption; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D019295:Computational Biology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007477:Ions; D009532:Nickel / Q000032:analysis / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects; D014025:Titanium / Q000494:pharmacology*
chemical_list: D020099:Coated Materials, Biocompatible; D007477:Ions; C040654:titanium nickelide; D016753:Interleukin-10; D009569:Nitric Oxide; C041500:titanium nitride; D009532:Nickel; D000255:Adenosine Triphosphate; D014025:Titanium
keywords: Biomaterials–cell interactions; Molecular mechanism; NiTi alloy; Proteomics and bioinformatics; Titanium nitride coating