The Effects of Cu-doped TiO2 Thin Films on Hyperplasia, Inflammation and Bacteria Infection

In the present work, different concentrations of Cu ion (1, 2, 5 and 10 wt %) were doped in the TiO2 film by a sol-gel method and dip coating process. The morphology of the Cu-doped TiO2 films were characterized by scanning electron microscopy (SEM) and the results showed that the doped Cu made no change to the TiO2 films. The nitric oxide (NO) release experiment showed that these Cu-doped surfaces showed the ability of catalytic decomposition of exogenous donor S-nitroso-N-acetyl-penicillamine (SNAP) to generate (NO). Based on fluorescence analysis and CCK-8 quantitative results, such films had the ability to inhibit smooth muscle cells adhesion, proliferation and migration with SNAP in vitro. The macrophage adhesion assay and anti-bacterial test proved that such Cu-doped TiO2 films also possessed anti-inflammatory and anti-bacterial abilities. All the abilities above showed positive correlation with the amounts of the doped Cu. This study suggested that the Cu-doped TiO2 films were capable of generating physiological levels of NO in the presence of endogenous donor S-nitrosothiols (RSNO), endowing the TiO2 films with anti-hyperplasia, anti-inflammatory and anti-bacterial abilities.

[1]  R. Dixon,et al.  Nitric oxide functions as a signal in plant disease resistance , 1998, Nature.

[2]  David D Roberts,et al.  Nitric oxide in wound‐healing , 2005, Microsurgery.

[3]  Nan Huang,et al.  In vitro investigation of enhanced hemocompatibility and endothelial cell proliferation associated with quinone-rich polydopamine coating. , 2013, ACS applied materials & interfaces.

[4]  David B Matchar,et al.  Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. , 2007, JAMA.

[5]  Ping Yang,et al.  Fabrication of 3D TiO2 micromesh on silicon surface and its effects on platelet adhesion , 2014 .

[6]  George Broughton,et al.  The Basic Science of Wound Healing , 2006, Plastic and reconstructive surgery.

[7]  Ping Yang,et al.  Effect of micropatterned TiO2 nanotubes thin film on the deposition of endothelial extracellular matrix: For the purpose of enhancing surface biocompatibility. , 2015, Biointerphases.

[8]  Patrick Hunziker,et al.  Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. , 2006, Journal of the American College of Cardiology.

[9]  Kun Zhang,et al.  A novel coculture model of HUVECs and HUASMCs by hyaluronic acid micropattern on titanium surface. , 2014, Journal of biomedical materials research. Part A.

[10]  Claudio Napoli,et al.  Nutrition, physical activity, and cardiovascular disease: an update. , 2007, Cardiovascular research.

[11]  David E Newby,et al.  Preserved endothelial vasomotion and fibrinolytic function in patients with acute stent thrombosis or in-stent restenosis. , 2003, Thrombosis research.

[12]  Davide Ferrari,et al.  Microvascular inflammation in atherosclerosis , 2014 .

[13]  In-Kyu Park,et al.  Suppression of post-angioplasty restenosis with an Akt1 siRNA-embedded coronary stent in a rabbit model. , 2012, Biomaterials.

[14]  D. Lyn H. Williams The Chemistry of S-Nitrosothiols , 1999 .

[15]  O. Akhavan,et al.  Lasting antibacterial activities of Ag-TiO2/Ag/a-TiO2 nanocomposite thin film photocatalysts under solar light irradiation. , 2009, Journal of colloid and interface science.

[16]  Andreas E May,et al.  Antiplatelet therapy after coronary stenting: for how long? , 2013, The Lancet.

[17]  N. A. Scott,et al.  Restenosis following implantation of bare metal coronary stents: pathophysiology and pathways involved in the vascular response to injury. , 2006, Advanced drug delivery reviews.

[18]  C. A. Trombly,et al.  Occupational Therapy for Physical Dysfunction , 1989 .

[19]  Ping Yang,et al.  Preparation and characterization of Cu-doped TiO2 thin films and effects on platelet adhesion , 2015 .

[20]  M. Okada,et al.  A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells. , 2012, Biochemical and biophysical research communications.

[21]  A. Barbul,et al.  Nitric Oxide and Wound Healing , 2004, World Journal of Surgery.

[22]  Zhaohua Cai,et al.  Moving with and beyond CANTOS: How to put out the fire of inflammation in atherosclerosis? , 2015, International journal of cardiology.

[23]  Omid Akhavan,et al.  Photocatalytic Reduction of Graphene Oxide Nanosheets on TiO2 Thin Film for Photoinactivation of Bacteria in Solar Light Irradiation , 2009 .

[24]  David F. Williams On the mechanisms of biocompatibility. , 2008, Biomaterials.

[25]  Paul H. A. Quax,et al.  Restenosis after PCI. Part 2: prevention and therapy , 2012, Nature Reviews Cardiology.

[26]  Ping Yang,et al.  Fabrication of micro-patterned titanium dioxide nanotubes thin film and its biocompatibility , 2014 .

[27]  Kun Zhang,et al.  Preparation of SiO2/TiO2 and TiO2/TiO2 micropattern and their effects on platelet adhesion and endothelial cell regulation , 2013 .

[28]  Howard C Tenenbaum,et al.  Clinical efficacy of antibiotics in the treatment of peri-implantitis. , 2013, International dental journal.

[29]  Christopher Rensing,et al.  Metallic Copper as an Antimicrobial Surface , 2010, Applied and Environmental Microbiology.

[30]  Ping Yang,et al.  The effect of coimmobilizing heparin and fibronectin on titanium on hemocompatibility and endothelialization. , 2011, Biomaterials.

[31]  Katsumi Miyauchi,et al.  Circulating soluble LR11, a novel marker of smooth muscle cell proliferation, is enhanced after coronary stenting in response to vascular injury. , 2014, Atherosclerosis.

[32]  S D Bruck,et al.  New ideas in biomaterials science--a path to engineered biomaterials. , 1994, Journal of biomedical materials research.

[33]  J. Ji,et al.  Surface-mediated functional gene delivery: an effective strategy for enhancing competitiveness of endothelial cells over smooth muscle cells. , 2013, Biomaterials.

[34]  Jeong-Woo Choi,et al.  Surface plasmon resonance immunosensor for the detection of Salmonella typhimurium. , 2004, Biosensors & bioelectronics.

[35]  A. Mombelli,et al.  Microbiology and antimicrobial therapy of peri-implantitis. , 2002, Periodontology 2000.

[36]  Y. Vodovotz,et al.  Superoxide Modulates the Oxidation and Nitrosation of Thiols by Nitric Oxide-derived Reactive Intermediates , 1997, The Journal of Biological Chemistry.

[37]  Ulrike Diebold,et al.  The surface science of titanium dioxide , 2003 .

[38]  Mary Cushman,et al.  Associations of the beta-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis. , 2007, Thrombosis research.

[39]  M. Mittelman,et al.  Coronary stent bacterial infection with multiple organ septic emboli. , 2005, European journal of internal medicine.

[40]  D. L. Williams,et al.  Generation of nitric oxide from S-nitrosothiols using protein-bound Cu2+ sources. , 1996, Chemistry & biology.

[41]  Volker Klauss,et al.  Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. , 2010, The New England journal of medicine.

[42]  Kun Zhang,et al.  Research of smooth muscle cells response to fluid flow shear stress by hyaluronic acid micro-pattern on a titanium surface. , 2013, Experimental cell research.

[43]  Lan Huang,et al.  Transplantation of endothelial progenitor cells overexpressing endothelial nitric oxide synthase enhances inhibition of neointimal hyperplasia and restores endothelium-dependent vasodilatation. , 2011, Microvascular research.

[44]  Ping Yang,et al.  Design and construction of TiO 2 nanotubes in microarray using two-step anodic oxidation for application of cardiovascular implanted devices , 2015 .

[45]  S. Gordon Alternative activation of macrophages , 2003, Nature Reviews Immunology.

[46]  Gary L Myers,et al.  Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. , 2003, Circulation.

[47]  Omid Akhavan,et al.  Flash photo stimulation of human neural stem cells on graphene/TiO2 heterojunction for differentiation into neurons. , 2013, Nanoscale.

[48]  S. Bölükbas,et al.  Drug-eluting Stents , 2009, Der Chirurg.