疏水疏油纳米银镀膜冠状动脉支架的研究
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摘要
目的:在316L不锈钢材料表面制备纳米结构,改善316L不锈钢表面疏水、疏油性能,观察银纳米镀层对血液相容性及细胞相容性的影响,并在316L不锈钢冠脉支架表面制备银纳米镀层,利用动物实验探讨其在生物体内抗支架内血栓及支架内再狭窄的能力,为冠状动脉支架表面改性研究提供依据。
     方法:本研究采用恒电位电沉积的方法在316L不锈钢表面沉积银纳米镀层,并将钢板置于全氟硅烷溶液中浸泡,达到改变钢板表面微观形貌,改善钢板疏水、疏油性能的目的。电镜及红外光谱检测均证实银纳米涂层成功沉积在316L不锈钢表面,且测试疏水角、疏油角和表面银纳米颗粒直径。通过动态凝血实验、抗凝血时间测定、血小板粘附实验、溶血实验、蛋白吸附实验等手段,测试银镀膜全氟硅烷浸泡316L不锈钢的血液相容性。并通过细胞粘附实验、MTT法及流式细胞仪检测细胞周期的方法测试细胞相容性。将银镀膜全氟硅烷浸泡316L不锈钢具有不同疏水疏油性能的冠脉支架置入兔腹主动脉内,通过比较置入时和1个月后的造影及血管内超声结果,并对比病理切片结果,判断体内环境下,纳米结构及疏水疏油性能改变对内皮化、血栓形成及再狭窄的影响。
     结果:316L不锈钢利用恒电位电沉积法进行表面沉积银纳米镀层,并以全氟硅烷浸泡后,具备了一定的微相粗糙度,并改善了疏水、疏油性能,血液相容性的很多指标较裸钢板明显改善。比如血小板粘附数量、激活程度、白蛋白吸附量,而抗凝血性能、溶血率及纤维蛋白吸附量至少不次于裸钢板。其中,800s和1600s电镀处理组的抗凝血性能及抗血小板吸附激活能力好于2000s及4000s组。细胞粘附试验,各组全氟硅烷浸泡银纳米镀层疏水、疏油性能改善钢板结果明显好于裸钢板,MTT与流式细胞仪检测显示,疏水、疏油性能改善对细胞相容性无明显影响。动物实验部分,疏水疏油性能改善的316L不锈钢制成的支架置入动物体内后较裸支架不增加置入当时及1个月时血栓发生率,支架具有良好的组织相容性,在支架周围组织没有明显的炎症反应,各组全氟硅烷浸泡的纳米银镀膜316L不锈钢支架内膜厚度都较裸支架薄,内膜面积较裸支架小,其中800s,1600s,4000s均有显著统计学意义(P<0.05);而中膜厚度、中膜面积,800s,1600s,2000s较裸支架薄,具有统计学意义(P<0.05),4000s与裸支架类似;管腔面积方面,各组之间无统计学意义的差别,但是800s,1600s,2000s组较裸支架组增大。
     结论:在316L不锈钢表面进行银镀膜并在氟化硅烷中浸泡后,可以形成表面纳米结构,可改善316L不锈钢的疏水疏油性能,并具有良好地血液相容性及细胞相容性。银镀膜全氟硅烷浸泡316L不锈钢支架不影响急性或亚急性血栓形成,并可以加速血管内皮化过程,减少支架内再狭窄的发生。
Coronary artery stent is breakthrough of coronary heart disease treatment intwenty century, saved a lot of patients, but so far, stent is not so perfect, thebiggest two problems are stent thrombosis and in-stent restenosis. Good bloodcompatibility and cell compatibility is the precondition of solving the twoproblems above, what’s more,we need to find a balance betweenendothelialization and inhibition of vascular smooth muscle cells proliferation.The hydrophobic performance, oleophobic property and surface nanometermicrostructure greatly influences the endothelialization and inhibition ofvascular smooth muscle cells proliferation.There are few researchs abouthydrophobic and oleophobic property’s effects on blood compatibility and cellcompatibility.There is no reports about using nanotecnology to improve316lstainless steel stents’ hydrophobic performance and oleophobic property orverifying performance of stents through animal experiments. In this research,Ag nanoparticles films were prepared by electrodeposition,The thin films werethen treated with a avantin solution of1H,1H,2H,2H–Perfluorooctyltriethoxysilane (0.25v/v) for20h. After these solution,316L stainless steel’ssurface mircoscopic view changed, so we succeed to improve thehydrophobicity and oleophobic property, this paper discusses how thenanoscale microstructure and the change of the hydrophobic and oleophobicperformance improve the performance of coronary stents. It may provide areference to the new coronary stents research in the future.
     In this research, Ag nanoparticles films were prepared byelectrodeposition,The thin films were then treated with a avantin solution of1H,1H,2H,2H–Perfluorooctyl triethoxysilane (0.25v/v) for20h. After thesesolution,316L stainless steel’s surface mircoscopic view changed, so wesucceed to improve the hydrophobicity and oleophobic property. Both electronmicroscopy (sem) and infrared spectrum detection confirmed Ag nanoparticleshad already successfully deposited on the316l stainless steel surface, Different depositing time makes different diameters of Ag nanoparticles,between90to130nm. The hydrophobicity contact Angle is between130to143°higher than60°of bare steel,the oleophobic contact Angle is between between66to76°higher than0°of bare steel. By dynamic blood coagulation experiment,Anticoagulant time measurement, Platelet adhesion experiment, hemolysis test,Protein adsorption experiment, we test the blood compatibility effect of thefilms. Cell compatibility is tested by cell adhesion experiment, MTT and flowcytometry detection. Ag nanoparticles coating316l stainless steel stents’ bloodcompatibility is obviously improved compared with bare steel,such as thenumber of platelet adhesion, activation degree, albumin adsorption, andanticoagulation. Indicators, hemolysis rate and fiber protein adsorption, are atleast not inferior to bare steel. Among electrodeposition groups,800s and1600s groups’ anticoagulation property and antiplatelet performance are betterthan2000s and4000s groups. In the cell adhesion test, all Ag nanoparticlesgroups results are significantly better than bare steel, MTT and flow cytometryinstrument testing showed cell compatibility is the same with bare steel group.In vivo,we put Ag nanoparticles coronary stents in rabbit abdominal aorta,then we make an angiography and intravascular ultrasound immediately and1month later.Besides angiography and intravascular ultrasound, we contrastpathological findings to judge the nano structure and hydrophobic oleophobicperformance influence in endothelialization, thrombosis and restenosis.Compared with bare steel stent,Ag nanoparticles coronary stent supportedgood histocompatibility,doesn’t increase the incidence of thrombosis in1month, surrounding the stents,tissues have no obvious inflammation, Agnanoparticles coronary stent’s intima thickness was thinner than barestents,intima area is smaller than bare metal stents,800s,1600s,4000sgroups have obvious statistical significance (P <0.05); tunica media thicknessand area have a negative change in800s,1600s,2000s groups,have obviousstatistical significance (P<0.05),4000s groups is similar to the bare stent group.Lumen area of all groups has no obvious statistical significance.But 800s,1600s,2000s groups are larger than the other groups.
     This study shows that electrodeposition of Ag nanoparticles can formsurface nano structure on316l stainless steel, can improve the316l stainlesssteel hydrophobic and oleophobic performance, the stents with Agnanoparticles have good blood compatibility and cell compatibility,does notaffect the acute or subacute thrombosis, and can accelerate vascularendothelial process, reduce the occurrence of stent restenosis.
引文
1.Bauters C,Isner JM.The biology of restenosis[J].Progress inCardiovascular Disease,2007,40:107-116
    2.胡大一.美国心脏病学学会第54届年会热点荟萃.中华心血管病杂志.2005(06):1222-1223
    3.胡大一.WCC/ESC2006会议主题:心血管疾病和人口老龄化.中国心血管病研究杂志.2006(10):721-723)
    4.Tersteeg C, Roest M, Mak-Nienhuis EM, Ligtenberg E, Hoefer IE, de GrootPG, Pasterkamp G. A fibronectin-fibrinogen-tropoelastin coating reducessmooth muscle cell growth but improves endothelial cell function.[J]Cell Mol Med.2012Jan6:1582-4934.
    5.Fernandez RA,Garcia EJ,Vargas F,et al.Effects of chronicincreased salt intake on nitric oxide synthesis inhibition inducedhypertension[J].Hypertens,2005,13:123-128.
    6.Faloon BJ,Heagerty AM.In vitroperfusion study of human resistenceartery function in essential hypertersion[J].Hypertens,2004,24:14-33.
    7.Moreuo PD,Uscuo LV,Shaw S,et al.Angiotensin II increase tissueendothelin and induces vascular hypertrophy:reversal by ETreceptor antagonist[J].Circulation,1997,96:593.
    8.Tepe G, Schmehl J, Wendel H P, et al. Reduced thrombo-genicity ofnitinol stents—In vitro evaluation of differentsurface modificationsand coatings [J]. Biomaterials,2006,27:643
    9.Pache J, Kastrati A, Mehilli J, et a1. Intracoronary stenting andangiographic results: strut thickness effect on restenosisoutcome(ISAR-STEREO-2) trial. J Am Coll Cardiol2003;41(8):1283-1288],
    10. Chen M C, Liang H F, Sung H W, et al. A novel drug-elu-ting stentspray-coated with multi-layers of collagen and sirolimus [J]. J ControlRelease,2005,108:178
    11.Leon MB, Abizaid A, Moses JW. Subgroup analysis from the Cypherclinical trial The CYPHER Stent: A New Gold Standard in the Treatmentof Coronary Artery Disease [C].New York: Cardiovascular ResearchFoundation,2003:54-57.
    12.Ellis SG, Colombo A, Grube E, et al. Incidence, timing, and correlatesof stent thrombosis with the polymeric paclitaxel drug-eluting stent-A TAXUS II, IV, V, and VI meta-analysis of3,445patients followed forup to3years [J]. J Am Coll Cardiol,2007,49:10431051
    13.Tamai H, Igaki K, Kyo E, et al. Initial and6-month results ofbiodegradable poly-L-lactic coronary stents in humans [J]. Circulation,2000,102:399;
    14.Lincoff A M, Furst J G, Ellis S G, et al. Sustained local deliveryof dexamethasone by a novel intravascular eluting stent to preventrestenosis in the porcine coronary injury model [J]. J Am Coll Cardiol,1997,29:808;
    15. Venkatraman S, Poh T L, Vinalia T, et al. Collapse pressures ofbiodegradable stents [J]. Biomaterials,2003,24:2105
    16.V. Subramanian,W.J. van Ooij. Siane Based Metal Pretreatment asAlternatives to Chromating [J]. Surface Engineering,1999,15(20):168~172.
    17.徐溢,王楠,棣铭熙.钢铁表面防腐硅烷膜表面处理新技术【J】.重庆大学学报:自然科学版,2001,24(2):135—136.
    18. Subramanian V, Vanooji WJ. Silane based metal pretreatments asalternatives to chromating [J]. Surface Engineering,1999,15(2):125.
    19.Child T, Vanooji WJ. Application of silane technology to preventcorrosion of metals and improve paint adhesion [J]. Trans IMF,1999,77(2):64-70.
    20.Harun M K, Lyon SB, Marsh J. A surface analytical study offunctionalized mild steel for adhesion promotion of organic coatings.Prog Org Coat,2003,46:21.
    21.Hansal W E, Hansal S. Investigation of polysiloxane coatings ascorrosion inhibitors of zinc surfaces. S urf Coat Technol,2006,200:3056.
    22.Khramov A N, Balbyshev V N, Voevodin N N. Nanostructured solgelderived conversion coatings based on epoxy2and aminosilanes. Prog OrgCoat,2003,47:207.
    23. Feng X. J., Feng, L., Jin, M. H., Zhai, J., Jiang L. and Zhu D. B.,Reversible Super-hydrophobicity to Super-hydrophilicity Transition ofAligned ZnO Nanorod Films. J. AM. CHEM. SOC.2004,126,62-63
    24.江雷.从自然到仿生的超疏水纳米界面材料[J].化工进展.2003(12)
    25.曲爱兰;文秀芳;皮丕辉;程江;杨卓如超疏水涂膜的研究进展化学进展2006(10)
    26.段辉,白晨,汪厚植,赵雷,赵慧中氟树脂/硅溶胶复合涂层的制备和超疏水性能研究化工新型材料2006(07)
    27.冯琳,江雷超疏水性纳米界面材料的制备与研究(英文)基础科学2005(01)
    28.FENG L,LI S H,LI Y S,et al.Super-hydrophobic surfaces:from naturalto artificial[J].Advanced Materials,2002,14(24):1857-1860.
    29.Sun TL,Feng L,Gao X F,Jiang L Bioinspired surfaces with specialwettability. Acc Chem Res,2005,38:644-652
    30.WENZEL R N.Resistance of solid surfaces to wettingbywater[J].Industrial and Engineering Chemistry,1936,28(8):988-994
    31.Cassie A B D, Baxter S. Wettability of porous surfaces [J]. TransFaraday Soc,1944,40:546-551.
    32.任露泉,王淑杰,周长海,赵维福.典型植物非光滑疏水表面的理想模型[J].吉林大学学报(工学版),2006,36(增刊2):97-102
    33.郑黎俊,乌学东,楼增,吴旦.表面微细结构制备超疏水表面[J]科学通报.200449(17):1691-1699
    34. Wu J,Mate C M.Langmuir,1998,14:4929~4939
    35. Fukushima H,Seki S,Nishikawa T,Takiguchi H Combinatorialbiosynthesis of legume natural and rare triterpenoids in engineeredyeast. Plant Cell Physiol.2013,Jan31
    36.Nishino T, Meguro M, Nakamae K, et al. The lowest surface free energybased on-CF3alignment[J]. Langmuir,1999,15:4321-4323
    37.Blossey R.Self-cleaning surfaces-virtual realities.NatureMaterials,2003,2,301-306
    38. Neinhuis C, Barthlott W. Characterization and distribution ofwater-repellent, self-cleaning plant surfaces[J]. Annals of Botany,1997,79:667-677
    39.Feng X. J., Feng, L., Jin, M. H., Zhai, J., Jiang L. and Zhu D. B.,Reversible Super-hydrophobicity to Super-hydrophilicity Transition ofAligned ZnO Nanorod Films. J. AM. CHEM. SOC.2004,126,62-63
    40.Meng, H. F., Wang, S. T., Xi, J. M., Tang, Z. Y., Jiang, L.. FacileMeans of Preparing Superamphiphobic Surfaces on Common EngineeringMetals. J. Phys. Chem. C2008,112,11454–11458.
    41.GB/T16886.1-2001医疗器械生物学评价第1部分:评价与试验
    42.Baszkin A,Lyman D.Formation and characterization of an ultrathinpolysiloxane film onto mica[J]. Biomed. Mater Res,1988,126(2):629-633.43Ito Y.,Kajihara M, Imanishi Y.Cell growth on immobilized cell-growthfactor: II.Adhesion and growth of fibroblast cells on poly(methylmethacrylate) membrane immolilized with proteins of variouskinds[J].Biomed. Mater. Res,1991,13(11):789-794,
    44.Altankov G., Thom V., GRoth T., et al. Modulation the biocompatilityof polymer surgaces with poly(ethylene glycol): Effect fibronection[J].J Biomen Mater Ress,2000,52:219-230
    45.Pakalns T., L. Haverstick K, Fields GB., et al. Cellular recognitionof synthetic peptide amphiphiles in self-assembled monolayer filmsimplications for a collagen structural modulation mechanism of tumorcell invasion[J].Biomaterials1999,20:2265
    46.Walsh F.S., Doherty P. Cell adhesion molecules and neuronalregeneration[J]。 Current Opinion in Cell Biology,1996,8:707.
    47.林思聪。高分子生物材料分子工程研究进展(上)【J】.高分子通报,1997,(1):1-7.
    48王冰利用表面张力组成理论研究高分子膜对蛋白质的吸附作用,东北林业大学硕士毕业论文,2010
    49沈阳NiTi合金表面微观形貌对血管内皮细胞及血小板黏附的影响稀有金属与材料2010,6(39)1018-1021
    50Poon VK, Burd A.In vitro cytotoxity of silver:implication forclinical wound care[J]. Burns.2004,30:140-147P
    51Bosetti M,Cannas M. Silver coated materials for external fixationdevices; in ivtrobiocompatibility and genotoxicity[J]. Biomaterials.2002,23;887-892P
    52王建中,姜晓峰等实验诊断学第二章出血与血栓性疾病的实验诊断第二节凝血因子的检测。
    53张兴栋.生物材料的发展动态和趋势.新材料产业,2000,(12):78~81
    54Chen J Y, Wan G J, Leng J X, et al. Behavior of cultured human umbilicalvein endothelial cells on titanium oxide films fabricated by plasmaimmersion ion implantation and deposition. Surface&CoatingsTechnology,2004,(186):270-276
    55汪钟,郑植荃主编.现代血栓病学.北京:北京医科大学中国协和医科大学联合出版社,1997.
    56Chaturvedi S, Yadav JS. The role of antiplatelet therapy in carotidstenting for ischemic stroke prevention. Stroke.2006;37(6):1572-1577.
    57崔福斋,冯庆玲.生物材料学.第2版.清华大学出版社.2011:10-200
    58李伯刚,那娟娟,尹光福,殷杰,郑昌琼.生物碳素材料表面血小板黏附的实验研究生物医学工程学杂志.2004,21(1):12-15
    59Ko TM, Lin JC, Cooper SL. Surface characterization and platelectadhesion studies of plasma-sulphonated polyethylene. Biomaterials.1993,14(9):657-664
    60易树,尹光福,郑昌琼.生物材料表面界面特性与其血液相容性的关系.中国口腔种植学杂志.2003,8(2):83-88
    61俞耀庭,张兴栋.生物医用材料.天津大学出版社.2000
    62Frazier. The development,evolution,and clinical utilization ofartificial heart technology.European Journal of Cardio-thoracic Surgery,11suppl.1997, S29-S31
    63Munro M. S., Quatt rone A. J., Ell sw orth S. R. et al.. T rans. Am. S oc. Art if. Int ern. Organs.[J],1981,27:499—503
    64白蛋白原位复合的生物医用功能材料的研究(Ⅱ)——白蛋白的选择性吸附和血液相容性研究高等学校化学学报2002年12月2369~2374
    65表面微米拓扑结构的构建及对血小板和内皮细胞的影响郭祥2009年西南交通大
    [66]Didier Falconneta, Gabor Csucsb, H. Michelle Grandina, Marcus Texto.Surface engineering approaches to micropattern surfaces for cell-basedassays.Biomaterials.2006,27;3044-3063
    67崔福斋,冯庆玲.生物材料学.第2版.清华大学出版社.2011:10-200
    68Rausch-fan X, Qu Z, Wieland M, et al. Differentiation andcytokine synthesis of human alveolar osteoblasts compared toosteoblast-like cells (MG63) inresponse to titanium surfaces[J].Dent Mater,2008,24(1):102-110.
    [69] Ismail FS, Rohanizadeh R, Atwa S, et al. The influence of surfacechemistry and topography on the contact guidance of MG63os-teoblast cells[J]. J Mater Sci Mater Me,2007,18(5):705-714.
    70孙敏杨华啸周平潘銮凤刘水聚羟基脂肪酸酯的亲水性改性及其与人脐静脉内皮细胞相容性的研究《高分子学报》2010年12期
    71Dalby MJ, Childs S, Riehle MO,et al. Fibroblast rection to islandtopography: changes in cytoskeleton and morphology with time.Biomaterials,2003;24(6)∶927
    72Dalby MJ, Giannaras D, Riehle MO,et al. Rapid fibroblast adhesion to27nm high polymer demixed nano-topography. Biomaterials,2004;25(1)∶77
    73Curtis AS, Gadegaard N, Dalby MJ,et al. Cells react to nanoscale orderand symmetry in their surroundings. IEEE Trans Nanobioscience,2004;3(1)∶61
    74Gallagher JO, Mcghee KF, Wilkinson CDW,et al. Interaction of animalcells with ordered nano-topography. IEEE Trans Nanobioscience,2002;3(1)∶24
    75Biological evaluation of medical devices--Part4:Selection of testsfor interactions with blood. China Standards Press2003-08-01
    76Poon VK, Burd A.In vitro cytotoxity of silver:implication for clinicalwound care[J]. Burns.2004,30:140-147P
    77Bosetti M,Cannas M. Silver coated materials for external fixationdevices; in ivtrobiocompatibility and genotoxicity[J]. Biomaterials.2002,23;887-892P
    78.Gutensohn K, Beythien C, Bau J, et al. In vitro analyses of diamondlike carbon coated stents: reduction of metal ion release, p lateletactivation, and rombogenicity. Thrombosis Research,2000;99∶577
    79Starosvetsky D, Gotman I. T iN coating improves the corrosion behaviorof superelastic N iT i surgical alloys. Surface and Coatings Techno logy,2001;148
    80Amon M, Bo lzA, Heublein B, et al. Coating of cardiovascular stentsw ith amorphous silicion carbide to reduce thrombogenicity. IEEE,1994
    81JonesM I, M cCo ll IR, Grant DM, et al. Haemocompatibility of DLCand T iC-T iN Interlayers on titanium. D imond and RelatedM aterials,1999;8∶457
    82Child T, Vanooji WJ. Application of silane technology to preventcorrosion of metals and improve paint adhesion [J]. Trans IMF,1999,77(2):64-70.
    83Godin B, Sakamoto JH, Serda RE, Grattoni A, Bouamrani A, Ferrari M.Emerging applications of nanomedicine for the diagnosis and treatmentof cardiovascular diseases. Trends in Pharmacological Sciences,2010,31,199-205.
    84Price RL, Waid MC, Haberstroh KM,et al. Selective bone cell adhesionon formulations containing carbon nanofibers.Biomaterials,2003;24(11)∶1877
    85Kunzler TP,Huwiler C,Drobek T,et al. Systematic study of osteoblastresponse to nanotopography by means of nanoparticle-density gradients[J]. Biomaterials,2007,28(33):5000-5006.
    86. Webster TJ, Ejiofor JU. Increased osteoblast adhesion onnanophasemetals: Ti,Ti6Al4V,and CoCrMo [J]. Biomaterials,2004,25(19):4731-4739.
    87.Li B,Logan BE. Bacterial adhesion to glass and metal-oxide surfaces[J]. Colloids Surf B Biointerfaces,2004,36(2):81-90.
    88.de Oliveira PT,Zalzal SF,Beloti MM,et al. Enhancement of in vitroosteogenesis on titanium by chemically produced nanotopogra-phy[J]. JBiomed Mater Res A,2007,80(3):554-564.
    89. Gentile F,Tirinato L,Battista E,et al. Cells preferentially growon rough substrates[J]. Biomaterials,2010,31(28):7205-7212.
    90. Dalby M,Riehle M,Johnstone H,et al.Polymer-demixed nanotopography:control of fibroblast spreading and proliferation[J]. Tis-sue Eng,2002,8(6):1099-1108.
    91.NiTi合金表面微观形貌对血管内皮细胞及血小板黏附的影响稀有金属与材料2010,6(39)1018-1021
    92. Theis T, et al. nanotechnology n. Nat Nanotechnol.2006;1(1):8–10.
    93. Riehemann K, et al. Nanomedicine--challenge and perspectives. AngewChem Int Ed Engl.2009;48(5):872–897.
    94. Kong DF, Goldschmidt-Clermont PJ. Tiny solutions for giant cardiacproblems. Trends Cardiovasc Med.2005;15(6):207–211.
    95. Pan D, et al. Sensitive and efficient detection of thrombus withfibrin-specific manganese nanocolloids. Chem Commun (Camb)2009;(22):3234–2346.
    96. Pan D, et al. Ligand-directed nanobialys as theranostic agent fordrug delivery and manganese-based magnetic resonance imaging of vasculartargets. J Am Chem Soc.2008;130(29):9186–9197.
    97.Michalet X, et al. Quantum dots for live cells, in vivo imaging, anddiagnostics. Science.2005;307(5709):538–544.
    98. Devaraj NK, et al.18F labeled nanoparticles for in vivo PET-CTimaging. Bioconjug Chem.2009;20(2):397–401.
    99. Nahrendorf M, et al. Nanoparticle PET-CT imaging of macrophages ininflammatory atherosclerosis. Circulation.2008;117(3):379–87.
    100. Devaraj NK, et al.18F labeled nanoparticles for in vivo PET-CTimaging. Bioconjug Chem.2009;20(2):397–401.
    101. Nahrendorf M, et al. Nanoparticle PET-CT imaging of macrophages ininflammatory atherosclerosis. Circulation.2008;117(3):379–87.
    102. Kao CY, et al. Long-residence-time nano-scale liposomal iohexol forX-ray-based blood pool imaging. Acad Radiol.2003;10(5):475–83.
    103. Mukundan S, Jr., et al. A liposomal nanoscale contrast agent forpreclinical CT in mice. AJR Am J Roentgenol.2006;186(2):300–7.
    104. Brito L, Amiji M. Nanoparticulate carriers for the treatment ofcoronary restenosis. Int J Nanomedicine.2007;2(2):143–61.
    105. Buxton DB. Nanomedicine for the management of lung and blooddiseases. Nanomed.2009;4(3):331–9.
    106. Lanza GM, et al. Nanomedicine opportunities for cardiovasculardisease with perfluorocarbon nanoparticles. Nanomed.2006;1(3):321–9.
    107. Winter PM, et al. Antiangiogenic synergism of integrin-targetedfumagillin nanoparticles and atorvastatin in atherosclerosis. JACCCardiovasc Imaging.2008;1(5):624–634.
    108. Winter PM, et al. Endothelial alpha(v)beta3integrin-targetedfumagillin nanoparticles inhibit angiogenesis in atherosclerosis.Arterioscler Thromb Vasc Biol.2006;26(9):2103–20129.
    109. Marsh JN, et al. Fibrin-targeted perfluorocarbon nanoparticles fortargeted thrombolysis. Nanomed.2007;2(4):533–543.
    110. Vasan RS. Biomarkers of cardiovascular disease: molecular basis andpractical considerations. Circulation.2006;113(19):2335–2362.
    111. Danesh J, et al. C-reactive protein and other circulating markersof inflammation in the prediction of coronary heart disease. N Engl JMed.2004;350(14):1387–1397.
    112. Wang TJ, et al. Plasma natriuretic peptide levels and the risk ofcardiovascular events and death. N Engl J Med.2004;350(7):655–663.
    113. Danesh J, et al. Plasma fibrinogen level and the risk of majorcardiovascular diseases and nonvascular mortality: an individualparticipant meta-analysis. JAMA.2005;294(14):1799–1809.
    114. Cushman M, et al. Fibrinolytic activation markers predictmyocardial infarction in the elderly. The Cardiovascular Health Study.Arterioscler Thromb Vasc Biol.1999;19(3):493–498.
    115. Mangoni AA, Jackson SH. Homocysteine and cardiovascular disease:current evidence and future prospects. Am J Med.2002;112(7):556–565.
    116. Wang TJ, et al. Multiple biomarkers for the prediction of firstmajor cardiovascular events and death. N Engl JMed.2006;355(25):2631–9.
    117. Gaspari M, et al. Nanoporous surfaces as harvesting agents for massspectrometric analysis of peptides in human plasma. J Proteome Res.2006;5(5):1261–1271
    118. Luchini A, et al. Smart hydrogel particles: biomarker harvesting:one-step affinity purification, size exclusion, and protection againstdegradation. Nano Lett.2008;8(1):350–361.
    119. Cui Y, et al. Nanowire nanosensors for highly sensitive andselective detection of biological and chemical species. Science.2001;293(5533):1289–1292.
    120. McKendry R, et al. Multiple label-free biodetection andquantitative DNA-binding assays on a nanomechanical cantilever array.Proc Natl Acad Sci U S A.2002;99(15):9783–8.
    121. Hoffmann R, et al. Patterns and mechanisms of in-stent restenosis.A serial intravascular ultrasound study. Circulation.1996;94(6):1247–54.
    122. Samaroo HD, Lu J, Webster TJ. Enhanced endothelial cell density onNiTi surfaces with sub-micron to nanometer roughness. Int J Nanomedicine.2008;3(1):75–82.
    123. Lagerqvist B, et al. Long-term outcomes with drug-eluting stentsversus bare-metal stents in Sweden. N Engl J Med.2007;356(10):1009–1012.
    124. Mauri L, et al. Stent thrombosis in randomized clinical trials ofdrug-eluting stents. N Engl J Med.2007;356(10):1020–1029.
    125. Stone GW, et al. Safety and efficacy of sirolimus-andpaclitaxel-eluting coronary stents. N Engl J Med.2007;356(10):998–1008.
    126. Wieneke H, et al. Synergistic effects of a novel nanoporous stentcoating and tacrolimus on intima proliferation in rabbits. CatheterCardiovasc Interv.2003;60(3):399–407.
    127. Bhargava B, et al. A novel paclitaxel-eluting porous carbon-carbonnanoparticle coated, nonpolymeric cobalt-chromium stent: evaluation ina porcine model. Catheter Cardiovasc Interv.2006;67(5):698–702.
    128. Erlebacher J, et al. Evolution of nanoporosity in dealloying. Nature.2001;410(6827):450–453.
    129. Ayon AA, et al. Drug loading of nanoporous TiO2films. Biomed Mater.2006;1(4):11–15.
    130. Liu DM, Yang Q, Troczynski T. Sol-gel hydroxyapatite coatings onstainless steel substrates. Biomaterials.2002;23(3):691–698.
    131. Caves JM, Chaikof EL. The evolving impact of microfabrication andnanotechnology on stent design. J Vasc Surg.2006;44(6):1363–1368.

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