Effects of antibacterial nanostructured composite films on vascular stents: hemodynamic behaviors, microstructural characteristics, and biomechanical properties Han-Yi Cheng,1,2 Wen-Tien Hsiao,2,3,4* Li-Hsiang Lin,2,4 Ya-Ju Hsu,5 Andi Wardihan Sinrang,6 Keng-Liang Ou1,2,7,8 1
Research Center for Biomedical Implants and Microsurgery Devices, Taipei Medical University, Taipei 110, Taiwan Research Center for Biomedical Devices and Prototyping Production, Taipei Medical University, Taipei 110, Taiwan 3 Department of Diagnostic Radiology, Taipei Medical University Hospital, Taipei 110, Taiwan 4 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan 5 Department of Dentistry, Sijhih Cathay General Hospital, Taipei 221, Taiwan 6 Department of Physiology Faculty of Medicine Hasanuddin University, 90245, Makassar, Indonesia 7 Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan 8 Department of Dentistry, Taipei Medical University-Shuang Ho Hospital, Taipei 235, Taiwan 2
Received 16 September 2013; revised 21 November 2013; accepted 11 March 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35172 Abstract: The purpose of this research was to investigate stresses resulting from different thicknesses and compositions of hydrogenated Cu-incorporated diamond-like carbon (a-C:H/Cu) films at the interface between vascular stent and the artery using three-dimensional reversed finite element models (FEMs). Blood flow velocity variation in vessels with plaques was examined by angiography, and the a-C:H/Cu films were characterized by transmission electron microscopy to analyze surface morphology. FEMs were constructed using a computer-aided reverse design system, and the effects of antibacterial nanostructured composite films in the stress field were investigated. The maximum stress in the vascular stent occurred at the intersections of net-like structures. Data
analysis indicated that the stress decreased by 15% in vascular stents with antibacterial nanostructured composite films compared to the control group, and the stress decreased with increasing film thickness. The present results confirmed that antibacterial nanostructured composite films improve the biomechanical properties of vascular stents and release abnormal stress to prevent restenosis. The results of the present study offer the clinical benefit of inducing superior C 2014 Wiley Periodibiomechanical behavior in vascular stents. V cals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2014.
Key Words: 3D-reversed model, biomechanics, finite element analysis, surface treatment, vascular stent
How to cite this article: Han-Yi Cheng, Wen-Tien Hsiao, Li-Hsiang Lin, Ya-Ju Hsu, Andi Wardihan Sinrang, Keng-Liang Ou. 2014. Effects of antibacterial nanostructured composite films on vascular stents: hemodynamic behaviors, microstructural characteristics, and biomechanical properties. J Biomed Mater Res Part A 2014:00A:000–000.
INTRODUCTION
Angioplasty is accepted as a safe technique for treating myocardial infarction, coronary artery heart disease, and thrombus. Figure 1 shows magnetic resonance images (MRIs) of plaques in the neck artery before and after stenting. The clinical effects of stenting are influenced by various factors such as inadequate balloon expansion, artery injury, stent recoil, and restenosis, which is the most critical problem. In the 1980s, neointimal hyperplasia and elastic recoil were investigated extensively, and many cardiologists researched methods to eliminate these problems.1,2 Previously, neointimal hyperplasia occurred approximately
in 40% of patients within 326 months after stenting. Subsequently, a repeat of the procedure was usually performed for restenosis.3,4 Coated-surface technology is widely used in medical devices because of their outstanding biocompatibility properties. Diamond-like carbon (DLC) has been proposed for use in blood-contacting devices5–7 such as electrosurgical devices, artificial hearts, mechanical heart valves, and artery stents.8,9 Various reports have shown that the anticoagulation property of DLC is related to the bonding structure, hydrophobicity, and smooth surface.10,11 Restenosis is a common problem after stenting because of vessel
*Co-first author Correspondence to: K.-L. Ou; e-mail: [email protected] Contract grant sponsor: Department of Health, Executive Yuan, Taiwan; contract grant number: MOHW103-TDU-N-211-133001 Contract grant sponsor: International Congress of Oral Implantologists; contract grant number: A-101-057
C 2014 WILEY PERIODICALS, INC. V
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FIGURE 1. MRIs of blood flow (arrow) in the artery with plaques (a) before and (b) after stenting operation.
overloading, and platelet adhesion and activation. However, a DLC film is suitable to prevent blood clotting.12,13 Finite element analysis (FEA) is a useful tool that could be applied to quantify the biomechanical behavior in the vascular stent and surrounding arteries. FEA has been used to study the biomechanical behavior of various medical applications, including temporomandibular joint replacement, dental implants, and vascular stents under a number of loading conditions.14,15 Hydrogenated Cu-incorporated a-C:H/Cu films were prepared in the present study using a radiofrequency (RF) plasma magnetron sputtering system at various CH4/Ar gas ratios. The use of a-C:H/Cu films as promising anticoagulation and antibacterial coatings for biomedical applications was examined. The mechanical behavior at the stent–artery interface is an important factor for the clinical success of stenting; however, investigations of this behavior through experimental and theoretical analyses have thus far been scarce. To examine the biomechanical behavior of film-coated stents, the magnitude and location of the maximum stresses must be determined. Therefore, the aim of the present study was to examine the use of three-dimensional (3D) finite element models (FEMs) to quantify the maximum stresses in vascular stents with nanostructured composite films. MATERIALS AND METHODS
Angiography test Angiography is a biomedical imaging technique that is used to visualize blood vessels in the human body, such as arteries, veins, and heart chambers can be observed using contrast media. The arm vessels of six patients were selected because the vascular image of the arm is more stable than that of other parts. A special gray scale range for blood was adopted to show the regions of blood flow, and noise points could be erased. Variation in the gray scale at each moment could be used to determine the changes in blood flow. Preparation and evaluation of the a-C:H/Cu film A deposition process that combined RF plasma and a magnetron sputtering system was used to deposit the a-C:H/Cu film on a glass substratum (diameter, 1 cm; thickness, 2
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FIGURE 2. 3D FEM of the vascular stent and artery with plaques. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
mm). Various gas mixture ratios of CH4/Ar were fed into the chamber to deposit onto the films after the cleaning process.16 For deposition of the a-C:H/Cu films, nano-Cu particles were generated by sputtering a copper target (99.99% purity), which was fixed at 60 mm directly above the substratum. The microstructures of the deposited films were examined with a high-resolution transmission electron microscope (TEM, PHILIPS F-20) operated at 250 kV. 3D-reversed model analysis The 3D image models were built using the ANSYS Workbench 12.1 (ANSYS) finite element program. The vascular stents and arteries were regarded as continuous integers. Figure 2 shows a vascular stent of the standard type (Biosensors International Group; outer diameter: 3.0 mm, thickness: 0.1 mm). Clinical MRI showed that the artery had an outer diameter of 4.5 mm and a thickness of 0.5 mm, with plaques extending 5 mm and showing a central thickness of 0.5 mm. According to hyperelastic material laws, unloading follows the initial response of the stress-strain relationship, which is the rule for soft tissues in biomechanics. The balloon (diameter: 2.8 mm) was modeled in a cylindrical shape. The balloon simulated procedure was divided into two phases. The two important processes involved were converging and reinforcing of the mesh, which allow the model to approximate the actual object more accurately. Because of the deformation requirement, three types of elements were used in the present models: a 20-node solid element (Solid186) was used for the vascular stent. A fournode shell element (Shell181) was used for the balloon, and an eight-node hyperelastic element (Hyper58) was adopted in the artery. The numbers of nodes and elements were 19,852–20,412 and 12,699–13,462, respectively. The vascular stent is characterized by the properties of the 316L
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FIGURE 3. Angiography test of artery with plaques (arrow). (a) t 5 0.015 s, (b) t 5 0.020 s, (c) t 5 0.025 s, and (d) t 5 0.030 s (lift: clinical image and right: pixel image).
stainless steel. The biomechanical properties of the a-C:H/ Cu film, and tissue have been described in previous studies.17,18
In the present study, the parameters were categorized into two groups on the basis of the thickness of the coated film and the percentage of the metallic Cu element. The thicknesses of these coated films varied from 0 (control group) to 500 lm, and all models simulated with different percentages of metallic Cu element varied from 0% to 80%, for comparison. The von Mises stresses of the vascular stent and the artery were investigated in this study.
RESULTS
FIGURE 4. TEM (a) top view and (b) cross-section image of the a-C:H/ Cu film.
Figure 3 shows the blood flow velocity variation in vessels with plaques. The blood flow decreased through the narrow parts of vessels. The pixel of blood suddenly stopped increasing, and it indicated the blood was jammed because of plaques. Blood velocity decreased by >20% of the initial value. The present of plaques blocked blood flow and decreased the blood velocity, resulting in an increase in stress. To better understand the effect of Cu doping on the microstructural variation in the a-C:H film, the samples were subjected to TEM. Figure 4(a) shows the top-view image of the TEM and the corresponding selected area electron diffraction pattern (SAEDP) of the a-C:H/Cu film. Cu doping resulted in the embedding of sphere-like nanoparticles became embedded in the film. Moreover, the SAEDP consisting of ring spots revealed the presence of nanopolycrystalline structures in the film. The size and number of nano-Cu particles were proportional to the Cu content. Therefore, the production of a-C:H/ Cu films varied with the CH4/Ar ratio, and transformation of the amorphous-like phase into a nanopolycrystalline phase was induced by Cu doping/ion bombardment and radical reactions. Figure 4(b) shows a TEM cross-section image showing Cu particles embedded in the DLC film, and crystallized within molecular system. The highest stresses occurred at the intersections of the net-like structure in the vascular stent models. Figure 5
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FIGURE 5. Von Mises stress distributions of vascular stent in the (a) control group and (b) a-C:H/Cu—500:80 group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
shows the von Mises stress distribution in the vascular stent with a 500 nm a-C:H/Cu film with 80% metallic Cu element (a-C:H/Cu—500:80) and without a-C:H/Cu film (control group). The highest stress in the vascular stent of the control group was 719.22 MPa, and that in the nanostructured film group varied between 597.62 and 715.40 MPa (Fig. 6). On the other hand, the stress distribution was more uniform among the group of thicker coated films. Remarkably, the maximum von Mises stress was reduced by 16.91% in the a-C:H/Cu— 500:80 group, relative to the control group. The stress distribution showed significant stress in the untreated group. Surface treatments were shown to have the potential to decrease the abnormal stress concentration in the vascular stent. In the artery, the maximum stresses were observed at the intersections of the net-like structure of stents as shown in Figure 7. The highest stress for the artery was >10% lower in the aC:H/Cu—500:80 group than in the control group. Coated layers decreased the stresses at the interface between the vascular stent and the artery. Although no significant differences in the maximum stresses were detected between the groups with different percentages of the metallic Cu element, the maximum von Mises stress in the vascular stent and
FIGURE 6. Highest stresses of vascular stent in different thickness of a-C:H/Cu film and different percentage of metallic Cu element. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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artery was slightly smaller in the groups with a metallic Cu element than in those without. As described previously, data analysis indicated deduced stresses in vascular stents and arteries resulting from the a-C:H/Cu film, although the maximum stresses did not differ significantly between the films with and without a metallic Cu element. In our study, the maximum stress was observed at intersections of the net-like structure. Applied stress is considered one of the most important factors determining the effectiveness of vascular stents. DISCUSSION
DLC has excellent mechanical, tribological, and biological properties. The properties of DLC film can be changed within a certain range by adding other elements. We found that nano-Cu particles were embedded into the film of the samples when the a-C:H film was deposited with a Cu target under various CH4/Ar ratios. Moreover, a-C:H/Cu films were nontoxic to MG-63 and NIH-3T3 cells. Nano-Cu particles have an important role in the antibacterial mechanisms of a-C:H/Cu films. Metallic Cu elements (probably Cu1 ions or nano-Cu particles) can diffuse from the film and efficiently kill bacteria by destroying their cell walls and membranes, thereby causing their cytoplasm to leak. The a-C:H films with a Cu content have antibacterial properties against both Escherichia coli and Staphylococcus aureus. Thus, the a-C:H/ Cu film can be considered a promising antibacterial coating for applications in biomedical science and for minimally invasive surgery devices.19 Many types of image processing methods, such as grayscale discrimination, sobel filter, background subtraction, and time difference between frames are used to track and detect the contours of objectives.20–22 In the present study, the vascular structure was rebuilt by using a similar method. All the gray-scale images were executed to detect contour and noise points were eliminated by combining background subtraction method and the time difference between frames method. Vascular stents are small tube-like structures used to expand the vessel wall and restore blood flow perfusion in stenotic arteries. The stent is equipped with a balloon catheter that is delivered to the site of the plaque. As the balloon is inflated, the stent expands and is pressed against the inner vessel wall. Then, the balloon is
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FIGURE 7. Von Mises stress distributions of artery in the (a) control group and (b) a-C:H/Cu—500:80 group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
deflated and removed, and the stent remains in place to keep the vessel open. Stenting is a simpler method of solving plaque problems than traditional operations. Migliavacca et al.23 reported that stents with a lower metal-to-artery surface ratio result in a higher radial and longitudinal recoil, but a lower dogboning; the thickness also influences the stent performance in terms of recoil and dogboning. Thinner stents are associated with reduced dogboning, foreshortening, and longitudinal recoil, whereas the radial recoil is not significantly affected by the thickness. Moreover, as the slot length of the stent increases, the radial recoil increases as well. Many clinical studies have shown that the performance of vascular stents and differs stents cause different restenosis rates, which are reported to be approximately 20– 50%.24,25 Overloading may induce a greater response to injury on the vessel wall, ultimately resulting in restenosis; therefore, decreasing stress in the artery could prevent restenosis. Prendergast compared two different designs of vascular stents, the S7 (Medtronic AVE) and the NIR (Boston Scientific).26 The results of the assessment of vessel wall stresses in the stented arteries indicated that the stress to stenosis vessel was lower with the S7 stent design than with the NIR stent. These results correlated with clinical
FIGURE 8. Highest stresses of artery in different thickness of a-C:H/Cu film and different percentage of metallic Cu element. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
restenosis rates, as higher restenosis rates have been associated with the NIR design than with the S7 design. The influence of the angioplasty balloon configuration has been examined in several studies.27,28 Different typical angioplasty balloons affect the deployment of a stent to different degrees. The results of the present study indicated that balloon configuration affects the transient behavior of the vascular stent as well as the mechanical environment of the artery. The functions of vascular stents in a curved and straight vessel were compared in 2006.29 The results showed that the curved vessel model was straightened by stenting, and a hinge effect was observed at the stent. The maximum tissue prolapse of the curved vessel model was more severe than that of the straight one. The minimum lumen area of the curved vessel was decreased, compared to that of the straight vessel model. The highest stresses in the vessel were concentrated in the inner curvature of the curved vessel model, and the stress distribution of the straight vessel was similar to that of our results. FEMs are used in mechanical engineering analysis and design to evaluate potential decay. They have been successfully used in biological applications in various medical devices. In the biomedical field, models have been used to determine stresses in different biological structures, such as the facial skeleton, dental implants, and for vascular stents. Most of these FEA studies have analyzed the biomechanical behavior of individual structures or materials. However, biomechanical models of the vascular stent’s FEM are not perfect; overall, they are based on a number of assumptions and simplifications.30 An accurate comparison of our results with those obtained using FEM in previous studies is difficult because of various differences in the properties of the material, balloon expansion forces, the mesh structures, and the constrained conditions used in these models. In the present study, we considered three main materials: 316L stainless steel, a-C:H/Cu, and vessel tissue. The Young’s modulus of Cu is lower than that of DLC. Therefore, increasing the percentage of Cu will result in a softening effect on the a-C:H/Cu film to decrease stress. Moreover, the Cu element is characterized by face-centered cubic structure with many slipping planes. An increased number of Cu particles increase the slipping planes in the film. The slipping plane can be used as buffer layer to absorb stress. Therefore, the stress is decreased as the Cu particles in the film increase.
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Although the maximum stress of the stent was below the reasonable range of the 316L stainless steel material, consideration of fatigue damage was necessary because many vascular stents fail because of fatigue destruction induced by blood flow. The stresses caused by all the elements were released by the coated effect. The coated film not only contributed toward an improved biomechanical behavior, but also resulted in outstanding biocompatibility, as described in a previous study.16 Our study provided useful information on stress distribution and the most probable maximum stress locations for vascular stents. The limitations of our study are as follows: (1) we used a uniform type of vascular stent; (2) the viscoelasticity of the artery was considered; (3) the model did not include the influence of blood flow; and (4) this study was based on a theoretical analysis.
8.
9.
10.
11.
12.
CONCLUSION
Although previous studies have used FEA to examine vascular stents, few models have built stents with antibacterial nanostructured composite film. In the present study, this factor was considered important because evidence had indicated that the coated film is a critical factor for stress, and that overloading may induce a greater response to injury on the vessel wall, ultimately resulting in restenosis. Therefore, the interaction stress between the vascular stent and the artery is considered as an important factor. The aim of the present study was to understand the interface stress distribution in stenting operations. Our results indicate that vascular stents with a-C:H/Cu films may decrease overloading stress and release abnormal stress concentration to prevent restenosis. The present data suggest the clinical benefit of inducing a superior biomechanical behavior of the vascular stent.
13.
REFERENCES
18.
1. Jia H, Liu H, Kong J, Hou J, Wu J, Zhang M, Tian J, Liu H, Ma L, Hu S, Huang X, Zhang S, Zhang S, Yu B, Jang IK. A novel polymer-free paclitaxel-eluting stent with a nanoporous surface for rapid endothelialization and inhibition of intimal hyperplasia: Comparison with a polymer-based sirolimus-eluting stent and bare metal stent in a porcine model. J Biomed Mater Res Part A 2011;98A:629–637. 2. Yin T-Y, Wang G-X, Zhang D-C, Du D-Y, Li Z-G, Luo L-L, Hou Y-B, Wang Y-Z, Zhao J-B. Endothelialization and in-stent restenosis on the surface of glycoprotein IIIa monoclonal antibody eluting stent. J Biomed Mater Res Part A 2012;100A:1398–1406. 3. Stewart HJS, Guildford AL, Lawrence-Watt DJ, Santin M. Substrate-induced phenotypical change of monocytes/macrophages into myofibroblast-like cells: A new insight into the mechanism of in-stent restenosis. J Biomed Mater Res Part A 2009;90A: 465–471. 4. Indolfi L, Causa F, Giovino C, Ungaro F, Quaglia F, Netti PA. Microsphere-integrated drug-eluting stents: PLGA microsphere integration in hydrogel coating for local and prolonged delivery of hydrophilic antirestenosis agents. J Biomed Mater Res Part A 2011;97A:201–211.
15.
16.
17.
19.
20.
21.
22.
23.
24.
5. Hauert R. A review of modified DLC coatings for biological applications. Diamond Relat Mater 2003;12:583–589.
25.
6. Fedel M, Motta A, Maniglio D, Migliaresi C. Surface properties and blood compatibility of commercially available diamond-like carbon coatings for cardiovascular devices. J Biomed Mater Res Part B: Appl Biomater 2009;90B:338–349.
26.
7. Krishnan LK, Varghese N, Muraleedharan CV, Bhuvaneshwar GS, Derange`re F, Sampeur Y, Suryanarayanan R. Quantitation of pla-
6
14.
CHENG ET AL.
telet adhesion to Ti and DLC-coated Ti in vitro using 125I-labeled platelets. Biomol Eng 2002;19:251–253. Lee B, Shin H-S, Park K, Han D. Surface grafting of blood compatible zwitterionic poly(ethylene glycol) on diamond-like carboncoated stent. J Mater Sci: Mater Med 2011;22:507–514. Kim JH, Shin JH, Shin DH, Moon M-W, Park K, Kim T-H, Shin KM, Won YH, Han DK, Lee K-R. Comparison of diamond-like carboncoated nitinol stents with or without polyethylene glycol grafting and uncoated nitinol stents in a canine iliac artery model. Br J Radiol 2011;84:210–215. McLaughlin JA, Meenan B, Maguire P, Jamieson N. Properties of diamond like carbon thin film coatings on stainless steel medical guidewires. Diamond Relat Mater 1996;5:486–491. Roy RK, Lee KR. Biomedical applications of diamond-like carbon coatings: A review. J Biomed Mater Res Part B: Appl Biomater 2007;83:72–84. Yang P, Huang N, Leng YX, Chen JY, Fu RKY, Kwok SCH, Leng Y, Chu PK. Activation of platelets adhered on amorphous hydrogenated carbon (a-C:H) films synthesized by plasma immersion ion implantation-deposition (PIII-D). Biomaterials 2003;24:2821–2829. Snyder TA, Tsukui H, Kihara SI, Akimoto T, Litwak KN, Kameneva MV, Yamazaki K, Wagner WR. Preclinical biocompatibility assessment of the EVAHEART ventricular assist device: Coating comparison and platelet activation. J Biomed Mater Res Part A 2007;81A: 85–92. Cheng H-Y, Chu K-T, Shen F-C, Pan Y-N, Chou H-H, Ou K-L. Stress effect on bone remodeling and osseointegration on dental implant with novel nano/microporous surface functionalization. J Biomed Mater Res Part A 2013;101A:1158–1164. Chu K-T, Cheng H-Y, Pan Y-N, Chen S-Y, Ou K-L. Enhancement of biomechanical behavior on osseointegration of implant with SLAffinity. J Biomed Mater Res Part A 2013; 101A:1195–1200. Lee F-P, Wang D-J, Chen L-K, Kung C-M, Wu Y-C, Ou K-L, Yu C-H. Antibacterial nanostructured composite films for biomedical applications: Microstructural characteristics, biocompatibility, and antibacterial mechanisms. Biofouling 2013;29:295–305. Chung J-W, Lee C-S, Ko D-H, Han JH, Eun KY, Lee K-R. Biaxial elastic modulus of very thin diamond-like carbon (DLC) films. Diamond Relat Mater 2001;10:2069–2074. Heckmann O, Magnan H, le Fevre P, Chandesris D, Rehr JJ. Crystallographic structure of cobalt films on Cu(001): Elastic deformation to a tetragonal structure. Surf Sci 1994;312:62–72. Zhang K, Liu T, Li J-a, Chen J-y, Wang J, Huang N. Surface modification of implanted cardiovascular metal stents: From antithrombosis and antirestenosis to endothelialization. J Biomed Mater Res Part A 2013:n/a-n/a. n C, Miller M, Blomgren P. Structure enhancement diffusion Baza and contour extraction for electron tomography of mitochondria. J Struct Biol 2009;166:144–155. Bouma CJ, Niessen WJ, Zuiderveld KJ, Gussenhoven EJ, Viergever MA. Automated lumen definition from 30 MHz intravascular ultrasound images. Med Image Anal 1997;1:363–377. Pugliese F, Weustink AC, Van Mieghem C, Alberghina F, Otsuka M, Meijboom WB, van Pelt N, Mollet NR, Cademartiri F, Krestin GP, Hunink MG, de Feyter PJ. Dual source coronary computed tomography angiography for detecting in-stent restenosis. Heart 2008;94:848–854. Migliavacca F, Petrini L, Colombo M, Auricchio F, Pietrabissa R. Mechanical behavior of coronary stents investigated through the finite element method. J Biomech 2002;35:803–811. Colombo A, Stankovic G, Moses JW. Selection of coronary stents. J Am Coll Cardiol 2002;40:1021–1033. Grewe PH, Deneke T, Machraoui A, Barmeyer J, M€ uller K-M. Acute and chronic tissue response to coronary stent implantation: Pathologic findings in human specimen. J Am Coll Cardiol 2000; 35:157–163. Lally C, Dolan F, Prendergast PJ. Cardiovascular stent design and vessel stresses: A finite element analysis. J Biomech 2005;38: 1574–1581.
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27. Liang DK, Yang DZ, Qi M, Wang WQ. Finite element analysis of the implantation of a balloon-expandable stent in a stenosed artery. Int J Cardiol 2005;104:314–318. 28. Rogers C, Tseng DY, Squire JC, Edelman ER. Balloon-artery interactions during stent placement: A finite element analysis approach to pressure, compliance, and stent design as contributors to vascular injury. Circ Res 1999;84:378–383.
29. Wu W, Wang W-Q, Yang D-Z, Qi M. Stent expansion in curved vessel and their interactions: A finite element analysis. J Biomech 2007;40:2580–2585. 30. Tanaka E, Tanne K, Sakuda M. A three-dimensional finite element model of the mandible including the TMJ and its application to stress analysis in the TMJ during clenching. Med Eng Phys 1994; 16:316–322.
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Research Center for Biomedical Implants and Microsurgery Devices, Taipei Medical University, Taipei 110, Taiwan Research Center for Biomedical Devices and Prototyping Production, Taipei Medical University, Taipei 110, Taiwan 3 Department of Diagnostic Radiology, Taipei Medical University Hospital, Taipei 110, Taiwan 4 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan 5 Department of Dentistry, Sijhih Cathay General Hospital, Taipei 221, Taiwan 6 Department of Physiology Faculty of Medicine Hasanuddin University, 90245, Makassar, Indonesia 7 Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan 8 Department of Dentistry, Taipei Medical University-Shuang Ho Hospital, Taipei 235, Taiwan 2
Received 16 September 2013; revised 21 November 2013; accepted 11 March 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35172 Abstract: The purpose of this research was to investigate stresses resulting from different thicknesses and compositions of hydrogenated Cu-incorporated diamond-like carbon (a-C:H/Cu) films at the interface between vascular stent and the artery using three-dimensional reversed finite element models (FEMs). Blood flow velocity variation in vessels with plaques was examined by angiography, and the a-C:H/Cu films were characterized by transmission electron microscopy to analyze surface morphology. FEMs were constructed using a computer-aided reverse design system, and the effects of antibacterial nanostructured composite films in the stress field were investigated. The maximum stress in the vascular stent occurred at the intersections of net-like structures. Data
analysis indicated that the stress decreased by 15% in vascular stents with antibacterial nanostructured composite films compared to the control group, and the stress decreased with increasing film thickness. The present results confirmed that antibacterial nanostructured composite films improve the biomechanical properties of vascular stents and release abnormal stress to prevent restenosis. The results of the present study offer the clinical benefit of inducing superior C 2014 Wiley Periodibiomechanical behavior in vascular stents. V cals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2014.
Key Words: 3D-reversed model, biomechanics, finite element analysis, surface treatment, vascular stent
How to cite this article: Han-Yi Cheng, Wen-Tien Hsiao, Li-Hsiang Lin, Ya-Ju Hsu, Andi Wardihan Sinrang, Keng-Liang Ou. 2014. Effects of antibacterial nanostructured composite films on vascular stents: hemodynamic behaviors, microstructural characteristics, and biomechanical properties. J Biomed Mater Res Part A 2014:00A:000–000.
INTRODUCTION
Angioplasty is accepted as a safe technique for treating myocardial infarction, coronary artery heart disease, and thrombus. Figure 1 shows magnetic resonance images (MRIs) of plaques in the neck artery before and after stenting. The clinical effects of stenting are influenced by various factors such as inadequate balloon expansion, artery injury, stent recoil, and restenosis, which is the most critical problem. In the 1980s, neointimal hyperplasia and elastic recoil were investigated extensively, and many cardiologists researched methods to eliminate these problems.1,2 Previously, neointimal hyperplasia occurred approximately
in 40% of patients within 326 months after stenting. Subsequently, a repeat of the procedure was usually performed for restenosis.3,4 Coated-surface technology is widely used in medical devices because of their outstanding biocompatibility properties. Diamond-like carbon (DLC) has been proposed for use in blood-contacting devices5–7 such as electrosurgical devices, artificial hearts, mechanical heart valves, and artery stents.8,9 Various reports have shown that the anticoagulation property of DLC is related to the bonding structure, hydrophobicity, and smooth surface.10,11 Restenosis is a common problem after stenting because of vessel
*Co-first author Correspondence to: K.-L. Ou; e-mail: [email protected] Contract grant sponsor: Department of Health, Executive Yuan, Taiwan; contract grant number: MOHW103-TDU-N-211-133001 Contract grant sponsor: International Congress of Oral Implantologists; contract grant number: A-101-057
C 2014 WILEY PERIODICALS, INC. V
1
FIGURE 1. MRIs of blood flow (arrow) in the artery with plaques (a) before and (b) after stenting operation.
overloading, and platelet adhesion and activation. However, a DLC film is suitable to prevent blood clotting.12,13 Finite element analysis (FEA) is a useful tool that could be applied to quantify the biomechanical behavior in the vascular stent and surrounding arteries. FEA has been used to study the biomechanical behavior of various medical applications, including temporomandibular joint replacement, dental implants, and vascular stents under a number of loading conditions.14,15 Hydrogenated Cu-incorporated a-C:H/Cu films were prepared in the present study using a radiofrequency (RF) plasma magnetron sputtering system at various CH4/Ar gas ratios. The use of a-C:H/Cu films as promising anticoagulation and antibacterial coatings for biomedical applications was examined. The mechanical behavior at the stent–artery interface is an important factor for the clinical success of stenting; however, investigations of this behavior through experimental and theoretical analyses have thus far been scarce. To examine the biomechanical behavior of film-coated stents, the magnitude and location of the maximum stresses must be determined. Therefore, the aim of the present study was to examine the use of three-dimensional (3D) finite element models (FEMs) to quantify the maximum stresses in vascular stents with nanostructured composite films. MATERIALS AND METHODS
Angiography test Angiography is a biomedical imaging technique that is used to visualize blood vessels in the human body, such as arteries, veins, and heart chambers can be observed using contrast media. The arm vessels of six patients were selected because the vascular image of the arm is more stable than that of other parts. A special gray scale range for blood was adopted to show the regions of blood flow, and noise points could be erased. Variation in the gray scale at each moment could be used to determine the changes in blood flow. Preparation and evaluation of the a-C:H/Cu film A deposition process that combined RF plasma and a magnetron sputtering system was used to deposit the a-C:H/Cu film on a glass substratum (diameter, 1 cm; thickness, 2
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FIGURE 2. 3D FEM of the vascular stent and artery with plaques. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
mm). Various gas mixture ratios of CH4/Ar were fed into the chamber to deposit onto the films after the cleaning process.16 For deposition of the a-C:H/Cu films, nano-Cu particles were generated by sputtering a copper target (99.99% purity), which was fixed at 60 mm directly above the substratum. The microstructures of the deposited films were examined with a high-resolution transmission electron microscope (TEM, PHILIPS F-20) operated at 250 kV. 3D-reversed model analysis The 3D image models were built using the ANSYS Workbench 12.1 (ANSYS) finite element program. The vascular stents and arteries were regarded as continuous integers. Figure 2 shows a vascular stent of the standard type (Biosensors International Group; outer diameter: 3.0 mm, thickness: 0.1 mm). Clinical MRI showed that the artery had an outer diameter of 4.5 mm and a thickness of 0.5 mm, with plaques extending 5 mm and showing a central thickness of 0.5 mm. According to hyperelastic material laws, unloading follows the initial response of the stress-strain relationship, which is the rule for soft tissues in biomechanics. The balloon (diameter: 2.8 mm) was modeled in a cylindrical shape. The balloon simulated procedure was divided into two phases. The two important processes involved were converging and reinforcing of the mesh, which allow the model to approximate the actual object more accurately. Because of the deformation requirement, three types of elements were used in the present models: a 20-node solid element (Solid186) was used for the vascular stent. A fournode shell element (Shell181) was used for the balloon, and an eight-node hyperelastic element (Hyper58) was adopted in the artery. The numbers of nodes and elements were 19,852–20,412 and 12,699–13,462, respectively. The vascular stent is characterized by the properties of the 316L
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FIGURE 3. Angiography test of artery with plaques (arrow). (a) t 5 0.015 s, (b) t 5 0.020 s, (c) t 5 0.025 s, and (d) t 5 0.030 s (lift: clinical image and right: pixel image).
stainless steel. The biomechanical properties of the a-C:H/ Cu film, and tissue have been described in previous studies.17,18
In the present study, the parameters were categorized into two groups on the basis of the thickness of the coated film and the percentage of the metallic Cu element. The thicknesses of these coated films varied from 0 (control group) to 500 lm, and all models simulated with different percentages of metallic Cu element varied from 0% to 80%, for comparison. The von Mises stresses of the vascular stent and the artery were investigated in this study.
RESULTS
FIGURE 4. TEM (a) top view and (b) cross-section image of the a-C:H/ Cu film.
Figure 3 shows the blood flow velocity variation in vessels with plaques. The blood flow decreased through the narrow parts of vessels. The pixel of blood suddenly stopped increasing, and it indicated the blood was jammed because of plaques. Blood velocity decreased by >20% of the initial value. The present of plaques blocked blood flow and decreased the blood velocity, resulting in an increase in stress. To better understand the effect of Cu doping on the microstructural variation in the a-C:H film, the samples were subjected to TEM. Figure 4(a) shows the top-view image of the TEM and the corresponding selected area electron diffraction pattern (SAEDP) of the a-C:H/Cu film. Cu doping resulted in the embedding of sphere-like nanoparticles became embedded in the film. Moreover, the SAEDP consisting of ring spots revealed the presence of nanopolycrystalline structures in the film. The size and number of nano-Cu particles were proportional to the Cu content. Therefore, the production of a-C:H/ Cu films varied with the CH4/Ar ratio, and transformation of the amorphous-like phase into a nanopolycrystalline phase was induced by Cu doping/ion bombardment and radical reactions. Figure 4(b) shows a TEM cross-section image showing Cu particles embedded in the DLC film, and crystallized within molecular system. The highest stresses occurred at the intersections of the net-like structure in the vascular stent models. Figure 5
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FIGURE 5. Von Mises stress distributions of vascular stent in the (a) control group and (b) a-C:H/Cu—500:80 group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
shows the von Mises stress distribution in the vascular stent with a 500 nm a-C:H/Cu film with 80% metallic Cu element (a-C:H/Cu—500:80) and without a-C:H/Cu film (control group). The highest stress in the vascular stent of the control group was 719.22 MPa, and that in the nanostructured film group varied between 597.62 and 715.40 MPa (Fig. 6). On the other hand, the stress distribution was more uniform among the group of thicker coated films. Remarkably, the maximum von Mises stress was reduced by 16.91% in the a-C:H/Cu— 500:80 group, relative to the control group. The stress distribution showed significant stress in the untreated group. Surface treatments were shown to have the potential to decrease the abnormal stress concentration in the vascular stent. In the artery, the maximum stresses were observed at the intersections of the net-like structure of stents as shown in Figure 7. The highest stress for the artery was >10% lower in the aC:H/Cu—500:80 group than in the control group. Coated layers decreased the stresses at the interface between the vascular stent and the artery. Although no significant differences in the maximum stresses were detected between the groups with different percentages of the metallic Cu element, the maximum von Mises stress in the vascular stent and
FIGURE 6. Highest stresses of vascular stent in different thickness of a-C:H/Cu film and different percentage of metallic Cu element. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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artery was slightly smaller in the groups with a metallic Cu element than in those without. As described previously, data analysis indicated deduced stresses in vascular stents and arteries resulting from the a-C:H/Cu film, although the maximum stresses did not differ significantly between the films with and without a metallic Cu element. In our study, the maximum stress was observed at intersections of the net-like structure. Applied stress is considered one of the most important factors determining the effectiveness of vascular stents. DISCUSSION
DLC has excellent mechanical, tribological, and biological properties. The properties of DLC film can be changed within a certain range by adding other elements. We found that nano-Cu particles were embedded into the film of the samples when the a-C:H film was deposited with a Cu target under various CH4/Ar ratios. Moreover, a-C:H/Cu films were nontoxic to MG-63 and NIH-3T3 cells. Nano-Cu particles have an important role in the antibacterial mechanisms of a-C:H/Cu films. Metallic Cu elements (probably Cu1 ions or nano-Cu particles) can diffuse from the film and efficiently kill bacteria by destroying their cell walls and membranes, thereby causing their cytoplasm to leak. The a-C:H films with a Cu content have antibacterial properties against both Escherichia coli and Staphylococcus aureus. Thus, the a-C:H/ Cu film can be considered a promising antibacterial coating for applications in biomedical science and for minimally invasive surgery devices.19 Many types of image processing methods, such as grayscale discrimination, sobel filter, background subtraction, and time difference between frames are used to track and detect the contours of objectives.20–22 In the present study, the vascular structure was rebuilt by using a similar method. All the gray-scale images were executed to detect contour and noise points were eliminated by combining background subtraction method and the time difference between frames method. Vascular stents are small tube-like structures used to expand the vessel wall and restore blood flow perfusion in stenotic arteries. The stent is equipped with a balloon catheter that is delivered to the site of the plaque. As the balloon is inflated, the stent expands and is pressed against the inner vessel wall. Then, the balloon is
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FIGURE 7. Von Mises stress distributions of artery in the (a) control group and (b) a-C:H/Cu—500:80 group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
deflated and removed, and the stent remains in place to keep the vessel open. Stenting is a simpler method of solving plaque problems than traditional operations. Migliavacca et al.23 reported that stents with a lower metal-to-artery surface ratio result in a higher radial and longitudinal recoil, but a lower dogboning; the thickness also influences the stent performance in terms of recoil and dogboning. Thinner stents are associated with reduced dogboning, foreshortening, and longitudinal recoil, whereas the radial recoil is not significantly affected by the thickness. Moreover, as the slot length of the stent increases, the radial recoil increases as well. Many clinical studies have shown that the performance of vascular stents and differs stents cause different restenosis rates, which are reported to be approximately 20– 50%.24,25 Overloading may induce a greater response to injury on the vessel wall, ultimately resulting in restenosis; therefore, decreasing stress in the artery could prevent restenosis. Prendergast compared two different designs of vascular stents, the S7 (Medtronic AVE) and the NIR (Boston Scientific).26 The results of the assessment of vessel wall stresses in the stented arteries indicated that the stress to stenosis vessel was lower with the S7 stent design than with the NIR stent. These results correlated with clinical
FIGURE 8. Highest stresses of artery in different thickness of a-C:H/Cu film and different percentage of metallic Cu element. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
restenosis rates, as higher restenosis rates have been associated with the NIR design than with the S7 design. The influence of the angioplasty balloon configuration has been examined in several studies.27,28 Different typical angioplasty balloons affect the deployment of a stent to different degrees. The results of the present study indicated that balloon configuration affects the transient behavior of the vascular stent as well as the mechanical environment of the artery. The functions of vascular stents in a curved and straight vessel were compared in 2006.29 The results showed that the curved vessel model was straightened by stenting, and a hinge effect was observed at the stent. The maximum tissue prolapse of the curved vessel model was more severe than that of the straight one. The minimum lumen area of the curved vessel was decreased, compared to that of the straight vessel model. The highest stresses in the vessel were concentrated in the inner curvature of the curved vessel model, and the stress distribution of the straight vessel was similar to that of our results. FEMs are used in mechanical engineering analysis and design to evaluate potential decay. They have been successfully used in biological applications in various medical devices. In the biomedical field, models have been used to determine stresses in different biological structures, such as the facial skeleton, dental implants, and for vascular stents. Most of these FEA studies have analyzed the biomechanical behavior of individual structures or materials. However, biomechanical models of the vascular stent’s FEM are not perfect; overall, they are based on a number of assumptions and simplifications.30 An accurate comparison of our results with those obtained using FEM in previous studies is difficult because of various differences in the properties of the material, balloon expansion forces, the mesh structures, and the constrained conditions used in these models. In the present study, we considered three main materials: 316L stainless steel, a-C:H/Cu, and vessel tissue. The Young’s modulus of Cu is lower than that of DLC. Therefore, increasing the percentage of Cu will result in a softening effect on the a-C:H/Cu film to decrease stress. Moreover, the Cu element is characterized by face-centered cubic structure with many slipping planes. An increased number of Cu particles increase the slipping planes in the film. The slipping plane can be used as buffer layer to absorb stress. Therefore, the stress is decreased as the Cu particles in the film increase.
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Although the maximum stress of the stent was below the reasonable range of the 316L stainless steel material, consideration of fatigue damage was necessary because many vascular stents fail because of fatigue destruction induced by blood flow. The stresses caused by all the elements were released by the coated effect. The coated film not only contributed toward an improved biomechanical behavior, but also resulted in outstanding biocompatibility, as described in a previous study.16 Our study provided useful information on stress distribution and the most probable maximum stress locations for vascular stents. The limitations of our study are as follows: (1) we used a uniform type of vascular stent; (2) the viscoelasticity of the artery was considered; (3) the model did not include the influence of blood flow; and (4) this study was based on a theoretical analysis.
8.
9.
10.
11.
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CONCLUSION
Although previous studies have used FEA to examine vascular stents, few models have built stents with antibacterial nanostructured composite film. In the present study, this factor was considered important because evidence had indicated that the coated film is a critical factor for stress, and that overloading may induce a greater response to injury on the vessel wall, ultimately resulting in restenosis. Therefore, the interaction stress between the vascular stent and the artery is considered as an important factor. The aim of the present study was to understand the interface stress distribution in stenting operations. Our results indicate that vascular stents with a-C:H/Cu films may decrease overloading stress and release abnormal stress concentration to prevent restenosis. The present data suggest the clinical benefit of inducing a superior biomechanical behavior of the vascular stent.
13.
REFERENCES
18.
1. Jia H, Liu H, Kong J, Hou J, Wu J, Zhang M, Tian J, Liu H, Ma L, Hu S, Huang X, Zhang S, Zhang S, Yu B, Jang IK. A novel polymer-free paclitaxel-eluting stent with a nanoporous surface for rapid endothelialization and inhibition of intimal hyperplasia: Comparison with a polymer-based sirolimus-eluting stent and bare metal stent in a porcine model. J Biomed Mater Res Part A 2011;98A:629–637. 2. Yin T-Y, Wang G-X, Zhang D-C, Du D-Y, Li Z-G, Luo L-L, Hou Y-B, Wang Y-Z, Zhao J-B. Endothelialization and in-stent restenosis on the surface of glycoprotein IIIa monoclonal antibody eluting stent. J Biomed Mater Res Part A 2012;100A:1398–1406. 3. Stewart HJS, Guildford AL, Lawrence-Watt DJ, Santin M. Substrate-induced phenotypical change of monocytes/macrophages into myofibroblast-like cells: A new insight into the mechanism of in-stent restenosis. J Biomed Mater Res Part A 2009;90A: 465–471. 4. Indolfi L, Causa F, Giovino C, Ungaro F, Quaglia F, Netti PA. Microsphere-integrated drug-eluting stents: PLGA microsphere integration in hydrogel coating for local and prolonged delivery of hydrophilic antirestenosis agents. J Biomed Mater Res Part A 2011;97A:201–211.
15.
16.
17.
19.
20.
21.
22.
23.
24.
5. Hauert R. A review of modified DLC coatings for biological applications. Diamond Relat Mater 2003;12:583–589.
25.
6. Fedel M, Motta A, Maniglio D, Migliaresi C. Surface properties and blood compatibility of commercially available diamond-like carbon coatings for cardiovascular devices. J Biomed Mater Res Part B: Appl Biomater 2009;90B:338–349.
26.
7. Krishnan LK, Varghese N, Muraleedharan CV, Bhuvaneshwar GS, Derange`re F, Sampeur Y, Suryanarayanan R. Quantitation of pla-
6
14.
CHENG ET AL.
telet adhesion to Ti and DLC-coated Ti in vitro using 125I-labeled platelets. Biomol Eng 2002;19:251–253. Lee B, Shin H-S, Park K, Han D. Surface grafting of blood compatible zwitterionic poly(ethylene glycol) on diamond-like carboncoated stent. J Mater Sci: Mater Med 2011;22:507–514. Kim JH, Shin JH, Shin DH, Moon M-W, Park K, Kim T-H, Shin KM, Won YH, Han DK, Lee K-R. Comparison of diamond-like carboncoated nitinol stents with or without polyethylene glycol grafting and uncoated nitinol stents in a canine iliac artery model. Br J Radiol 2011;84:210–215. McLaughlin JA, Meenan B, Maguire P, Jamieson N. Properties of diamond like carbon thin film coatings on stainless steel medical guidewires. Diamond Relat Mater 1996;5:486–491. Roy RK, Lee KR. Biomedical applications of diamond-like carbon coatings: A review. J Biomed Mater Res Part B: Appl Biomater 2007;83:72–84. Yang P, Huang N, Leng YX, Chen JY, Fu RKY, Kwok SCH, Leng Y, Chu PK. Activation of platelets adhered on amorphous hydrogenated carbon (a-C:H) films synthesized by plasma immersion ion implantation-deposition (PIII-D). Biomaterials 2003;24:2821–2829. Snyder TA, Tsukui H, Kihara SI, Akimoto T, Litwak KN, Kameneva MV, Yamazaki K, Wagner WR. Preclinical biocompatibility assessment of the EVAHEART ventricular assist device: Coating comparison and platelet activation. J Biomed Mater Res Part A 2007;81A: 85–92. Cheng H-Y, Chu K-T, Shen F-C, Pan Y-N, Chou H-H, Ou K-L. Stress effect on bone remodeling and osseointegration on dental implant with novel nano/microporous surface functionalization. J Biomed Mater Res Part A 2013;101A:1158–1164. Chu K-T, Cheng H-Y, Pan Y-N, Chen S-Y, Ou K-L. Enhancement of biomechanical behavior on osseointegration of implant with SLAffinity. J Biomed Mater Res Part A 2013; 101A:1195–1200. Lee F-P, Wang D-J, Chen L-K, Kung C-M, Wu Y-C, Ou K-L, Yu C-H. Antibacterial nanostructured composite films for biomedical applications: Microstructural characteristics, biocompatibility, and antibacterial mechanisms. Biofouling 2013;29:295–305. Chung J-W, Lee C-S, Ko D-H, Han JH, Eun KY, Lee K-R. Biaxial elastic modulus of very thin diamond-like carbon (DLC) films. Diamond Relat Mater 2001;10:2069–2074. Heckmann O, Magnan H, le Fevre P, Chandesris D, Rehr JJ. Crystallographic structure of cobalt films on Cu(001): Elastic deformation to a tetragonal structure. Surf Sci 1994;312:62–72. Zhang K, Liu T, Li J-a, Chen J-y, Wang J, Huang N. Surface modification of implanted cardiovascular metal stents: From antithrombosis and antirestenosis to endothelialization. J Biomed Mater Res Part A 2013:n/a-n/a. n C, Miller M, Blomgren P. Structure enhancement diffusion Baza and contour extraction for electron tomography of mitochondria. J Struct Biol 2009;166:144–155. Bouma CJ, Niessen WJ, Zuiderveld KJ, Gussenhoven EJ, Viergever MA. Automated lumen definition from 30 MHz intravascular ultrasound images. Med Image Anal 1997;1:363–377. Pugliese F, Weustink AC, Van Mieghem C, Alberghina F, Otsuka M, Meijboom WB, van Pelt N, Mollet NR, Cademartiri F, Krestin GP, Hunink MG, de Feyter PJ. Dual source coronary computed tomography angiography for detecting in-stent restenosis. Heart 2008;94:848–854. Migliavacca F, Petrini L, Colombo M, Auricchio F, Pietrabissa R. Mechanical behavior of coronary stents investigated through the finite element method. J Biomech 2002;35:803–811. Colombo A, Stankovic G, Moses JW. Selection of coronary stents. J Am Coll Cardiol 2002;40:1021–1033. Grewe PH, Deneke T, Machraoui A, Barmeyer J, M€ uller K-M. Acute and chronic tissue response to coronary stent implantation: Pathologic findings in human specimen. J Am Coll Cardiol 2000; 35:157–163. Lally C, Dolan F, Prendergast PJ. Cardiovascular stent design and vessel stresses: A finite element analysis. J Biomech 2005;38: 1574–1581.
EFFECTS OF ANTIBACTERIAL NANOSTRUCTURED COMPOSITE FILMS
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27. Liang DK, Yang DZ, Qi M, Wang WQ. Finite element analysis of the implantation of a balloon-expandable stent in a stenosed artery. Int J Cardiol 2005;104:314–318. 28. Rogers C, Tseng DY, Squire JC, Edelman ER. Balloon-artery interactions during stent placement: A finite element analysis approach to pressure, compliance, and stent design as contributors to vascular injury. Circ Res 1999;84:378–383.
29. Wu W, Wang W-Q, Yang D-Z, Qi M. Stent expansion in curved vessel and their interactions: A finite element analysis. J Biomech 2007;40:2580–2585. 30. Tanaka E, Tanne K, Sakuda M. A three-dimensional finite element model of the mandible including the TMJ and its application to stress analysis in the TMJ during clenching. Med Eng Phys 1994; 16:316–322.
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