不鏽鋼表面固定生物高分子應用於釋藥型心血管支架之製備與探討

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研究生：	黃皪瑩 Li-Ying Huang
論文名稱：	不鏽鋼表面固定生物高分子應用於釋藥型心血管支架之製備與探討 Study of Biopolymer Immobilization on Stainless steel for Durg-Eluting Stent
指導教授：	楊銘乾 Ming-Chien Yang
口試委員:	張豐志 none 楊台鴻 none 王大銘 none 李振綱 Cheng-Kang Lee
學位類別：	博士 Doctor
系所名稱：	工程學院 - 材料科學與工程系 Department of Materials Science and Engineering
論文出版年：	2008
畢業學年度：	96
語文別：	英文
論文頁數：	99
中文關鍵詞：	藥物釋放型支架、藥物釋放、血液相容性、內皮細胞、平滑肌細胞、生物高分子、SUS316L不鏽鋼
外文關鍵詞：	SUS316L stainless steel, biopolymer, drug-eluting stent, drug controlled release, hemocompatibility, smooth-muscle cells, endothelial cells
相關次數：	點閱：386 下載：1
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新一代包覆藥物型心導管支架(stent)，目前已經慢慢取代傳統不鏽鋼的stent，主要的概念在於包覆一層高分子材料，以降低不鏽鋼直接摩擦血管及提升生物相容性，並且可在高分子裡面包覆藥物，降低血栓形成、抗發炎反應及抑制平滑肌細胞(smooth muscle cells)成長於stent上去形成再狹窄(restenosis)的情況發生，雖然目前大都未通過FDA的認證，但是還有很大的空間等待我們去發掘研究，是目前生醫界最熱門的研究題目之一。
此論文的第一部份主要著重在於透明質酸(HA)/肝素(HEP)的表面接枝於SSU316L 不鏽鋼表面之血液相容性及包覆藥物其藥物釋放之情形。我們使用ATMS為不鏽鋼-高分子的表面接著劑，接著HA及HEP被共價鍵結於不鏽鋼板上（1-5層）。AFM、ESCA、接觸角及橢圓儀將被使用來評估接枝層的表面特性。結果顯示藉由橢圓儀的量測，HA/HEP接枝厚度約為280-630 nm，而在ESCA上也可以證實HA與HEP的確能共價鍵
結於基版上。在血液相容性測試上，結果發現HA/HEP接枝層可以明顯延長凝血時間(APTT)，及減少血小板的吸附，證明血液相容性已經被改善。另外，在藥物釋放方面，sirolimus藥物包覆量約為1.02~3.12 g/cm2，且在5層的接枝層上其釋放天數可以超過30天，達到延長釋放的效果。
此論文的第二部份主要著重在於硫酸軟骨素(Chs)/肝素(HEP)的表面接枝於Au塗佈之SSU316L不鏽鋼表面，並探討改質後的表面之血液相容性及藥物對於平滑肌及內皮細胞的影響。我們使用DMSA（硫醇類）作為不鏽鋼及高分子的連結劑，藉由硫醇化(thiolizing)與Au之反應來作共價鍵結。結果顯示sirolimus藥物能有效抑制平滑肌細胞生長避免再狹窄的機率發生，但並不影響內皮細胞的成長。另一方面，改質的表面一樣也可以改善不鏽鋼板的血液相容性。
第三部分，將之前接枝之條件，實際使用接枝在stent上，利用螢光顯微鏡觀察可以發現類似之前的情況，sirolimus的包覆可以抑制平滑肌細胞的成長去避免再狹窄的情況發生，但內皮細胞依然可以正常代謝。因此，此生物高分子改質及包覆藥物之心導管支架能被預期去改善血管再狹窄及血栓(thrombus)形成，對於心血管病患將是一大福音。

This thesis is aiming to develop a drug-eluting stainless steel stent to curtail in-stent restenosis induced by conventional stents. The purpose to coat biomolecules is to avoid the friction of blood vessel to improve biocompatibility, to load drug to decrease the formation of thrombus, inflammation, and the growth of smooth muscle cells to prevent the formation of restenosis.
The first part is focused on stainless steel (SUS316L) sheets coated with hyaluronic acid (HA) and heparin (HEP), and their in vitro characteristics and drug release pattern were investigated. The surface of stainless steel (SS) was treated with nitric acid and followed by anchoring aminotrimethoxysilane (ATMS), then a nanolayer of HA was covalently immobilized onto the surface. A model drug (sirolimus) was embedded in assembled HA/HEP layers at a density ranging from 1.02 to 3.12 g/cm2. Heparin was then covalently bonded to the HA-immobilized SS substrate. After repeating 1 to 5 cycles, 1 to 5 layers of polyelectrolyte complex (PEC) nanobrush of HA/HEP were resulted with the thickness ranging from 280 to 630 nm (measured with ellipsometry). The SS-ATMS-HA-HEP substrates were evidenced by X-ray photoelectron spectroscope (XPS), contact angle, and AFM measurement. The effect of this surface modification on the coagulation time of the resulting SS substrates was investigated. The results show that the multi-layer HA/HEP stainless steel would exhibit longer coagulation time than pure SS substrates. In addition, the results of the in vitro drug delivery study showed that release of sirolimus from the 5-layer-HA-HEP stainless steel was able to maintain more than 30 days. Thus layer-by-layer HA/HEP PEC can improve the hemocompatibility of SS surface and control the drug released rate by multiple layers of HA/HEP PEC.
The second part is focused on a thin layer of gold sputtered onto SUS316L stainless steel (SS) sheet. After thiolizing the Au layer with dimercaptosuccinic acid (DMSA), layers of chondroitin 6-sulfate (ChS) and heparin (HEP) were alternatively immobilized on the Au-treated SS. The resulting stent would be both anti-atherogenic and anti-thrombogenic. After repeating 1 to 5 cycles, 1 to 5 layers of polyelectrolyte complex (PEC) of ChS/HEP were successfully fabricated. Sirolimus was loaded in the ChS/HEP layers. The SS-ChS-HEP surface was examined by X-ray photoelectron spectroscopy (XPS), contact angle, and atomic force microscopy (AFM) measurement. Biological tests including hemocompatibility, drug release pattern, and the inhibition of smooth muscle cell proliferation were also performed. The results show that the multilayer of ChS/HEP exhibits longer blood clotting time than pure SS substrates. Therefore this biopolymer multilayer can avoid thrombosis on the stainless. The releasing rate of sirolimus can be controlled through the number of ChS/HEP PEC layers. With a five-layer coating, sirolimus can be released continuously for more than 20 days. Furthermore, the multi-layer ChS/HEP loaded with sirolimus can suppress specifically to the growth of smooth-muscle cells to avoid restenosis.
The third part is focused on the metallic stent coating according to previous optimum procedure. Similar to past investigation, the resulting samples of loading sirolimus stents could prevent the proliferation of smooth muscle cells, but did not affect the growth of endothelia cells examined by fluorescence microscopy.
It can be anticipated that these multi-layer biomolecules coated on the stainless steel stent might be applied in biomedical devices, such as drug eluting stents.

Contents

致謝		I
摘要		II
Abstract		IV
Contents		VI
Figures		VIII
Tables		XII
Chapter 1: Introduction	1
1.1. Hyaluronic Acid/Heparin Nanostructure Coating	1
1.2. Au and Chondroitin 6-sulfate/ Heparin Nanostructure Coating	3
Chapter 2: Literature Review and Theory	7
2.1. Introduction of Drug-Eluting Stent	7
2.2. Polymer Technique to Encapsulate Drug	10
2.3. Endothelia Cells	13
2.4. Smooth Muscle Cells	15
2.5. Blood coagulation and blood-materials interactions	16
2.6. Platelets formation	16
2.7. Analysis of platelet responses	19
2.8. Coagulation	20
2.9. The membranes Graft	24
2.10. Immobilization methods	27
2.11. Evaluation methods of blood compatibility for polymer surfaces 	30
2.12. Heparin-containing bioactive surfaces	31
2.13. Bioactive surfaces of cardiovascular stent	32
2.14. Contact Angle Methods	33
2.15. Electron Spectroscopy for Chemical Analysis	34
Chapter 3: Experiment Methods	38
3.1. A flow sheet of our works	38
3.2. Materials	39
3.2.1 Hyaluronic Acid	39
3.2.2 Heparin	39
3.2.3 Chondroitin-6-sulfate	40
3.2.4 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)	40
3.2.5 Aminotrimethoxysilane (ATMS)	41
3.2.6 Dimercaptosuccinic acid	42
3.2.7 Sirolimus	42
3.3. Experiment materials	43
3.3.1 Hyaluronic acid and heparin immobilization	43
3.3.2 Chondroitin 6-sulfate and heparin immobilization	45
3.3.3 Surface characterization	47
3.3.4 Blood coagulation time	48
3.3.5 Drug release test	48
3.3.6 Evaluation of platelet adhesion	49
3.3.7 Cell culture	50
3.3.8 Methylthiazol tetrazolium (MTT) assay	51
3.3.9 Immuno-fluorescence staining	51
Chapter 4: Results and Discussion	53
4.1.  Hyaluronic Acid/Heparin Nanostructure Coating	53
4.1.1. Surface characterization analysis	53
4.1.2. Blood coagulation	61
4.1.3. Platelet Adhesion	63
4.1.4. Drug release test	66
4.2.  Au and Chondroitin 6-sulfate/ Heparin Nanostructure Coating	69
4.2.1. Multilayer characterization and Contact angle	69
4.2.2. XPS assay	70
4.2.3. AFM and spectroscopic ellipsometer assay	73
4.2.4. Anti-thrombus properties	76
4.2.5. Drug release test	78
4.2.6. Cell proliferation assay	80
4.3.  Metical stent Coating	84
Chapter 5 : Conclusions	88
References		90





Figures

Figure 1. 1.  Scheme of percutaneous transluminal coronary angioplasty (PTCA) by     cardiovascular stent	1
Figure 1. 2.  Illustration of alginic acid-immobilization scheme	2
Figure 2. 1.  (a) Stent is mounted on a balloon catheter and advanced to the diseased, narrowed portion of the heart artery; (b) The balloon is inflated  and stent is expanded, which opens the narrowed section of the artery; (c) The balloon is deflated and removed; the stent is embedded into the wall of the artery and stays in position. Medication coats drug-eluting stents and reduces the chance of renarrowing, or restenosis, of the blood vessel	8
Figure 2. 2. Product of Drug-eluting stent..................................................................10
Figure 2. 3. Diagram of location of endothelia and smooth muscle cells in the human skin	13
Figure 2. 4. Known secretory/ ecpression products of endothelia cells relating to vessel physiology [B.E. Sumpio, J.T. Riley, A. Dardik, Int J Biochem Cell B 34 (2002) 1508-1512	14
Figure 2. 5. Image of human smooth muscle cells.....................................................15
Figure 2. 6. Platelet structures	17
Figure 2. 7. Platelet reactions to artificial surfaces.  Following protein adsorption factor 4(PF4) and -thromboglobulin (TG), and dense granule contents, including ADP.  Thrombin is generated locally through factor XIIa and platelet pro-coagulant activity. Thromboxane A2 (TxA2) is synthesized. ADP, TxA2, and thrombin recruit additional circulating platelets into an enlarging platelet aggregate.  Thrombin-generated fibrin stabilizes the platelet mass	18
Figure 2. 8. Diagrammatic depiction of platelet spreading divided into five shape categories for analysis. From left to right,these stages of spreading are defined as follows: round (R) or discoid: no pseudopodia present; dendritic (D) or early pseudopodial: one or more pseudopodia with no evident flattening; spread dendritic (SD) or intermediate pseudopodial: one or more pseudopodia flattened, hyaloplasm not spread between pseudopodia; spreading (S): hyaloplasm spread between pseudopodia; and fully spread (FS): hyaloplasm extensively spread, no distinct pseudopodia……......................................................................................19
Figure 2. 9. Schematic representations of platelet adhesion to and spreading behavior and thrombus formation. PMEA(a) and PHEMA (b)	20
Figure 2.10. Mechanisms of clotting factor interactions.  Clotting is initiated by either an intrinsic or extrinsic pathway with subsequent factor interactions which converge upon a final, common path….........................................23
Figure 2.11. Interpretation of common screening tests of blood coagulation	24
Figure 2.12. Various methods for heparinization of surfaces: (A) heparin bound  ionically on a positively charged surface; (B) heparin ionically complexed to a cationic polymer, physically coated on a surface; (C) heparin self-cross-linked physically coated on a surface; (D) heparin, albumin, collagen, and chitosan covalently linked to a surface; (E) heparin covalent immobilized via spacer arms (chitoson); (F) heparin dispersed into a hydrophobic polymer; (G) heparin-chitosan (albumin) conjugate immobilized on a surface	29
Figure 2.13. Various methods for immobilization of albumin on surfaces..................30
Figure 2.14. Heparin-releasing polymers. (A) Heparin (negatively charged) ionically bound onto a positively charged surfaces. (B) Heparin ionically bound to positively charged gel and coated onto a polymer substrate. (C) Heparin-dispersed polymers (diffusion release mechanism). (D) Thermosensitive hydrogel-grafted surface loading heparin in low temperature. (E) Heparin (negatively charged)- positive charged polymer complex (heparin released under electric current	32
Figure 2.15. (A) Cross section diagram of stent which expanded the blood vessel; (B) Thrombus formation with and without MMA/HEMA coating	33
Figure 2.16. Sessile drop method for measuring the contact angle	34
Figure 2.17. Schematic diagram of a monochromatized ESCA instrument	36
Figure 2.18. ESCA is a surface-sensitive method.  Although the X-ray beam can penetrate deeply into a specimen, electrons emitted deep in the specimen (D, E, F, G) will lose their energy in inelastic collisions and never emerge from the surface.  Only those electrons emitted near the surface that lose no energy (A, B) will contribute to the ESCA signal used analytically.  Electrons that lose some energy, but still have sufficient energy to emerge from the surface (C) contribute to the background signal	36
Figure 3. 1.  Chemical structure of Hyaluronic acid	39
Figure 3. 2.  Chemical structure of heparin	40
Figure 3. 3.  Chemical structure of chondroitin 6-sulfate	40
Figure 3. 4.  Chemical structure of EDC	41
Figure 3. 5.  Chemical structure of (3-Aminopropyl)triethoxysilan…………………...41
Figure 3. 6.  Chemical structure of Dimercaptosuccinic acid	42
Figure 3. 7.  Chemical structure of sirolimus	43
Figure 3. 8.  Illustration of ATMS, HA and heparin immobilization	44
Figure 3. 9.  Illustration and chemical reaction of DMSA, ChS and HEP                immobilization	47
Figure 4.1.  Values of contact angles toward distilled water for the surface-modified SUS316L samples (n=5)	54
Figure 4.2.  XPS survey scan spectra of (a) arrayed modified-SUS316L Si2p scan spectra; (b) N1s scan spectra; (c) S2p scan spectra	56
Figure 4.3.  Morphology and roughness of the surface-modified SUS316L samples by AFM: (a) Pure SS; (b) SS-ATMS; (c) 1-layer-HA-HEP; (d) 3-layer-HA-HEP; (e) 5-layer-HA-HEP	60
Figure 4.4.  Anticoagulation times of surface-modified SUS316L, including APTT, PT, FT, and TT (n = 3).The star means the clotting time was (no longer than 500 sec coagulation)	62
Figure 4.5.  (a) Comparison of platelet adhesion of membranes after 30 min, 1 h and 2h incubation (n=3); Image of platelet adhesion (b) without (c) with 5-layer HA/HEP modification observed by metallurgical microscopy	64
Figure 4.6.  Mechanism of heparin activated antithrombin III (ATIII) to inhibit the fibrin formation	65
Figure 4.7. The drug (sirolimus) releasing patterns of surface-modified SUS316L: (a) Cumulative drug released (%) calculated; (b) A plot of ln(Mt/M) versus ln t showed a linear relationship for calculating the values of k and n according to Eq.(3)	68
Figure 4.8.  Contact angles toward distilled water for the surface-modified SS samples (n=5)	70
Figure 4.9.  XPS survey scan spectra of (a) modified-SS Au4f scan spectra; (b) O1s scan spectra; (c) S2p scan spectra	72
Figure 4.10. Morphology of the surface-modified SS samples by AFM: (a) Pure SS; (b) SS-Au; (c) SS-DMSA; (d) SS-(ChS-HEP)1; (e) SS-(ChS-HEP)3; (f) SS-(ChS-HEP)5	75
Figure 4.11. Blood clotting times of surface-modified SS include APTT, PT, FT and TT. (n=5) The star means the clotting time was longer than 500 sec (No coagulation)	78
Figure 4.12. The drug (sirolimus) releasing patterns of surface-modified SS showed a linear relationship for calculating the values of k and n according to Eq. (2) for Mt/M∞ < 0.6 (n=5)	80
Figure 4.13. The morphology of (a-b) ECs and (c-d) SMCs proliferation (15th day) on the SS-(ChS-HEP)5 with and without sirolimus examined by metallurgical microscopy. (50X and inserted images: 200X)	81
Figure 4.14. The comparison of (a) ECs and (b) SMCs proliferation on the SS-(ChS-HEP)5 with and without sirolimus by MTT assay. The star in the (a) means they display insignificant difference, while the double star in the (b) means that they display significant difference. (n=5)	83
Figure 4.15. Metallurgical microscopy image of metallic stents (a) without (b) with Au nanolayer coating by a sputter	84
Figure 4.16. Metallurgical microscopy image of metallic stents (a) without (b) with Chs/HEP polymer brush immobilized and stained by TB dye	85
Figure 4.17. Morphology of (a-b) SMCs and (c-d) ECs proliferation (15th day) on the modified stents with and without sirolimus examined by fluorescence microscopy. (50X and inserted images: 200X)	86
Figure 4.18. Comparison of ECs and SMCs proliferation (15 days) on the 5-layer ChS-HEP coating in the stent with and without sirolimus by MTT assay. The single star means they display insignificant difference, while the double starmeans that they display significant difference. (n=5)	87
Tables

Table 2.1.  The drug-eluting stents which was evaluated to use in the patient in the present	10
Table 2.2.  polymer for cardiovascular devicest	11
Table 2.3.  Potential drug in the drug-eluting stent	12
Table 2.4.  Properties of Human Clotting Factors	21
Table 2.5.  Example of surface-modified biomaterials	26
Table 2.6.  Physical and chemical surface modification methods	27
Table 2.7.  Biio-molecule immobilization methods	28
Table 4.1.  Roughness and drug release parameters (k and n) of the modified stainless steel	59
Table 4.2.  Anticoagulation times of surface-modified SUS316L, including APTT, PT, FT and TT	62
Table 4.3.  Surface characterization and drug release parameters (k and n) of the modified stainless steel	74
Table 4.4.  Blood clotting times of surface-modified SS, including APTT, PT, FT and TT	77
                                

References
Ahn J.S., Choi H.K., Chun M.K., Ryu J.M., Jung J.H., Kim Y.U., Cho C.S., Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro, Biomaterials, 23 (2002) 1411
Amiji MM, Surface modification of chitosan membranes by complexation- interpenetration of anionic polysaccharides for improved blood compatibility in hemodialysis, J Biomed Sci Polym Ed; 8 (1997) 281-298
Andrade JD, Surface and Interfacial Aspects of Biomedical Polymers, Vol. 1: Surface Chemistry and Physics, Plenum Publ., New York.(1985)
Bär F.W., van der Veen F.H., Benzina A., Habets J., Koole L.H., New biocompatible polymer surface coating for stents results in a low neointimal response, J. Biomed. Mater. Res., 52 (2000) 193-198
Baumann H. and Kokott A., Surface modification of the polymers present in a polysulfone hollow fiber hemodialyser by covalent binding of heparin or endothelial cell surface heparin sulfate: Flow characteristics and platelet adhesion, J. Biomed. Sci. Polym. Ed. 11 (2000) 245-272
Bolz A., Amon M., Özbek C., Heublein B., Schaldach M., Coating of cardiovascular stents with a semiconductor to improve their hemocompatibility, Tex. Heart. Inst. J., 23 (1996) 162-166
Bruce I.J., Sen T., surface Modification of Magnetic Nanoparticles with Alkoxysilanes and Their Application in Magnetic Bioseparations, Langmuir 21 (2005) 7029-7035
Brink C., Osterberg E., Holmberg K., Tiberg F., Using poly(ethylene imine) to graft poly(ethylene glycol) or polysaccharide to polystyrene, Colloids Surf. A 66 (1992) 149-156
Brown BA, Coagulation. In Hematology: Principles and Procedures, Lea & Fegiger, Philadelphia. (1984) 179-240
Byun YR, Jacobs H, Kim SW, Heparin surface immobilization through hydrophilic spacers: Thrombin and antithrombin III binding kinetics, J. Biomat. Sci. 6 (1994) 1
Cen L., Neoh K.G., Li Y. and Kang E. T., Assessment of in Vitro Bioactivity of Hyaluronic Acid and Sulfated Hyaluronic Acid Functionalized Electroactive Polymer, Biomacromolecules 5 (2004) 2238-2246
Chan W.C.W., Nie S.,Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection. Science, 281(1998) 2016
Chen K.S., Ku Y.A., Lee C.H., Lin H.R., Lin F.H., Chen T.M., Immobilization of chitosan gel with cross-linking reagent on PNIPAAm gel/PP nonwoven composites surface, Mat Sci Eng C-Bio S, 25 (2005) 472 – 478
Chen M.C., Liang H.F., Chiu Y.L., Chang Y., Wei H.J., Sung H.W., A novel drug-eluting stent spray-coated with multi-layers of collagen and sirolimus, J. Control. Release, 108 (2005) 178-189
Cheng Q., Anna B.T., Permselectivity, Sensitivity, and Amperometric pH Sensing at Thioctic Acid Monolayer Microelectrodes, Anal. Chem., 68 (1996) 4180
Colman RW, Hirsch J, Marder VJ, Salzman EW. Hemostasis and Thrombosis, 3rd ed. Lippincott, New York. (1994) 1-660.
Corrie S.R., Lawrie G.A., Trau M., Quantitative Analysis and Characterization of Biofunctionalized Fluorescent Silica Particles, Langmuir, 22 (2006) 2731-2737
Dion I, Baquey C, Candelon B, Monties JR. Hemocompatibility of titanium nitride, Int J Artif Organs. 15 (1992) 617-621.
Fattori R., Piva T., Drug-eluting stents in vascular intervention, Lancet, 361(2003) 247-249
Fauconnier N., J. Pons N., Roger J., Bee A., Thiolation of Maghemite Nanoparticles by Dimercaptosuccinic Acid, J. Colloid. Interface Sc, 194 (1997) 427-433
Forbes CD and Courtney JM, thrombosis and artificial surfaces. in Haemostasis and thrombosis, Churchill Livingstone, New York. (1987) 902-921.
Frazier R.A., Matthijs G., Davies M.C., Roberts C.J., Schacht E., Tendler S.J.B., Characterization of protein-resistant dextran monolayers, Biomaterials, 21 (2000) 957-966
Frits W.B., Frederik H.V., Abder B., Jo H., Leo H.K, New biocompatible polymer surface coating for stents results in a low neointimal response, J. Biomed. Mater. Res. 52 (2000) 193-198
Goodman S.L., Sheep, pig, and human platelet-material interactions with model cardiovascular biomaterials, J Biomed Mater Res Part A. 45 (1999) 240-250
Groth C.G., Bachman L., Morales J.M., Calne R., Kreis H., Lang P., Touraine J.L., Claesson K., Campistol J.M., Durand D., Wramner L., Brattstrom C., Charpentier B., Sirolimus (rapamycin)-based therapy in human renal transplantation: Similar Efficacy and Different Toxicity Compared with Cyclosporine, Transplantation, 67 (1999) 1036-1042
Guyton AC, Hall JE, Human physiology and Mechanisms of Disease-6th ed. Chapter 26, W. B. Saunders Co., Philadelphia, (1997)
Han D.K., Lee N.Y., Park K.D., Kim Y.H., Cho H.I. and Min B.G., Heparin-like anticoagulant activity of sulphonated poly(ethylene oxide) and sulphonated poly(ethylene oxide)-grafted polyurethane, Biomaterials 16, (1995) 467-471
Hanson SR, Harker LA, Ratner BD, Hoffman AS, In vivo evaluation of artificial surfaces with a nonhuman primate model of arterial thrombosis, J. Lab. Clin. Med. 95 (1980) 289-304
Hoffman AS., Modification of Material Surfaces to Affect How They Interact with Bollda, Ann. N. Y. Acad. Sci. 516 (1987) 96-101
Hong S.Y., Koh Y.S., Chung K.H., Kim D.S., Snake venom disintegrin, saxatilin, inhibits platelet aggregation, human umbilical vein endothelial cell proliferation, and smooth muscle cell migration, Thromb. Re, 105 (2002) 79-86
Huang L.Y., Yang M.C., Hemocompatibility of layer-by-layer hyaluronic acid/ heparin nanostructure coating on stainless steel for drug-eluting stents and its use for drug delivery J. Nanosci. Nanotechnol, 6 (2006) 3163-3170
Johansson J.A., Halthur T., Herranen M., Söderberg L., Elofsson U. and Hilborn, Build-up of Collagen and Hyaluronic Acid Polyelectrolyte Multilayers, Biomacromolecules 6 (2005)1353-1359
Kang I.K., Kwon O.H., Kim M.K., Lee Y.M., Sung Y.K., Preparation and surface characterization of functional group-grafted and heparin-immobilized polyurethanes by plasma glow discharge, Biomaterials, 17 (1996) 841-847
Kang I.K., Kwon O.H., Kim M.K., Lee Y.M., Sung Y.K., In vitro blood compatibility of functional group-grafted and heparin-immobilized polyurethanes prepared by plasma glow discharge, Biomaterials, 18 (1997) 1099-1107
Kanmangne F.M., Labarre D., Serne H. and Jozefowicz M., Heparin-like activity of insoluble sulphonated polystyrene resins Part I: Influence of the surface density, nature and binding of substituted anionic groups, Biomaterials 6 (1985) 297-302
Kim SW, Feijen J, Critical Reviews in Biocompatibility, CRC Press, Boca Raton, FL. (1985) 229-260.
Lapcík L. Jr., Lapcík L., Smedt S. De, Demeester J. and Chabrecek P., Hyaluronan: Preparation, Structure, Properties, and Applications, Chem. Rev. 98, (1998) 2663-2684
Lavender M.D., Pang Z., Wallace C.S., Niklason L.E., Truskey G.A., A system for the direcr co-culture of endothelium on smooth muscle cells, Biomaterials, 26 (2005) 4642-4653
Lee H.J., Park K.D., Park H.D., Lee W.K., Han D.K., Kim S.H., Kim Y.H., Platelet and bacterial repellence on sulfonated poly(ethylene glycol)-acrylate copolymer surfaces, Colloids Surf. B, 18 (2000) 355
Lenz G.R., Martcll A.E., Metal Chelates of Mercaptosuccinic and ’-Dimercaptosuccinic Acids, lnorg. Chem., 4 (1965) 378-384
Lewis A.L., Tolhurst L.A. and Stratford P.W., Analysis of a phosphorylcholinep-based polymer coating on a coronary stent pre-and post-implantation, Biomaterials 23 (2002)1697-1706
Lin W. C., Yu D.G. and Yang M.C., pH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate: swelling kinetics and drug delivery properties, Colloids Surf. B 44 (2005) 143-151
Lin W. C., Yu D.G. and Yang M.C., Blood compatibility of thermoplastic polyurethane membrane immobilized with water-soluble chitosan/dextran sulfate, Colloids Surf. B 44 (2005) 82-92
Lin W.C., Liu T.Y., Yang M.C., Hemocompatibility of polyacrylonitrile dialysis membrane immobilized with chitosan and heparin conjugate, Biomaterials, 25 (2004) 1947-1957
Lin W.C., Tseng C.H., Yang M.C., In-Vitro Hemocompatibility Evaluation of a Thermoplastic Polyurethane Membrane with Surface-lmmobilized Water-Soluble Chitosan and Heparin, Macromol. Biosc, 5 (2005) 1013-1021
Liu T. Y., Lin W.C., Huang L.Y., Chen S. Y. and Yang M. C., Hemocompatibility and anaphylatoxin formation of protein immobilizing polyacrylonitrile hemodialysis membrane, Biomaterials 26 (2005) 1437-1444
Liu T.Y., Liao H.C., Lin C.C., Hu S.H., Chen S.Y., Biofunctional ZnO Nanorod Arrays Grown on Flexible Substrates, Langmuir 22 (2006) 5804-5809
Maisel W.H., Laskey W.K., Drug-Eluting Stents, Circulation 115 (2007) e426-e427
Neumann AW, Good RJ, Techniques of measuring contact angles. in Surface and Colloid Science-Experimental Methods, Plenum Publ., New York, 11 (1979) 31-61.
Olsson P., Sanchez J., Mollnes E.T and Riesenfeld J., On the blood compatibility of end-point immobilized heparin, J. Biomater. Sci. Polymer Edn, 11 (2000) 1261
Osterberg E., Bergstr.om K., Holmberg K., Riggs J.A., Van Alstine J.M., Schuman T.P., Burns N.L. and Harris J.M., Comparison of polysaccharide and poly(ethylene glycol) coatings for reduction of protein adsorption on polystyrene surfaces, Colloid Surf. A 77 (1993) 159
Östererg E., Bergström K., Holmberg K., Schuman T.P., Riggs J.A., Burns N.L., J.M. Alstine Van, Harris J.M., Protein-rejecting ability of surface-bound dextran in end-on and side-on configuration: Comparison to PEG, J. Biomed. Mater. Res., 29 (1995) 741-747
Park K., Kim K., Kwon I.C., Kim S.K., Lee S., Lee D.Y., Byun Y., Preparation and Characterization of Self-Assembled Nanoparticles of Heparin-Deoxycholic Acid Conjugates, Langmuir, 20, (2004) 11726-11731
Rammelt S., Illert T., Bierbaum S., Scharnweber D., Zwipp H., Schneiders W., Biomaterials, Coating of titanium implants with collagen, RGD peptide and chondroitin sulfate, 27 (2006) 5561-5571
Ranter BD, Hoffman AS, Surface grafted polymers for biomedical applications. In Syntbetic Biomedical Polymers.Concepts and Applications, Technomic, Westport, CT, (1980) 133-151
Rasulov M.M., Elikaya M.V., Zabozlaer A.G., Kuznetsov I.G., Voronkov M.G., Antiatherosclerotic effects of polysaccharide of animal origin, Bull. Exp. Biol. Med. 116 (1993) 1329-1331
Ratner BD, Surface Characterization of Biomaterials, Elsevier, Amsterdam, (1988).
Ringsdorf H., Structure and properties of pharmacologically active polymers, J. Polymer Sci. 51 (1975) 135-153
Ritger P.L., Peppas, N.A. A simple equation for description of solute release ll. Fickian and anomalous release from swellable devices, J. Control. Release, 5 (1987) 37-42
Schatz R.A., A view of vascular stents, Circulation 79 (1989) 445
Sigward U., Puel J., Mirkovitch V. and Engl N., Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty, J. Med. 316 (1987) 701
Sperling C., Houska M., Brynda E., Streller U., Werner C., In vitro hemocompatibility of albumin-heparin multilayer coatings on polyethersulfone prepared by the layer-by-layer technique, J. Biomed. Mater. Res., 76A (2006) 681-689
Sumpio B.E., Riley J.T., Dardik A., Cells in focus: endothelial cell, Int J Biochem Cell B 34 (2002) 1508-1512.
Tamada Y, Kulik EA, Ikada Y, Simple method for platelet counting, Biomaterials. 16 (1995) 259-261
Tanaka M, Motomura T, Kawada M, Anzai T, Kasori Y, Shiroya T, Shimura K, Onishi M, Mochizuki A, Blood compatible aspects of poly(2-methoxyethylacrylate) (PMEA)-relationship between protein adsorption and platelet adhesion on PMEA surface, Biomaterials 21 (2000) 1471-1481.
Thierry B., Merhi Y., Bilodeau L., Trepanier C. and Tabrizian M., Nitinol versus stainless steel stents: acute thrombogenicity study in an ex vivo porcine model, Biomaterials 23 (2002) 2997-3005
Thierry B., Winnik F.M., Merhi Y., Silver J., Tabrizian M., Bioactive Coatings of Endovascular Stents Based on Polyelectrolyte Multilayers, Biomacromolecules, 4 (2003) 1564-1571
Thomas M.R., Wainwright J. and Hancock J., J. Intervent. Cardiol. 8 (1996) 107
Wang D., He J., Rosenzweig N., Rosenzweig Z., Superparamagnetic Fe2O3 Beads-CdSe/ZnS Quantum Dots Core-Shell Nanocomposite Particles for Cell Separation, Nano. Lett., 4 (2004) 409-413
Windecker S., Mayer I., Pasquale G.D., Maier W., Dirsch O., Groot P.D., Wu Y.P., Noll G., Leskosek B., Meier B. and Hess O.M., Stent Coating With Titanium-Nitride-Oxide for Reduction of Neointimal Hyperplasia, Circulation 104(2001) 928-933
Yeh H.I., Lu S.K., Tian T.Y., Hong R.C., Lee W.H., Tsai C.H., Comparison of endothelial cells grown on different stent materials, J. Biomed. Mater. Res. 76A (2006) 835-841
Yoshioka T., Tsuru K., Hayakawa S., Osaka A., Preparation of alginic acid layers on stainless-steel substrates for biomedical applications, Biomaterials, 24 (2003) 2889
Yuan Y., Ai F., Zang X., Zhuang W., Shen J., Lin S., Polyurethane vascular catheter Polyurethane vascular catheter surface grafted with zwitterionic sulfobetaine monomer activated by ozone, Colloid. Surface. B, 35 (2004) 1-5
Zhu Y., Gao C., He T., Liu X., Shen J., Layer-by-Layer Assembly To Modify Poly(L-lactic acid) Surface toward Improving Its Cytocompatibility to Human Endothelial Cells, Biomacromolecules, 4 (2003) 446-452
林維德，Taxus藥物釋放支架系統獲得FDA許可上市，醫療器材報導，59期，2004，pp.14
洪振勛，冠狀動脈疾病治療新進展藥物塗層支架Drug-eluting Stent，藥劑通訊， 70期， 2003，pp.13-18
張根源，新世代冠狀動脈支架--Drug-eluting Stent，化工科技與商情，42期，2003，pp.19-24
組合式醫療器材範例--藥物釋放型血管支架-下，醫療器材報導55期，2003，pp.27-29
組合式醫療器材範例--藥物釋放型血管支架-上，醫療器材報導54期，2003，pp.37-40
劉定宇， PAN/PVDF易混摻血液透析膜及表面固定生物分子之滲透性質和血液相容性之探討,碩士論文,(2003)
鄭怡平，「心血管阻塞藥物釋放固定支架」核准上市，醫療器材報導，48期，2003，pp.20-21
鄭怡平，心血管阻塞藥物釋放固定支架，FDA Talk papers 2003.04.24

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