簡易檢索 / 詳目顯示

研究生: 張雅筑
Ya-Chu Chang
論文名稱: 金屬玻璃鍍層之23G醫療針具用於體內外臨床實驗研究
In-Vitro and In-Vivo Pre-Clinical Studies of Thin Film Metallic Glasses Coated on 23G Medical Needles
指導教授: 朱 瑾
Jinn. P. Chu
口試委員: 白孟宜
Meng-Yi Bai
鄭詠馨
Yung-Hsin Cheng
黃錦前
Chin-Chean Wong
學位類別: 碩士
Master
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: 2018
畢業學年度: 106
語文別: 英文
論文頁數: 97
中文關鍵詞: 金屬玻璃薄膜體內外實驗動物實驗注射針頭抗沾黏
外文關鍵詞: Thin film metallic glasses, Needle, Anti-adhesion, In-Vitro and In-Vivo studies, Animal test
相關次數: 點閱:578下載:1
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

臨床醫學上,因病情所需進行針劑治療,除在針孔處會引發細菌感染外,更容易對於皮膚及靜脈造成損傷進而影響醫療品質,此外重複穿刺靜脈,當損傷超出周圍細胞的再生能力時,也有引起血管纖維化等危機。隨著醫療進步,除了針對注射方式進行有效改善外,亦能提升現有針具之特性,因此改良注射針頭,不僅能於療程中減輕不當的損傷,降低注射過程中造成傷害之風險,亦可提升醫療品質,增進治療效果,提升注射舒適度。
根據先前所研究,金屬玻璃具高強度、低摩擦係數、耐磨耗等特性,及抗菌、抗血小板與癌細胞沾黏等良好的生物相容性質,本研究採用磁控濺鍍方式將鋯基(Zr53Cu33Al9Ta5)金屬玻璃鍍覆於注射針頭(23 G)上進行動物實驗,分別於老鼠背部皮膚及兔子靜脈血管做穿刺試驗,以模擬真實使用注射針之情形,觀察針頭沾附情況與傷口狀態、檢視組織細胞之完整性及感染等現象,並使用未鍍膜之針頭作為實驗對照組。
經動物皮膚穿次試驗後,對注射針頭進行螢光染色分析,發現鍍有金屬玻璃鍍層之針頭可降低約80%的組織細胞沾黏面積,表現出其抗沾黏之特性,另外在皮膚組織分析中,因金屬玻璃鍍層具低摩擦係數之特性,可減少針頭與組織間之摩擦,鍍有金屬玻璃鍍層的注射針頭所造成的傷口面積(0.720.48 mm2)遠小於未鍍膜針頭(1.351.92 mm2),可減少47%的損害。於動物血管穿次試驗中,亦能由內皮細胞的增生數量來反映出血管之損傷情形。整體而言,金屬玻璃鍍層不但能保護針頭在進行穿次試驗時不受磨損,亦能避免針頭對於動物體的傷害。


Generally, hypodermic needles are used for only one time. However, in some cases, they are used repeatedly. Repeated usage of needles could easily cause bacterial infections and also damage skin and vein, leading to poor healthcare quality. Therefore, improving the needle properties can not only reduce damage of tissue, but also decrease the risk of injury during the treatment.
Owing to the amorphous nature, thin film metallic glasses (TFMGs) exhibit exceptional mechanical properties, such as high strength, good wear-resistance and low coefficient of friction. In addition, TFMGs have been reported to show good biocompatibility, less adhesion to platelet and cancer cells and antibacterial properties. TFMG coating can be a potential candidate for enhancing the surface properties of medical device. In this study, Zr-based (Zr53Cu33Al9Ta5) TFMG was deposited on 23 G needles and dishes by a magnetron sputtering system. In-vitro and in-vivo tests on the mice and rabbits were conducted to simulate the practical condition of the use of needles. Afterward, the cell adhesions on needles, wound condition and cell integrity were investigated. Bare needles were also prepared as the control group for comparison.
After in-vivo test, the cells on the needles were stained and analyzed using fluorescence microscope. It revealed that cell adhesion decreases by 80% from ~6.33% for bare sample to ~1.29% for TFMG-coated sample, indicating that TFMG-coated surfaces show ability of anti-cell adhesion. Based on histological analysis, the puncture wound area decreases by 47% from ~1.35 mm2 for bare sample to ~0.72 mm2 for TFMG-coated sample. The damage of vessels can be reflected by the number of endothelial cell. Overall, a TFMG coating not only protects the needle from abrasion during the injection, but also reduces the damage of the animal tissue.

摘要 I Abstract III Acknowledgements V Content VII List of Figures IX List of Tables XIII Chapter 1 Introduction 1 Chapter 2 Background and Literature Review 3 2.1 Injection 3 2.1.1 Hypodermic needle 3 2.1.2 Unfavorable issue of hypodermic needles 4 2.1.3 Classification of Injection Routes 7 2.1.3.1 Intravenous injection 7 2.1.3.2 Intramuscular injection 8 2.1.3.3 Subcutaneous injection 8 2.1.3.4 Intradermal injection 8 2.2 Cells Adhesion 9 2.2.1 Fundamental understanding of tissue cell adhesion 9 2.2.2 Influence of surface topography on cell adhesion 11 2.3 Metallic Glass (MG) and Thin Film Metallic Glass (TFMG) 13 2.3.1 Characteristics of MGs 14 2.3.2 Unique properties of TFMG 18 2.3.3 Biomedical applications of BMG and TFMG 20 2.3.4 Material Selection 28 2.4 Magnetron Sputter Deposition 30 Chapter 3 Experimental Procedure 33 3.1 Substrate Preparation 34 3.1.1 Culture Dishes and Needle Preparations 34 3.1.2 TFMG Deposition 34 3.2 Characterizations of TFMG 36 3.2.1 Crystallographic Analysis 36 3.2.2 Thermal analysis 37 3.2.3 Chemical Analysis 37 3.2.4 Surface Roughness Observation 38 3.3 In Vitro Tests 38 3.3.1 Cell Culture 38 3.3.2 Cell Viability Analysis 40 3.3.3 Coagulation assays 41 3.4 In Vivo Tests 41 3.4.1 Animal Preparations 41 3.4.1.1 Rabbit 41 3.4.1.2 Mice 41 3.4.2 Intravenous and Subcutaneous Injection 42 3.4.3 Paraffin Sections Preparation 43 3.4.4 Adhesion Area Measurement 43 Chapter 4 Results and Discussion 45 4.1 TFMG Properties 45 4.2 In Vitro Tests 47 4.2.1 Cell Morphology Observation 47 4.2.2 Cell viability 49 4.2.3 Coagulation assays 51 4.3 In Vivo Tests for Intravenous Injection 52 4.3.1 Surface Morphology Observation of Injection Needles 52 4.3.2 Cell Adhesion Area Analysis 61 4.3.3 Histopathology Analysis 65 4.4 In Vivo Tests for Subcutaneous Injection 70 4.4.1 Surface Morphology Observation of Injection Needles 70 4.4.2 Adhesion area analysis 77 4.4.3 Sticking Analysis 81 4.4.4 Histopathology Analysis 82 4.5 Discussion 87 Chapter 5 Conclusions and Future Works 91 5.1 Conclusions 91 5.2 Future Works 92 References 93 Appendix 97

[1] L. Schneider, L. Peck, J. Melvin, Penetration characteristics of hypodermic needles in skin and muscle tissue. Phase I (Appendices BE). Final report. Highway Safety Research Institute, Ann Arbor, MI, DOI (1978).
[2] H.S. Gill, M.R. Prausnitz, Does Needle Size Matter?, Journal of diabetes science and technology (Online), 1 (2007) 725-729.
[3] J.P. Chu, C.-C. Yu, Y. Tanatsugu, M. Yasuzawa, Y.-L. Shen, Non-stick syringe needles: Beneficial effects of thin film metallic glass coating, Scientific Reports, 6 (2016) 31847.
[4] J.P. Chu, T.-Y. Liu, C.-L. Li, C.-H. Wang, J.S.C. Jang, M.-J. Chen, S.-H. Chang, W.-C. Huang, Fabrication and characterizations of thin film metallic glasses: Antibacterial property and durability study for medical application, Thin Solid Films, 561 (2014) 102-107.
[5] C.-H. Chang, C.-L. Li, C.-C. Yu, Y.-L. Chen, S. Chyntara, J.P. Chu, M.-J. Chen, S.-H. Chang, Beneficial effects of thin film metallic glass coating in reducing adhesion of platelet and cancer cells: Clinical testing, Surface and Coatings Technology, 344 (2018) 312-321.
[6] R.E. Kravetz, Hypodermic Syringe, The American Journal Of Gastroenterology, 100 (2005) 2614.
[7] A.M. Hauri, G.L. Armstrong, Y.J. Hutin, The global burden of disease attributable to contaminated injections given in health care settings, International journal of STD & AIDS, 15 (2004) 7-16.
[8] S. Ojala, H.-S. Kaukkila, Injektionanto lihakseen–millä, miten ja mihin pistät, Sairaanhoitaja, 81 (2008) 14-19.
[9] AstraZeneca, https://www.astrazeneca.com/.
[10] I. Gurappa, Development of appropriate thickness ceramic coatings on 316 L stainless steel for biomedical applications, Surface and Coatings Technology, 161 (2002) 70-78.
[11] R. Köster, D. Vieluf, M. Kiehn, M. Sommerauer, J. Kähler, S. Baldus, T. Meinertz, C.W. Hamm, Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis, The Lancet, 356 (2000) 1895-1897.
[12] H. Lee, C.-K. Yao, J.-D. Liao, P.-L. Shao, M.-H.N. Thi, Y.-H. Lin, Y.-D. Juang, Annealed thin-film zirconia coating adhered on 316L stainless steel as a bio-inert indwelling needle, Materials & Design, 88 (2015) 651-658.
[13] G.R. Doyle, J.A. McCutcheon, Clinical Procedures for Safer Patient Care, Campus Manitoba2016.
[14] J.-f. Jin, L.-l. Zhu, M. Chen, H.-m. Xu, H.-f. Wang, X.-q. Feng, X.-p. Zhu, Q. Zhou, The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection, Patient preference and adherence, 9 (2015) 923-942.
[15] L.H. Nicoll, A. Hesby, Intramuscular injection: An integrative research review and guideline for evidence-based practice, Applied Nursing Research, 15 (2002) 149-162.
[16] T. Carol, L. Carol, L. Priscilla, Fundamentals of nursing: The art and science of nursing care, JB Lippincott Philadelphia. Pag, DOI (1993) 29-31.
[17] A.A. Khalili, M.R. Ahmad, A review of cell adhesion studies for biomedical and biological applications, International journal of molecular sciences, 16 (2015) 18149-18184.
[18] M. Dembo, D. Torney, K. Saxman, D. Hammer, The reaction-limited kinetics of membrane-to-surface adhesion and detachment, Proc. R. Soc. Lond. B, 234 (1988) 55-83.
[19] Y. Shen, M. Nakajima, S. Kojima, M. Homma, M. Kojima, T. Fukuda, Single cell adhesion force measurement for cell viability identification using an AFM cantilever-based micro putter, Measurement Science and Technology, 22 (2011) 115802.
[20] K. Ley, C. Laudanna, M.I. Cybulsky, S. Nourshargh, Getting to the site of inflammation: the leukocyte adhesion cascade updated, Nature Reviews Immunology, 7 (2007) 678.
[21] K.V. Honn, D.G. Tang, Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix, Cancer and Metastasis Reviews, 11 (1992) 353-375.
[22] T. Naganuma, The relationship between cell adhesion force activation on nano/micro-topographical surfaces and temporal dependence of cell morphology, Nanoscale, 9 (2017) 13171-13186.
[23] W. Klement Jun, R.H. Willens, P.O.L. Duwez, Non-crystalline Structure in Solidified Gold–Silicon Alloys, Nature, 187 (1960) 869.
[24] W.H. Wang, C. Dong, C.H. Shek, Bulk metallic glasses, Materials Science and Engineering: R: Reports, 44 (2004) 45-89.
[25] S. Kavesh, Principles of Fabrication(of Metallic Glasses), Metallic Glasses. ASM, Metals Park, Ohio. 1978, 36-73, DOI (1978).
[26] H.S. Chen, Thermodynamic considerations on the formation and stability of metallic glasses, Acta Metallurgica, 22 (1974) 1505-1511.
[27] W.L. Johnson, Bulk Glass-Forming Metallic Alloys: Science and Technology, MRS Bulletin, 24 (1999) 42-56.
[28] H.-W. Jeong, S. Hata, A. Shimokohbe, Micro-forming of thin film metallic glass by local laser heating, Micro Electro Mechanical Systems, 2002. The Fifteenth IEEE International Conference on, IEEE, 2002, pp. 372-375.
[29] A. Inoue, A. Takeuchi, Recent development and application products of bulk glassy alloys, Acta Materialia, 59 (2011) 2243-2267.
[30] W.L. Johnson, Thermodynamic and kinetic aspects of the crystal to glass transformation in metallic materials, Progress in Materials Science, 30 (1986) 81-134.
[31] M.F. Ashby, A.L. Greer, Metallic glasses as structural materials, Scripta Materialia, 54 (2006) 321-326.
[32] P.-S. Chen, H.-W. Chen, J.-G. Duh, J.-W. Lee, J.S.-C. Jang, Characterization of mechanical properties and adhesion of Ta–Zr–Cu–Al–Ag thin film metallic glasses, Surface and Coatings Technology, 231 (2013) 332-336.
[33] C.-Y. Chuang, J.-W. Lee, C.-L. Li, J.P. Chu, Mechanical properties study of a magnetron-sputtered Zr-based thin film metallic glass, Surface and Coatings Technology, 215 (2013) 312-321.
[34] J. Hee-Won, S. Hata, A. Shimokohbe, Microforming of three-dimensional microstructures from thin-film metallic glass, Journal of Microelectromechanical Systems, 12 (2003) 42-52.
[35] A. Inoue, Stabilization of metallic supercooled liquid and bulk amorphous alloys, Acta Materialia, 48 (2000) 279-306.
[36] J.C. Wataha, C. Hanks, R.G. Craig, In vitro effect of metal ions on cellular metabolism and the correlation between these effects and the uptake of the ions, Journal of Biomedical Materials Research Part A, 28 (1994) 427-433.
[37] S. Hiromoto, A.P. Tsai, M. Sumita, T. Hanawa, Effect of chloride ion on the anodic polarization behavior of the Zr65Al7.5Ni10Cu17.5 amorphous alloy in phosphate buffered solution, Corrosion Science, 42 (2000) 1651-1660.
[38] L. Liu, C.L. Qiu, Q. Chen, S.M. Zhang, Corrosion behavior of Zr-based bulk metallic glasses in different artificial body fluids, Journal of Alloys and Compounds, 425 (2006) 268-273.
[39] F. Hadjoub, W. Metiri, A. Doghmane, Z. Hadjoub, Bulk metallic glass matrix composite for good biocompatibility, IOP Conference Series: Materials Science and Engineering, 28 (2012) 012038.
[40] D.R. Knittel, A. Bronson, Pitting Corrosion on Zirconium—A Review, CORROSION, 40 (1984) 9-14.
[41] J.P. Chu, J.S.C. Jang, J.C. Huang, H.S. Chou, Y. Yang, J.C. Ye, Y.C. Wang, J.W. Lee, F.X. Liu, P.K. Liaw, Y.C. Chen, C.M. Lee, C.L. Li, C. Rullyani, Thin film metallic glasses: Unique properties and potential applications, Thin Solid Films, 520 (2012) 5097-5122.
[42] J.P. Chu, C.M. Lee, R.T. Huang, P.K. Liaw, Zr-based glass-forming film for fatigue-property improvements of 316L stainless steel: Annealing effects, Surface and Coatings Technology, 205 (2011) 4030-4034.
[43] J.P. Chu, C.-Y. Wang, L.J. Chen, Q. Chen, Annealing-induced amorphization in a sputtered glass-forming film: In-situ transmission electron microscopy observation, Surface and Coatings Technology, 205 (2011) 2914-2918.
[44] F.X. Liu, F.Q. Yang, Y.F. Gao, W.H. Jiang, Y.F. Guan, P.D. Rack, O. Sergic, P.K. Liaw, Micro-scratch study of a magnetron-sputtered Zr-based metallic-glass film, Surface and Coatings Technology, 203 (2009) 3480-3484.
[45] B. Zberg, P.J. Uggowitzer, J.F. Löffler, MgZnCa glasses without clinically observable hydrogen evolution for biodegradable implants, Nature Materials, 8 (2009) 887.
[46] P.-T. Chiang, G.-J. Chen, S.-R. Jian, Y.-H. Shih, J.S.-C. Jang, C.-H. Lai, Surface Antimicrobial Effects of Zr61Al7.5Ni10Cu17.5Si4 Thin Film Metallic Glasses on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Candida albicans, Fooyin Journal of Health Sciences, 2 (2010) 12-20.
[47] R.J. Narayan, Nanostructured diamondlike carbon thin films for medical applications, Materials Science and Engineering: C, 25 (2005) 405-416.
[48] C.-L. Li, J.-C. Chang, B.-S. Lou, J.-W. Lee, J.P. Chu, Fabrication of W-Zr-Si thin film metallic glasses and the influence of post-annealing treatment, Journal of Non-Crystalline Solids, 482 (2018) 170-176.
[49] Z. Li, C. Zhang, L. Liu, Wear behavior and corrosion properties of Fe-based thin film metallic glasses, Journal of Alloys and Compounds, 650 (2015) 127-135.
[50] D.M. Mattox, Handbook of Physical Vapor Deposition (PVD) Processing, Film Formation, Adhesion, Surface Preparation and Contamination Control, 1998, Google Scholar, DOI 343.
[51] R.A. Surmenev, A review of plasma-assisted methods for calcium phosphate-based coatings fabrication, Surface and Coatings Technology, 206 (2012) 2035-2056.
[52] P.J. Kelly, R.D. Arnell, Magnetron sputtering: a review of recent developments and applications, Vacuum, 56 (2000) 159-172.
[53] Y.B. Wang, Y.F. Zheng, S.C. Wei, M. Li, In vitro study on Zr‐based bulk metallic glasses as potential biomaterials, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 96B (2011) 34-46.
[54] B.I. Tarnowski, F.G. Spinale, J.H. Nicholson, DAPI as a Useful Stain for Nuclear Quantitation, Biotechnic & Histochemistry, 66 (1991) 296-302.
[55] S.M. Schwartz, C.C. Haudenschild, E. Eddy, Endothelial regneration. I. Quantitative analysis of initial stages of endothelial regeneration in rat aortic intima, Laboratory investigation; a journal of technical methods and pathology, 38 (1978) 568-580.
[56] M.R. Cesarone, G. Belcaro, L. Pellegrini, A. Ledda, G. Vinciguerra, A. Ricci, G. Gizzi, E. Ippolito, F. Fano, M. Dugall, Circulating endothelial cells in venous blood as a marker of endothelial damage in chronic venous insufficiency: improvement with venoruton, Journal of cardiovascular pharmacology and therapeutics, 11 (2006) 93-99.
[57] 曾永喆, Effects of thin film metallic glass coating on skin grafting using a dermatome blade, 國立台灣科技大學, DOI (2015).

無法下載圖示 全文公開日期 2023/08/02 (校內網路)
全文公開日期 本全文未授權公開 (校外網路)
全文公開日期 本全文未授權公開 (國家圖書館:臺灣博碩士論文系統)
QR CODE