跳到主要內容

臺灣博碩士論文加值系統

(3.236.84.188) 您好!臺灣時間:2021/08/03 08:13
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:揭小鳳
研究生(外文):Hsiao-FengChieh
論文名稱:運用二維自組裝單分子層模型與三維細胞-膠原蛋白模型探討間質幹細胞與微觀環境之交互作用
論文名稱(外文):Using 2D self-assembled monolayers and 3D cell-collagen construct models to study interactions between mesenchymal stromal cells and microenvironments in vitro
指導教授:廖峻德廖峻德引用關係
指導教授(外文):Jiunn-Der Liao
學位類別:博士
校院名稱:國立成功大學
系所名稱:材料科學及工程學系碩博士班
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:120
中文關鍵詞:微觀環境間質幹細胞表面化學機械性質
外文關鍵詞:microenvironmentmesenchymal stromal cellssurface chemistrymechanical properties
相關次數:
  • 被引用被引用:0
  • 點閱點閱:122
  • 評分評分:
  • 下載下載:7
  • 收藏至我的研究室書目清單書目收藏:0
生物組織的巨觀環境和細胞周圍的微觀環境已知能提供幹細胞各種不同的刺激,藉由訊號傳遞改變細胞行為。首先,本研究主運用自組裝單分子層特徵的二維表面模型來探討表面化學對間質幹細胞的影響。在探討表面化學對間質幹細胞的研究中,我們使用四種具相近碳鏈長但不同尾端官能基(–CH3, –COOH, –OH, –NH2)的自組裝單分子層,並檢視其物理化學及機械性質。首先,本研究運用一新的奈米壓痕技術測量自組裝單分子層的機械性質。結果顯示其奈米機械性質些微的差異與自組裝分子層本身的排列整齊度有關。且此奈米等級的差異不足以讓細胞機械感測受器分別其差異、影響細胞的行為。因此,本研究證實自組裝分子層模型為一探究表面化學在蛋白質吸附行為及細胞功能影響的極佳平台。本研究指出表面的化學性質在蛋白質吸附過程中,會因彼此競爭效應改變貼附蛋白質的構形,進而影響貼附蛋白質的細胞鍵結區露出量。此外,本研究指出在短期培養時,不同的表面化學特性會導致不同吸附蛋白質的細胞鍵結區露出量,進而影響到脂肪幹細胞的黏附、伸展、遷移模式、分化趨勢。但表面化學性質對細胞的影響會隨著培養時間遞減。
由二維表面模型研究中得到因表面化學性質差異造成吸附蛋白質構形差異進而導致間質幹細胞不同表現的結論,本研究運用骨髓幹細胞-第一型膠原蛋白混合物模型探討間質幹細胞和細胞外基質之間的交互作用。研究探討細胞濃度與膠原蛋白濃度對細胞-膠原蛋白混合物在收縮動力學和機械性質表現的影響。並在培養兩週後,將由incremental stress-relaxation test得到的應力應變曲線套入由MATLAB程式撰寫的類線性黏彈模型中得到細胞-膠原蛋白混合物的黏彈性質。研究結果顯示當細胞-膠原蛋白混合物具有較高的初始細胞濃度或是較低的初始膠原蛋白濃度時,其會呈現較快的收縮行為、較高的極限應力、較佳的彈性和較差的應力鬆弛行為。
本研究完整鑑定二維表面模型和三維細胞-膠原蛋白混合物模型的適用性並加以運用於探討間質幹細胞與周圍微環境的交互作用。本研究結果希望能夠提供在未來組織工程應用上當有特定需求時用以評估支架材料選擇或是植入物表面修飾一有用的研究平台及方法。

Microenvironments provide cues to stem cells and induce signals to direct their fate. In this study, we used self-assembled monolayers (SAMs), a 2D model system, to investigate the effect of surface chemistry on cell functions of mesenchymal stromal cells (MSCs). SAMs with various terminated functional groups (–CH3, –COOH, –OH, –NH2) were used to estimate the influence of surface chemistry on protein adsorption and cell functions. The features of the SAMs adsorbed on Au were characterized using physicochemical and depth-sensing nano-indentation methods. The ordering of various tail-group terminated SAMs on Au was associated with the rate of harmonic contact stiffness of the SAM molecules along with the measured displacement. Results of mechanical properties showed that the slight difference among SAMs/Au is not able to induce cellular mechano-sensitive responses. Hence, this study provided evidences that SAMs model system is a perfect plate for estimating the effect of surface chemistry on protein adsorption and cell functions. In addition, our findings showed that surface-chemistry induced different level of exposure of cell-binding domains of adsorbed proteins may direct cell functions of ADSCs, including cell attachment, cell shape, migration pattern, and differentiation potential in short-term incubation.
Based on the results that conformational changes of adsorbed proteins regulated cell functions of MSCs, a cell-collagen construct 3D model system was used to assess the interaction between cell and extracellular matrix. Effects of cell concentration and collagen concentration on the contraction kinetics and mechanical properties of bone marrow stromal cells seeded collagen lattices were estimated. Incremental stress-relaxation tests were carried out after a 2-week incubation to obtain the stress-strain profiles, which were subsequently assessed in a quasilinear viscoelastic model. Results showed that constructs seeded with a higher initial cell concentration or lower initial collagen concentration exhibited faster contraction, higher ultimate stress, and superior elasticity and reduced relaxation behavior.
In this study, 2D SAMs model system and 3D cell-collagen construct model system were fully validated and applied to assess the interactions between mesenchymal stromal cells and surrounding microenvironments. We hope these findings may provide researchers useful investigation plates to estimate materials of scaffold and surface modification of implants for further specific application on tissue engineering.

ABSTRACT.................................................I
中文摘要..................................................III
誌謝......................................................V
TABLE OF CONTENTS........................................VI
LIST OF TABLES...........................................X
LIST OF FIGURES..........................................XI
CHAPTER I.................................................1
INTRODUCTION..............................................1
1.1 BACKGROUND............................................1
1.2 OBJECTIVES............................................3
CHAPTER II................................................5
RELATED LITERATURE........................................5
2.1 THERAPEUTIC APPLICATION OF STEM CELLS IN TISSUE ENGINEERING...............................................5
2.1.1 Mesenchymal stem cells sources......................5
2.1.2 Biomaterials as instructive extracellular microenvironments.........................................6
2.2 ENGINEERED TWO-DIMENSIONAL SUBSTRATES FOR DIRECTING STEM CELL BEHAVIORS.......................................8
2.2.1 Surface properties..................................9
2.2.2 Mechanical properties..............................10
2.2.3 2D SAMs model for investigating effects of surface chemistry on cellular responses..........................11
2.3 ENGINEERED THREE-DIMENSIONAL MATRICES FOR DIRECTING STEM CELL BEHAVIORS......................................13
2.3.1 Biomimetic approach................................13
2.3.2 3D cell-collagen construct model system............14
a. Contraction behaviors and mechanical properties.......14
b. BMSCs-collagen construct model for tendon tissue engineering application..................................15
CHAPTER III..............................................17
MATERIALS AND METHODS....................................17
3.1 EXPERIMENTAL SECTION I: 2D SAMS MODELED SURFACES.....17
3.1.1 Formation of self-assembled monolayers.............17
3.1.2 Physicochemical characterization...................18
a. High resolution X-ray photoelectron spectroscopy (HRXPS)..................................................18
b. Ellipsometry..........................................18
c. Contact angle goniometry..............................18
d. Atomic force microscopy (AFM).........................19
3.1.3 Nano-mechanical measurement........................19
a. Loading process.......................................19
b. Define the “SAMs” zone................................20
3.1.4 Exposed cell-binding domains of adsorbed proteins..22
3.1.5 Cell functions on SAMs modified surfaces...........23
a. Isolation and culture of ADSCs........................23
b. Scanning electron microscope..........................24
c. Cell migration observed by time-lapse microscopy......25
d. MTS Assay.............................................25
e. Cytoskeleton reorganization and extracellular matrix protein formation........................................26
f. RNA isolation and real-time PCR.......................27
3.2 EXPERIMENTAL SECTION II: 3D BMSCS-COLLAGEN MATRICES..29
3.2.1 Preparation of 3D BMSCs-collagen matrices..........29
a. Harvesting and culturing BMSCs........................29
b. Preparation of BMSCs populated collagen gel ring......30
3.2.2 Quantification of gel contraction..................31
3.2.3 Staining of BMSCs populated collagen gels for confocal microscopy......................................31
3.2.4 Mechanical measurement of cell-collagen constructs...............................................32
a. Incremental stress-relaxation test....................32
b. Quasilinear viscoelastic theory.......................34
3.3 STATISTICAL ANALYSIS.................................36
CHAPTER IV...............................................37
EXPOSURE OF CELL-BINDING DOMAINS OF ADSORBED PROTEINS AND CELL FUNCTIONS OF ADSCS ON VARIOUS SAMS MODIFIED SURFACES.................................................37
4.1 BACKGROUND...........................................37
4.2 RESULTS..............................................40
4.2.1 Physicochemical properties of SAMs chemically adsorbed on Au...........................................40
4.2.2 Nano-mechanical property with respect to molecular arrangement of SAMs on Au................................43
4.2.3 Cell adhesion and spreading........................46
4.2.4 Cell metabolic activity............................46
4.2.5 Exposed cell-binding domains of adsorbed proteins on SAMs/Au..................................................48
4.2.6 Cytoskeleton organization and extracellular matrix secretion................................................51
4.2.7 Cell migration.....................................52
4.2.8 Cell differentiation potential.....................59
4.3 DISCUSSION...........................................61
4.3.1 Physicochemical characteristics and mechanical properties of SAMs.......................................61
4.3.2 Cell shape and cytoskeleton organization...........62
4.3.3 Mechanism mediating cell adhesion of ADSCs on SAMs/Au..................................................64
4.3.4 Migratory behavior.................................67
4.3.5 Cell differentiation potential.....................70
CHAPTER V................................................75
EFFECTS OF CELL CONCENTRATION AND COLLAGEN CONCENTRATION ON CONTRACTION KINETICS AND MECHANICAL PROPERTIES IN A BONE MARROW STROMAL CELL-COLLAGEN CONSTRUCT................................................75
5.1BACKGROUND............................................75
5.2 RESULTS..............................................76
5.2.1 Cell morphology and alignment......................76
5.2.2 Contraction rate...................................78
5.2.3 Mechanical properties..............................79
5.3 DISCUSSION...........................................85
5.3.1 Cell alignment.....................................85
5.3.2 Contraction behavior...............................86
5.3.3 Mechanical properties..............................86
6.3.4 Potentials of cell-collagen constructs for tendon healing..................................................89
CHAPTER VI...............................................91
CONCLUSION...............................................91
REFERENCES...............................................94
APPENDIX................................................108
A. THE EFFECTS OF BONE MARROW STROMAL CELL TRANSPLANTS ON TENDON HEALING EX VIVO..................................108
A.1 MATERIALS AND METHODS...............................109
A.1.1 Bone Marrow Stromal Cell Harvest..................109
A.1.2 Preparation of Cell-Seeded Collagen Gel...........110
A.1.3 Tendon Repair with Implant........................111
A.1.4 Repaired Tendon Culture...........................112
A.1.5 Biomechanical Testing.............................113
A.1.6 Statistical Analysis..............................114
A.2 RESULTS.............................................115
A.3 DISCUSSION..........................................117


1.R. Langer, and J. P. Vacanti. Tissue engineering. Science 260(5110):920-926, 1993.
2.L. G. Griffith, and G. Naughton. Tissue engineering--current challenges and expanding opportunities. Science 295(5557):1009-1014, 2002.
3.C. R. Jenney, K. M. DeFife, E. Colton, and J. M. Anderson. Human monocyte/macrophage adhesion, macrophage motility, and IL-4-induced foreign body giant cell formation on silane-modified surfaces in vitro. Student Research Award in the Master's Degree Candidate Category, 24th Annual Meeting of the Society for Biomaterials, San Diego, CA, April 22-26, 1998. Journal of Biomedical Materials Research 41(2):171-184, 1998.
4.K. Webb, V. Hlady, and P. A. Tresco. Relationships among cell attachment, spreading, cytoskeletal organization, and migration rate for anchorage-dependent cells on model surfaces. Journal of Biomedical Materials Research 49(3):362-368, 2000.
5.Y. Ito. Surface micropatterning to regulate cell functions. Biomaterials 20(23-24):2333-2342, 1999.
6.R. Kapur, and A. S. Rudolph. Cellular and cytoskeleton morphology and strength of adhesion of cells on self-assembled monolayers of organosilanes. Experimental Cell Research 244(1):275-285, 1998.
7.M. Sittinger, J. Bujia, N. Rotter, D. Reitzel, W. W. Minuth, and G. R. Burmester. Tissue engineering and autologous transplant formation: practical approaches with resorbable biomaterials and new cell culture techniques. Biomaterials 17(3):237-242, 1996.
8.L. Moroni, J. R. de Wijn, and C. A. van Blitterswijk. Integrating novel technologies to fabricate smart scaffolds. Journal of Biomaterials Science, Polymer Edition 19(5):543-572, 2008.
9.G. Cossu, and P. Bianco. Mesoangioblasts--vascular progenitors for extravascular mesodermal tissues. Current Opinion in Genetics & Development 13(5):537-542, 2003.
10.R. D. McKay. Stem cell biology and neurodegenerative disease. Philosophical Transactions of the Royal Society B: Biological Sciences 359(1445):851-856, 2004.
11.N. S. Hwang, S. Varghese, and J. Elisseeff. Controlled differentiation of stem cells. Advanced Drug Delivery Reviews 60(2):199-214, 2008.
12.M. F. Pittenger, A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. D. Mosca, M. A. Moorman, D. W. Simonetti, S. Craig, and D. R. Marshak. Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143-147, 1999.
13.S. Goldman. Stem and progenitor cell-based therapy of the human central nervous system. Nat Biotechnol 23(7):862-871, 2005.
14.R. Galli, A. Gritti, and A. L. Vescovi. Adult neural stem cells. Methods Mol Biol 438:67-84, 2008.
15.P. A. Zuk, M. Zhu, H. Mizuno, J. Huang, J. W. Futrell, A. J. Katz, P. Benhaim, H. P. Lorenz, and M. H. Hedrick. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Engineering 7(2):211-228, 2001.
16.S. P. Bruder, K. H. Kraus, V. M. Goldberg, and S. Kadiyala. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. Journal of Bone and Joint Surgery - American Volume 80(7):985-996, 1998.
17.T. Niedzwiedzki, Z. Dabrowski, H. Miszta, and M. Pawlikowski. Bone healing after bone marrow stromal cell transplantation to the bone defect. Biomaterials 14(2):115-121, 1993.
18.T. Yoshikawa, H. Ohgushi, and S. Tamai. Immediate bone forming capability of prefabricated osteogenic hydroxyapatite. Journal of Biomedical Materials Research 32(3):481-492, 1996.
19.A. J. Engler, S. Sen, H. L. Sweeney, and D. E. Discher. Matrix elasticity directs stem cell lineage specification. Cell 126(4):677-689, 2006.
20.D. Bosnakovski, M. Mizuno, G. Kim, S. Takagi, M. Okumura, and T. Fujinaga. Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: influence of collagen type II extracellular matrix on MSC chondrogenesis. Biotechnology and Bioengineering 93(6):1152-1163, 2006.
21.C. Chung, and J. A. Burdick. Engineering cartilage tissue. Advanced Drug Delivery Reviews 60(2):243-262, 2008.
22.N. Datta, Q. P. Pham, U. Sharma, V. I. Sikavitsas, J. A. Jansen, and A. G. Mikos. In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation. Proceedings of the National Academy of Sciences of the United States of America 103(8):2488-2493, 2006.
23.C. F. Chang, M. W. Lee, P. Y. Kuo, Y. J. Wang, Y. H. Tu, and S. C. Hung. Three-dimensional collagen fiber remodeling by mesenchymal stem cells requires the integrin-matrix interaction. Journal of Biomedical Materials Research Part A 80(2):466-474, 2007.
24.C. R. Nuttelman, M. C. Tripodi, and K. S. Anseth. Synthetic hydrogel niches that promote hMSC viability. Matrix Biology 24(3):208-218, 2005.
25.S. Varghese, N. S. Hwang, A. C. Canver, P. Theprungsirikul, D. W. Lin, and J. Elisseeff. Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. Matrix Biology 27(1):12-21, 2008.
26.B. G. Keselowsky, D. M. Collard, and A. J. Garcia. Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 102(17):5953-5957, 2005.
27.A. J. Garcia, M. D. Vega, and D. Boettiger. Modulation of cell proliferation and differentiation through substrate-dependent changes in fibronectin conformation. Molecular Biology of the Cell 10(3):785-798, 1999.
28.A. Baszkin, and D. J. Lyman. The interaction of plasma proteins with polymers. I. Relationship between polymer surface energy and protein adsorption/desorption. Journal of Biomedical Materials Research 14(4):393-403, 1980.
29.S. B. Kennedy, N. R. Washburn, C. G. Simon, Jr., and E. J. Amis. Combinatorial screen of the effect of surface energy on fibronectin-mediated osteoblast adhesion, spreading and proliferation. Biomaterials 27(20):3817-3824, 2006.
30.W. L. Murphy, S. Hsiong, T. P. Richardson, C. A. Simmons, and D. J. Mooney. Effects of a bone-like mineral film on phenotype of adult human mesenchymal stem cells in vitro. Biomaterials 26(3):303-310, 2005.
31.W. G. Brodbeck, Y. Nakayama, T. Matsuda, E. Colton, N. P. Ziats, and J. M. Anderson. Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro. Cytokine 18(6):311-319, 2002.
32.D. S. Benoit, M. P. Schwartz, A. R. Durney, and K. S. Anseth. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nature Materials 7(10):816-823, 2008.
33.L. Guo, N. Kawazoe, Y. Fan, Y. Ito, J. Tanaka, T. Tateishi, X. Zhang, and G. Chen. Chondrogenic differentiation of human mesenchymal stem cells on photoreactive polymer-modified surfaces. Biomaterials 29(1):23-32, 2008.
34.J. M. Curran, R. Chen, and J. A. Hunt. Controlling the phenotype and function of mesenchymal stem cells in vitro by adhesion to silane-modified clean glass surfaces. Biomaterials 26(34):7057-7067, 2005.
35.J. M. Curran, R. Chen, and J. A. Hunt. The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrate. Biomaterials 27(27):4783-4793, 2006.
36.D. E. Ingber. Cellular mechanotransduction: putting all the pieces together again. The Journal of the Federation of American Societies for Experimental Biology 20(7):811-827, 2006.
37.C. S. Chen, M. Mrksich, S. Huang, G. M. Whitesides, and D. E. Ingber. Geometric control of cell life and death. Science 276(5317):1425-1428, 1997.
38.C. B. Khatiwala, P. D. Kim, S. R. Peyton, and A. J. Putnam. ECM compliance regulates osteogenesis by influencing MAPK signaling downstream of RhoA and ROCK. Journal of Bone and Mineral Research 24(5):886-898, 2009.
39.M. Singh, C. Berkland, and M. S. Detamore. Strategies and applications for incorporating physical and chemical signal gradients in tissue engineering. Tissue Engineering Part B: Review 14(4):341-366, 2008.
40.C. N. Sukenik, N. Balachander, L. A. Culp, K. Lewandowska, and K. Merritt. Modulation of cell adhesion by modification of titanium surfaces with covalently attached self-assembled monolayers. Journal of Biomedical Materials Research 24(10):1307-1323, 1990.
41.M. Mrksich, C. S. Chen, Y. Xia, L. E. Dike, D. E. Ingber, and G. M. Whitesides. Controlling cell attachment on contoured surfaces with self-assembled monolayers of alkanethiolates on gold. Proceedings of the National Academy of Sciences of the United States of America 93(20):10775-10778, 1996.
42.N. Faucheux, R. Schweiss, K. Lutzow, C. Werner, and T. Groth. Self-assembled monolayers with different terminating groups as model substrates for cell adhesion studies. Biomaterials 25(14):2721-2730, 2004.
43.L. A. Culp, and C. N. Sukenik. Cell type-specific modulation of fibronectin adhesion functions on chemically-derivatized self-assembled monolayers. Journal of Biomaterials Science, Polymer Edition 9(11):1161-1176, 1998.
44.C. H. Thomas, C. D. McFarland, M. L. Jenkins, A. Rezania, J. G. Steele, and K. E. Healy. The role of vitronectin in the attachment and spatial distribution of bone-derived cells on materials with patterned surface chemistry. Journal of Biomedical Materials Research 37(1):81-93, 1997.
45.K. B. McClary, T. Ugarova, and D. W. Grainger. Modulating fibroblast adhesion, spreading, and proliferation using self-assembled monolayer films of alkylthiolates on gold. Journal of Biomedical Materials Research 50(3):428-439, 2000.
46.C. D. Tidwell, S. I. Ertel, B. D. Ratner, B. J. Tarasevich, S. Atre, and D. L. Allara. Endothelial cell growth and protein adsorption on terminally functionalized, self-assembled monolayers of alkanethiolates on gold. Langmuir 13(13):3404-3413, 1997.
47.W. Senaratne, L. Andruzzi, and C. K. Ober. Self-assembled monolayers and polymer brushes in biotechnology: current applications and future perspectives. Biomacromolecules 6(5):2427-2448, 2005.
48.C. A. Scotchford, C. P. Gilmore, E. Cooper, G. J. Leggett, and S. Downes. Protein adsorption and human osteoblast-like cell attachment and growth on alkylthiol on gold self-assembled monolayers. Journal of Biomedical Materials Research 59(1):84-99, 2002.
49.H. F. Chieh, F. C. Su, J. D. Liao, S. C. Lin, C. W. Chang, and M. R. Shen. Attachment and morphology of adipose-derived stromal cells and exposure of cell-binding domains of adsorbed proteins on various self-assembled monolayers. Soft Matter 7(8):3808-3817, 2011.
50.C. W. Chang, and J. D. Liao. Nano-indentation at the surface contact level: applying a harmonic frequency for measuring contact stiffness of self-assembled monolayers adsorbed on Au. Nanotechnology 19(31), 2008.
51.Y. Arima, and H. Iwata. Effect of wettability and surface functional groups on protein adsorption and cell adhesion using well-defined mixed self-assembled monolayers. Biomaterials 28(20):3074-3082, 2007.
52.C. C. Barrias, M. C. L. Martins, G. Almeida-Porada, M. A. Barbosa, and P. L. Granja. The correlation between the adsorption of adhesive proteins and cell behaviour on hydroxyl-methyl mixed self-assembled monolayers. Biomaterials 30(3):307-316, 2009.
53.M. A. Lan, C. A. Gersbach, K. E. Michael, B. G. Keselowsky, and A. J. Garcia. Myoblast proliferation and differentiation on fibronectin-coated self assembled monolayers presenting different surface chemistries. Biomaterials 26(22):4523-4531, 2005.
54.B. G. Keselowsky, D. M. Collard, and A. J. Garcia. Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. Biomaterials 25(28):5947-5954, 2004.
55.Y. J. Ren, H. Zhang, H. Huang, X. M. Wang, Z. Y. Zhou, F. Z. Cui, and Y. H. An. In vitro behavior of neural stem cells in response to different chemical functional groups. Biomaterials 30(6):1036-1044, 2009.
56.J. E. Phillips, T. A. Petrie, F. P. Creighton, and A. J. Garcia. Human mesenchymal stem cell differentiation on self-assembled monolayers presenting different surface chemistries. Acta Biomaterialia 6(1):12-20, 2010.
57.J. A. Burdick, and G. Vunjak-Novakovic. Engineered microenvironments for controlled stem cell differentiation. Tissue Engineering Part A 15(2):205-219, 2009.
58.C. Frank, D. Amiel, S. L. Woo, and W. Akeson. Normal ligament properties and ligament healing. Clinical Orthopaedics and Related Research (196):15-25, 1985.
59.A. I. Caplan. The mesengenic process. Clinics in Plastic Surgery 21(3):429-435, 1994.
60.R. F. Ker. The design of soft collagenous load-bearing tissues. The Journal of Experimental Biology 202(Pt 23):3315-3324, 1999.
61.J. Van Der Meulen, and P. A. Leistikow. Tendon healing. Clinics in Plastic Surgery 4(3):439-458, 1977.
62.J. Glowacki, and S. Mizuno. Collagen scaffolds for tissue engineering. Biopolymers 89(5):338-344, 2008.
63.Z. Feng, T. Matsumoto, and T. Nakamura. Measurements of the mechanical properties of contracted collagen gels populated with rat fibroblasts or cardiomyocytes. Journal of Artificial Organs 6(3):192-196, 2003.
64.E. Bell, B. Ivarsson, and C. Merrill. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proceedings of the National Academy of Sciences of the United States of America 76(3):1274-1278, 1979.
65.K. D. Costa, E. J. Lee, and J. W. Holmes. Creating alignment and anisotropy in engineered heart tissue: role of boundary conditions in a model three-dimensional culture system. Tissue Engineering 9(4):567-577, 2003.
66.H. P. Ehrlich, and J. B. Rajaratnam. Cell locomotion forces versus cell contraction forces for collagen lattice contraction: an in vitro model of wound contraction. Tissue & Cell 22(4):407-417, 1990.
67.M. Y. Chen, L. Jeng, Y. L. Sun, C. F. Zhao, M. E. Zobitz, S. L. Moran, P. C. Amadio, and K. N. An. Contraction of collagen gels seeded with tendon cells. Biorheology 43(3-4):337-345, 2006.
68.M. Y. Chen, Y. Sun, C. Zhao, M. E. Zobitz, K. N. An, S. L. Moran, and P. C. Amadio. Factors related to contraction and mechanical strength of collagen gels seeded with canine endotenon cells. Journal of Biomedical Materials Research Part B: Applied Biomaterials 82(2):519-525, 2007.
69.S. Wakitani, T. Goto, S. J. Pineda, R. G. Young, J. M. Mansour, A. I. Caplan, and V. M. Goldberg. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. Journal of Bone and Joint Surgery - American Volume 76(4):579-592, 1994.
70.R. G. Young, D. L. Butler, W. Weber, A. I. Caplan, S. L. Gordon, and D. J. Fink. Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. Journal of Orthopaedic Research 16(4):406-413, 1998.
71.H. A. Awad, D. L. Butler, G. P. Boivin, F. N. Smith, P. Malaviya, B. Huibregtse, and A. I. Caplan. Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Engineering 5(3):267-277, 1999.
72.N. Juncosa-Melvin, G. P. Boivin, M. T. Galloway, C. Gooch, J. R. West, A. M. Sklenka, and D. L. Butler. Effects of cell-to-collagen ratio in mesenchymal stem cell-seeded implants on tendon repair biomechanics and histology. Tissue Engineering 11(3-4):448-457, 2005.
73.V. S. Nirmalanandhan, M. S. Levy, A. J. Huth, and D. L. Butler. Effects of cell seeding density and collagen concentration on contraction kinetics of mesenchymal stem cell-seeded collagen constructs. Tissue Engineering 12(7):1865-1872, 2006.
74.C. L. Huang, C. W. Chang, J. D. Liao, Y. T. Wu, M. S. Ju, and C. C. K. Lin. Cells anchored upon a thin organic film with different nano-mechanical properties. Applied Surface Science 255(2):301-303, 2008.
75.Y. T. Yang, J. D. Liao, Y. L. Lee, C. W. Chang, and H. J. Tsai. Ultra-thin phospholipid layers physically adsorbed upon glass characterized by nano-indentation at the surface contact level. Nanotechnology 20(19), 2009.
76.J. C. Love, L. A. Estroff, J. K. Kriebel, R. G. Nuzzo, and G. M. Whitesides. Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chemical Reviews 105(4):1103-1169, 2005.
77.Y. Lin, X. Chen, Z. Yan, L. Liu, W. Tang, X. Zheng, Z. Li, J. Qiao, S. Li, and W. Tian. Multilineage differentiation of adipose-derived stromal cells from GFP transgenic mice. Molecular and Cellular Biochemistry 285(1-2):69-78, 2006.
78.H. Omae, C. Zhao, Y. L. Sun, K. N. An, and P. C. Amadio. Multilayer tendon slices seeded with bone marrow stromal cells: a novel composite for tendon engineering. Journal of Orthopaedic Research 27(7):937-942, 2009.
79.C. C. Berry, J. C. Shelton, D. L. Bader, and D. A. Lee. Influence of external uniaxial cyclic strain on oriented fibroblast-seeded collagen gels. Tissue Engineering 9(4):613-624, 2003.
80.C. Cacou, D. Palmer, D. A. Lee, D. L. Bader, and J. C. Shelton. A system for monitoring the response of uniaxial strain on cell seeded collagen gels. Medical Engineering & Physics 22(5):327-333, 2000.
81.Y. Shi, and I. Vesely. Fabrication of mitral valve chordae by directed collagen gel shrinkage. Tissue Engineering 9(6):1233-1242, 2003.
82.Y. C. Fung. Elasticity of soft tissues in simple elongation. American Journal of Physiology 213(6):1532-1544, 1967.
83.A. J. Keung, S. Kumar, and D. V. Schaffer. Presentation counts: microenvironmental regulation of stem cells by biophysical and material cues. Annual Review of Cell and Developmental Biology 26:533-556, 2010.
84.D. E. Discher, P. Janmey, and Y. L. Wang. Tissue cells feel and respond to the stiffness of their substrate. Science 310(5751):1139-1143, 2005.
85.K. A. Kilian, B. Bugarija, B. T. Lahn, and M. Mrksich. Geometric cues for directing the differentiation of mesenchymal stem cells. Proceedings of the National Academy of Sciences of the United States of America 107(11):4872-4877, 2010.
86.M. J. Dalby, N. Gadegaard, R. Tare, A. Andar, M. O. Riehle, P. Herzyk, C. D. Wilkinson, and R. O. Oreffo. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nature Materials 6(12):997-1003, 2007.
87.Z. Lu, B. Z. Doulabi, C. Huang, R. A. Bank, and M. N. Helder. Collagen type II enhances chondrogenesis in adipose tissue-derived stem cells by affecting cell shape. Tissue Engineering Part A 16(1):81-90, 2010.
88.J. M. Gimble, A. J. Katz, and B. A. Bunnell. Adipose-derived stem cells for regenerative medicine. Circulation Research 100(9):1249-1260, 2007.
89.S. Inoue, M. Imamura, A. Umezawa, and Y. Tabata. Attachment, proliferation and adipogenic differentiation of adipo-stromal cells on self-assembled monolayers of different chemical compositions. Journal of Biomaterials Science, Polymer Edition 19(7):893-914, 2008.
90.B. G. Keselowsky, D. M. Collard, and A. J. Garcia. Surface chemistry modulates fibronectin conformation and directs integrin binding and specificity to control cell adhesion. Journal of Biomedical Materials Research Part A 66(2):247-259, 2003.
91.M. H. Lee, D. A. Brass, R. Morris, R. J. Composto, and P. Ducheyne. The effect of non-specific interactions on cellular adhesion using model surfaces. Biomaterials 26(14):1721-1730, 2005.
92.Y. Arima, and H. Iwata. Effects of surface functional groups on protein adsorption and subsequent cell adhesion using self-assembled monolayers. Journal of Materials Chemistry 17(38):4079-4087, 2007.
93.H. Wang, S. Chen, L. Li, and S. Jiang. Improved method for the preparation of carboxylic acid and amine terminated self-assembled monolayers of alkanethiolates. Langmuir 21(7):2633-2636, 2005.
94.S. M. Mendoza, I. Arfaoui, S. Zanarini, F. Paolucci, and P. Rudolf. Improvements in the characterization of the crystalline structure of acid-terminated alkanethiol self-assembled monolayers on Au(111). Langmuir 23(2):582-588, 2007.
95.D. G. Castner, K. Hinds, and D. W. Grainger. X-ray photoelectron spectroscopy sulfur 2p study of organic thiol and disulfide binding interactions with gold surfaces. Langmuir 12(21):5083-5086, 1996.
96.J. Singh, and J. E. Whitten. Forces between polymer surfaces and self-assembled monolayers. Journal of Macromolecular Science, Part A: Pure and Applied Chemistry 45(11):885-892, 2008.
97.O. Dannenberger, K. Weiss, H. J. Himmel, B. Jager, M. Buck, and C. Woll. An orientation analysis of differently endgroup-functionalised alkanethiols adsorbed on Au substrates. Thin Solid Films 307(1-2):183-191, 1997.
98.R. Arnold, W. Azzam, A. Terfort, and C. Woll. Preparation, modification, and crystallinity of aliphatic and aromatic carboxylic acid terminated self-assembled monolayers. Langmuir 18(10):3980-3992, 2002.
99.P. Fenter, P. Eisenberger, and K. S. Liang. Chain-length dependence of the structures and phases of CH3(CH2)n-1 SH self-assembled on Au(111). Physical Review Letters 70(16):2447-2450, 1993.
100.K. P. Fears, S. E. Creager, and R. A. Latour. Determination of the surface pK of carboxylic- and amine-terminated alkanethiols using surface plasmon resonance spectroscopy. Langmuir 24(3):837-843, 2008.
101.K. P. Fears, and R. A. Latour. Assessing the influence of adsorbed-state conformation on the bioactivity of adsorbed enzyme layers. Langmuir 25(24):13926-13933, 2009.
102.S. M. Mendoza, I. Arfaoui, S. Zanarini, F. Paolucci, and P. Rudolf. Improvements in the characterization of the crystalline structure of acid-terminated alkanethiol self-assembled monolayers on Au(111). Langmuir 23(2):582-588, 2007.
103.K. E. Michael, V. N. Vernekar, B. G. Keselowsky, J. C. Meredith, R. A. Latour, and A. J. Garcia. Adsorption-induced conformational changes in fibronectin due to interactions with well-defined surface chemistries. Langmuir 19(19):8033-8040, 2003.
104.T. Yeung, P. C. Georges, L. A. Flanagan, B. Marg, M. Ortiz, M. Funaki, N. Zahir, W. Ming, V. Weaver, and P. A. Janmey. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motility and the Cytoskeleton 60(1):24-34, 2005.
105.C. J. Wilson, R. E. Clegg, D. I. Leavesley, and M. J. Pearcy. Mediation of biomaterial-cell interactions by adsorbed proteins: a review. Tissue Engineering 11(1-2):1-18, 2005.
106.A. Huttenlocher, M. H. Ginsberg, and A. F. Horwitz. Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity. The Journal of Cell Biology 134(6):1551-1562, 1996.
107.S. P. Palecek, J. C. Loftus, M. H. Ginsberg, D. A. Lauffenburger, and A. F. Horwitz. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385(6616):537-540, 1997.
108.Z. Mostafavi-Pour, J. A. Askari, S. J. Parkinson, P. J. Parker, T. T. Ng, and M. J. Humphries. Integrin-specific signaling pathways controlling focal adhesion formation and cell migration. The Journal of Cell Biology 161(1):155-167, 2003.
109.P. Roach, D. Eglin, K. Rohde, and C. C. Perry. Modern biomaterials: a review - bulk properties and implications of surface modifications. Journal of Materials Science: Materials in Medicine 18(7):1263-1277, 2007.
110.C. C. Barrias, M. C. Martins, G. Almeida-Porada, M. A. Barbosa, and P. L. Granja. The correlation between the adsorption of adhesive proteins and cell behaviour on hydroxyl-methyl mixed self-assembled monolayers. Biomaterials 30(3):307-316, 2009.
111.M. T. Bernards, and S. Jiang. pH-induced conformation changes of adsorbed vitronectin maximize its bovine aortic endothelial cell binding ability. Journal of Biomedical Materials Research, Part A 87(2):505-514, 2008.
112.S. F. Chen, L. Y. Liu, J. Zhou, and S. Y. Jiang. Controlling antibody orientation on charged self-assembled monolayers. Langmuir 19(7):2859-2864, 2003.
113.B. G. Keselowsky, D. M. Collard, and A. J. Garcia. Surface chemistry modulates fibronectin conformation and directs integrin binding and specificity to control cell adhesion. Journal of Biomedical Materials Research, Part A 66(2):247-259, 2003.
114.L. Vroman, and A. L. Adams. IDENTIFICATION OF RAPID CHANGES AT PLASMA SOLID INTERFACES. Journal of Biomedical Materials Research (1):43-67, 1969.
115.D. J. Fabrizius-Homan, and S. L. Cooper. A comparison of the adsorption of three adhesive proteins to biomaterial surfaces. Journal of Biomaterials Science, Polymer Edition 3(1):27-47, 1991.
116.Z. Lu, B. Z. Doulabi, C. Huang, R. A. Bank, and M. N. Helder. Collagen type II enhances chondrogenesis in adipose tissue-derived stem cells by affecting cell shape. Tissue Engineering, Part A 16(1):81-90, 2010.
117.A. Woods, G. Wang, and F. Beier. Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactions. Journal of Cellular Physiology 213(1):1-8, 2007.
118.P. Friedl. Prespecification and plasticity: shifting mechanisms of cell migration. Current Opinion in Cell Biology 16(1):14-23, 2004.
119.P. Friedl, and K. Wolf. Plasticity of cell migration: a multiscale tuning model. The Journal of Cell Biology 188(1):11-19, 2009.
120.X. Zhang, G. Jiang, Y. Cai, S. J. Monkley, D. R. Critchley, and M. P. Sheetz. Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nature Cell Biology, 2008.
121.R. J. Eddy, L. M. Pierini, F. Matsumura, and F. R. Maxfield. Ca2+-dependent myosin II activation is required for uropod retraction during neutrophil migration. Journal of Cell Science 113 ( Pt 7):1287-1298, 2000.
122.N. A. Morin, P. W. Oakes, Y. M. Hyun, D. Lee, Y. E. Chin, M. R. King, T. A. Springer, M. Shimaoka, J. X. Tang, J. S. Reichner, and M. Kim. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. The Journal of Experimental Medicine 205(1):195-205, 2008.
123.J. Jacobelli, F. C. Bennett, P. Pandurangi, A. J. Tooley, and M. F. Krummel. Myosin-IIA and ICAM-1 regulate the interchange between two distinct modes of T cell migration. The Journal of Immunology 182(4):2041-2050, 2009.
124.B. Z. Katz, E. Zamir, A. Bershadsky, Z. Kam, K. M. Yamada, and B. Geiger. Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Molecular Biology of the Cell 11(3):1047-1060, 2000.
125.R. M. Salasznyk, W. A. Williams, A. Boskey, A. Batorsky, and G. E. Plopper. Adhesion to Vitronectin and Collagen I Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells. Journal of Biomedicine and Biotechnology 2004(1):24-34, 2004.
126.R. McBeath, D. M. Pirone, C. M. Nelson, K. Bhadriraju, and C. S. Chen. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Developmental Cell 6(4):483-495, 2004.
127.C. Guidry, and F. Grinnell. Studies on the mechanism of hydrated collagen gel reorganization by human skin fibroblasts. Journal of Cell Science 79:67-81, 1985.
128.Z. Feng, M. Ishibashi, Y. Nomura, T. Kitajima, and T. Nakamura. Constraint stress, microstructural characteristics, and enhanced mechanical properties of a special fibroblast-embedded collagen construct. Artificial Organs 30(11):870-877, 2006.
129.V. H. Barocas, and R. T. Tranquillo. An anisotropic biphasic theory of tissue-equivalent mechanics: The interplay among cell traction, fibrillar network deformation, fibril alignment, and cell contact guidance. Journal of Biomechanical Engineering-Transactions of the Asme 119(2):137-145, 1997.
130.N. L'Heureux, L. Germain, R. Labbe, and F. A. Auger. In vitro construction of a human blood vessel from cultured vascular cells: a morphologic study. Journal of Vascular Surgery 17(3):499-509, 1993.
131.M. Eastwood, R. Porter, U. Khan, G. McGrouther, and R. Brown. Quantitative analysis of collagen gel contractile forces generated by dermal fibroblasts and the relationship to cell morphology. Journal of Cellular Physiology 166(1):33-42, 1996.
132.J. F. Chapuis, and P. Agache. A new technique to study the mechanical properties of collagen lattices. Journal of Biomechanics 25(1):115-120, 1992.
133.J. H. Wang. Mechanobiology of tendon. Journal of Biomechanics 39(9):1563-1582, 2006.
134.D. Seliktar, R. A. Black, R. P. Vito, and R. M. Nerem. Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodeling in vitro. Annals of Biomedical Engineering 28(4):351-362, 2000.
135.K. Chokalingam, N. Juncosa-Melvin, S. A. Hunter, C. Gooch, C. Frede, J. Florert, G. Bradica, R. Wenstrup, and D. L. Butler. Tensile stimulation of murine stem cell-collagen sponge constructs increases collagen type I gene expression and linear stiffness. Tissue Engineering Part A 15(9):2561-2570, 2009.
136.R. K. Harrison, M. E. Jones, E. Clayton, A. O. Grobbelaar, and R. Sanders. Mapping of vascular endothelium in the human flexor digitorum profundus tendon. Journal of Hand Surgery (American Volume) 28(5):806-813, 2003.
137.P. R. Manske, R. H. Gelberman, J. S. Vande Berg, and P. A. Lesker. Intrinsic flexor-tendon repair. A morphological study in vitro. Journal of Bone and Joint Surgery - American Volume 66(3):385-396, 1984.
138.A. J. Banes, K. Donlon, G. W. Link, Y. Gillespie, A. G. Bevin, H. D. Peterson, D. Bynum, S. Watts, and L. Dahners. Cell populations of tendon: a simplified method for isolation of synovial cells and internal fibroblasts: confirmation of origin and biologic properties. Journal of Orthopaedic Research 6(1):83-94, 1988.
139.A. L. Bertone, T. S. Stashak, F. W. Smith, and R. W. Norrdin. A comparison of repair methods for gap healing in equine flexor tendon. Veterinary Surgery 19(4):254-265, 1990.
140.H. Jann, M. Blaik, R. Emerson, M. Tomioka, L. Stein, and D. Moll. Healing characteristics of deep digital flexor tenorrhaphy within the digital sheath of horses. Veterinary Surgery 32(5):421-430, 2003.
141.M. J. Silva, M. I. Boyer, and R. H. Gelberman. Recent progress in flexor tendon healing. Journal of Orthopaedic Science 7(4):508-514, 2002.
142.K. L. Silfverskiold, E. J. May, and A. H. Tornvall. Gap formation during controlled motion after flexor tendon repair in zone II: a prospective clinical study. Journal of Hand Surgery (American Volume) 17(3):539-546, 1992.
143.N. Juncosa-Melvin, J. T. Shearn, G. P. Boivin, C. Gooch, M. T. Galloway, J. R. West, V. S. Nirmalanandhan, G. Bradica, and D. L. Butler. Effects of mechanical stimulation on the biomechanics and histology of stem cell-collagen sponge constructs for rabbit patellar tendon repair. Tissue Engineering 12(8):2291-2300, 2006.
144.A. Crovace, L. Lacitignola, E. Francioso, and G. Rossi. Histology and immunohistochemistry study of ovine tendon grafted with cBMSCs and BMMNCs after collagenase-induced tendinitis. Veterinary and Comparative Orthopaedics and Traumatology 21(4):329-336, 2008.
145.R. K. Smith. Mesenchymal stem cell therapy for equine tendinopathy. Disability and Rehabilitation 30(20-22):1752-1758, 2008.
146.J. L. Kelsey. Upper extremity disorders: frequency, impact, and cost. New York, Churchill Livingstone, 1997.
147.H. E. Kleinert, S. Schepel, and T. Gill. Flexor tendon injuries. Surgical Clinics of North America 61(2):267-286, 1981.
148.J. W. Strickland. Development of flexor tendon surgery: twenty-five years of progress. Journal of Hand Surgery - American Volume. 25(2):214-235, 2000.
149.J. O. Small, M. D. Brennen, and J. Colville. Early active mobilisation following flexor tendon repair in zone 2 [see comments]. Journal of Hand Surgery - British Volume 14(4):383-391, 1989.
150.S. B. Harris, D. Harris, A. J. Foster, and D. Elliot. The aetiology of acute rupture of flexor tendon repairs in zones 1 and 2 of the fingers during early mobilization. J Hand Surg [Br] 24(3):275-280, 1999.
151.P. R. Manske. Flexor tendon healing. J Hand Surg 13B(3):237-245, 1988.
152.D. P. Mass, and R. J. Tuel. Intrinsic healing of the laceration site in human superficialis flexor tendons in vitro. Journal of Hand Surgery - American Volume 16(1):24-30, 1991.
153.M. I. Boyer, C. A. Goldfarb, and R. H. Gelberman. Recent progress in flexor tendon healing. The modulation of tendon healing with rehabilitation variables. Journal of Hand Therapy 18(2):80-85; quiz 86, 2005.
154.M. E. Jones, V. Mudera, R. A. Brown, A. D. Cambrey, A. O. Grobbelaar, and D. A. McGrouther. The early surface cell response to flexor tendon injury. Journal of Hand Surgery - American Volume 28(2):221-230, 2003.
155.R. H. Gelberman, J. S. Vande Berg, G. N. Lundborg, and W. H. Akeson. Flexor tendon healing and restoration of the gliding surface. An ultrastructural study in dogs. Journal of Bone & Joint Surgery - American Volume 65(1):70-80, 1983.
156.S. Tozer, and D. Duprez. Tendon and ligament: development, repair and disease. Birth Defects Research Part C, Embryo Today: Reviews 75(3):226-236, 2005.
157.K. W. Liechty, T. C. MacKenzie, A. F. Shaaban, A. Radu, A. M. Moseley, R. Deans, D. R. Marshak, and A. W. Flake. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nature Medicine 6(11):1282-1286, 2000.
158.D. J. Prockop, I. Sekiya, and D. C. Colter. Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy 3(5):393-396, 2001.
159.H. A. Awad, G. P. Boivin, M. R. Dressler, F. N. L. Smith, R. G. Young, and D. L. Butler. Repair of patellar tendon injuries using a cell-collagen composite. Journal of Orthopaedic Research 21(3):420-431, 2003.
160.G. S. Kryger, A. K. Chong, M. Costa, H. Pham, S. J. Bates, and J. Chang. A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. Journal of Hand Surgery - American Volume 32(5):597-605, 2007.
161.M. Mian, R. Aloisi, D. Benetti, S. Rosini, and R. Fantozzi. Potential role of heterologous collagen in promoting cutaneous wound repair in rats. International journal of tissue reactions 14 Suppl:43-52, 1992.
162.H. Ishikawa, T. Koshino, R. Takeuchi, and T. Saito. Effects of collagen gel mixed with hydroxyapatite powder on interface between newly formed bone and grafted achilles tendon in rabbit femoral bone tunnel. Biomaterials 22(12):1689-1694, 2001.



連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top