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研究生:張峻瑋
研究生(外文):Chun-Wei Chang
論文名稱:功能性韌帶組織工程最佳化:化學環境
論文名稱(外文):Chemical Optimization for Functional Ligament Tissue Engineering
指導教授:趙本秀
指導教授(外文):Pen-Hsiu Chao
口試委員:蔡偉博葉伊純
口試委員(外文):Wei-Bor TsaiYi-Cheun Yeh
口試日期:2018-09-10
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2018
畢業學年度:107
語文別:英文
論文頁數:36
中文關鍵詞:前十字韌帶細胞膠原蛋白纖維母細胞生長因子2型轉化生長因子-β1血纖維蛋白
DOI:10.6342/NTU201804124
相關次數:
  • 被引用被引用:0
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前十字韌帶受限於自身組織修復能力,因此組織工程也許可能提供足量新生組織。高分子緻密纖維材料雖具有良好力學強度,卻會限制細胞遷移以及胞外基質(ECM)沉積。本研究發現在緻密纖維材料上給予膠原蛋白塗層能幫助前十字韌帶細胞遷移進而讓細胞平均分散在整體材料中。我們篩選不同生長激素後發現纖維母細胞生長因子2型(FGF-2)能增加細胞數量,轉化生長因子-β1(TGF-β1) 能增加膠原蛋白生成,且次序性給予兩種不同生長激素比起單獨或混合給予能提高細胞數以及膠原蛋白的生成。最後我們利用血纖維蛋白凝膠將兩塊材料製備成複合物,不僅提高機械強度更能增進新生膠原蛋白的累積。未來我們會更進一步探討血纖維蛋白凝膠對生長因子的交互作用。
The limited repair ability of anterior cruciate ligament (ACL) prompted research in ligament tissue engineering to be a promising treatment strategy. We aim to optimize current issues of poor infiltration, poor ECM deposition and limited construct size. Collagen coating improved cell infiltration and resulted in homogeneous ligament cellularity on the densely fibrous PLLA scaffold. We found that the sequential growth factor supplementation of fibroblast growth factor-2 (FGF-2) and transforming growth factor beta-1 (TGF-β1) increased ACL cellularity and collagen deposition. To increase construct size, we laminated two layers of scaffolds with fibrin, which further improved collagen deposition and mechanical properties. Future study will focus on the interaction between fibrin gel and growth factors.
中文摘要…………………………………………………………………………………………………………………………………iii
Abstract…………………………………………………………………………………………………………………………………iv
Chapter 1 Introduction………………………………………………………………………………………………1
Chapter 2 Materials and Methods………………………………………………………………………5
2.1 Electrospun Scaffold…………………………………………………………………5
2.2 ECM Coating………………………………………………………………………………………………………………5
2.3 Cell culture……………………………………………………………………………………………………………6
2.4 Laminated scaffold……………………………………………………………………………………………7
2.5 Imaging ………………………………………………………………………………………………………………………7
2.6 Biochemical contents assay………………………………………………………………………8
2.7 RNA extraction and quantification of gene expression level……………………………………………………………………………………………………………………………………………9
2.8 Mechanical test…………………………………………………………………………………………………11
2.9 Statistical Analysis..………………………………………………………………………………11
Chapter 3 Results…………………………………………………………………………………………………………12
3.1 ECM coated PLLA scaffold for cell infiltration………………12
3.2 Growth factor supplement screening for ACL in vitro culture……………………………………………………………………………………………………………………………………16
3.3 Sequential growth factor supplementation………………………………18
3.4 Scaffold lamination………………………………………………………………………………………23
Chapter 4 Discussion…………………………………………………………………………………………………28
References……………………………………………………………………………………………………………………………32
1.A. M. Kiapour, R.F.a.M.M.M., Basic science of anterior cruciate ligament injury and repair. Bone Joint Res, 2014. 3(2): p. 20-31.
2.Nguyen DT, D.S., Tak PP, Woo SL, Blankevoort L, van Dijk NC, Histological characteristics of ligament healing after bio-enhanced repair of the transected goat ACL. J Exp Orthop, 2015. 2(1): p. 4.
3.Domnick C, R.M., Herbort M, Biomechanics of the anterior cruciate ligament: Physiology, rupture and reconstruction techniques. World J Orthop, 2016. 7(2): p. 82-93.
4.Chen J, X.J., Wang A, Zheng M., Scaffolds for tendon and ligament repair: review of the efficacy of commercial products. Expert Rev Med Devices, 2009. 6(1): p. 61-73.
5.Megan A. Walters, M.C.C., Rabindra Karki, Eddie Knox, Gary Levengood, Saadiq F. El-Amin, Anterior Cruciate Ligament Tissue Engineering: A Review of Current Investigations. Journal of Nanotechnology and Materials Science, 2016. 3(1): p. 3-9.
6.Yates EW, R.A., Foley GT, Khan WS, Cartmell S, Anand SJ., Ligament tissue engineering and its potential role in anterior cruciate ligament reconstruction. Stem Cells Int., 2012. 2012: p. 1-6.
7.Laurent CP, D.D., Mainard D, Ganghoffer JF, Rahouadj R., A multilayer braided scaffold for Anterior Cruciate Ligament: mechanical modeling at the fiber scale. J Mech Behav Biomed Mater., 2012. 12: p. 184-96.
8.Teuschl A, H.P., Nürnberger S, van Griensven M, Redl H, Nau T., A Novel Silk Fiber-Based Scaffold for Regeneration of the Anterior Cruciate Ligament: Histological Results From a Study in Sheep. Am J Sports Med., 2016. 44(6): p. 1547-57.
9.A., B., Proline precursors to sustain Mammalian collagen synthesis. J Nutr., 2008. 138(10): p. 2021-2024.
10.Lee CH, S.H., Cho IH, Kang YM, Kim IA, Park KD, Shin JW, Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast. Biomaterials, 2005. 26(11): p. 1261-70.
11.Lu HH, C.J.J., Manuel S, Freeman JW, Attawia MA, Ko FK, Laurencin CT., Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies. Biomaterials., 2005. 26(23): p. 4805-16.
12.Grace Chao PH, H.H., Tseng HY., Electrospun microcrimped fibers with nonlinear mechanical properties enhance ligament fibroblast phenotype. Biofabrication., 2014. 6(3): p. 035008.
13.Bogdanowicz DR, L.H., Designing the stem cell microenvironment for guided connective tissue regeneration. Ann N Y Acad Sci., 2017. 1410(1): p. 3-25.
14.Leong MF, R.M., Lim TC, Chian KS., In vitro cell infiltration and in vivo cell infiltration and vascularization in a fibrous, highly porous poly(D,L-lactide) scaffold fabricated by cryogenic electrospinning technique. J Biomed Mater Res A, 2009. 91(1): p. 231-40.
15.Baker BM, G.A., Metter RB, Nathan AS, Marklein RA, Burdick JA, Mauck RL, The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials, 2008. 29(15): p. 2348-58.
16.Szentivanyi A, C.T., Zernetsch H, Glasmacher B., Electrospun cellular microenvironments: Understanding controlled release and scaffold structure. Adv Drug Deliv Rev., 2011. 63(4-5): p. 209-20.
17.Zhong S, Z.Y., Lim CT., Fabrication of large pores in electrospun nanofibrous scaffolds for cellular infiltration: a review. Tissue Eng Part B Rev. , 2012. 18(2).
18.Carey SP, G.Z., Martin KE, Romero B, Williams RM, Reinhart-King CA., Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK. Integr Biol (Camb), 2016. 8(8): p. 821-35.
19.Andreas Herchenhan, F.U., Pernilla Eliasson, MaryAnn Weis,David Eyre, Karl E. Kadler, S. Peter Magnusson, and Michael Kjaer, Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells. J Biol Chem, 2015. 290(26): p. 16440-16450.
20.Molloy T, W.Y., Murrell G., The roles of growth factors in tendon and ligament healing. Sports Med., 2003. 33(5): p. 381-94.
21.Klein MB, Y.N., Pham H, Longaker MT, Chang J., Flexor tendon healing in vitro: effects of TGF-beta on tendon cell collagen production. J Hand Surg Am., 2002. 27(4): p. 615-20.
22.Petrov VV, F.R., Lijnen PJ., Stimulation of collagen production by transforming growth factor-beta1 during differentiation of cardiac fibroblasts to myofibroblasts. Hypertension., 2002. 39(2): p. 258-63.
23.Rickert M, J.M., Adiyaman M, Richter W, Simank HG., A growth and differentiation factor-5 (GDF-5)-coated suture stimulates tendon healing in an Achilles tendon model in rats. Growth Factors., 2001. 19(2): p. 115-26.
24.Nerurkar NL, B.B., Sen S, Wible EE, Elliott DM, Mauck RL, Nanofibrous biologic laminates replicate the form and function of the annulus fibrosus. Nat Mater., 2009. 8(12): p. 986-92.
25.Qin TW, C.Q., Sun YL, Steinmann SP, Amadio PC, An KN, Zhao C., Mechanical characteristics of native tendon slices for tissue engineering scaffold. J Biomed Mater Res B Appl Biomater., 2012. 100(3): p. 752-8.
26.Mikos AG, S.G., Leite SM, Vacanti JP, Langer R., Laminated three-dimensional biodegradable foams for use in tissue engineering. Biomaterials., 1993. 14(5): p. 323-30.
27.Sánchez M, A.E., Azofra J, Andía I, Padilla S, Mujika I., Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med, 2007. 35(2): p. 245-51.
28.Anitua E, S.M., Nurden AT, Nurden P, Orive G, Andía I., New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol., 2006. 24(5): p. 227-34.
29.Breidenbach AP, D.N., Lu Y, Rao M, Shearn JT, Rowe DW, Kadler KE, Butler DL., Fibrin gels exhibit improved biological, structural, and mechanical properties compared with collagen gels in cell-based tendon tissue-engineered constructs. Tissue Eng Part A., 2015. 21(3-4): p. 438-50.
30.Plant AL, B.K., Spurlin TA, Elliott JT., Cell response to matrix mechanics: Focus on collagen. Biochim Biophys Acta., 2009. 1793(893-902).
31.Parameswaran K1, R.K., Zuo J, Janssen LJ, O''Byrne PM, Cox PG., Extracellular matrix regulates human airway smooth muscle cell migration. Eur Respir J., 2004. 24(4): p. 545-51.
32.Whitley CB, R.M., Draper KA, Dutton CM, Neglia JP., Diagnostic test for mucopolysaccharidosis. I. Direct method for quantifying excessive urinary glycosaminoglycan excretion. Clin Chem., 1989. 35(3): p. 374-9.
33.Stegemann H, S.K., Determination of hydroxyproline. Clin Chim Acta., 1967. 18(2): p. 267-73.
34.Livak KJ, S.T., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods., 2001. 25(4): p. 402-8.
35.Hubbard B, B.-T.J., Nugent MA, Smith ML, Fibronectin Fiber Extension Decreases Cell Spreading and Migration. J Cell Physiol., 2016. 231(8): p. 1728-36.
36.Greenberg JH, S.S., Seppä H, Tyl Hewitt A., Role of collagen and fibronectin in neural crest cell adhesion and migration. Dev Biol., 1981. 87(2): p. 259-66.
37.Brent AE1, T.C., FGF acts directly on the somitic tendon progenitors through the Ets transcription factors Pea3 and Erm to regulate scleraxis expression. Development., 2004. 131(16): p. 3885-96.
38.Hankemeier S, K.M., Zeichen J, Jagodzinski M, Barkhausen T, Bosch U, Krettek C, Van Griensven M., Modulation of proliferation and differentiation of human bone marrow stromal cells by fibroblast growth factor 2: potential implications for tissue engineering of tendons and ligaments. Tissue Eng., 2005. 11(1-2): p. 41-9.
39.Takayama S, M.S., Miki Y, Ikezawa K, Tasaka S, Terashima A, Asano T, Okada H., Effects of basic fibroblast growth factor on human periodontal ligament cells. J Periodontal Res., 1997. 32(8): p. 667-75.
40.Silverio-Ruiz KG, M.A., Garlet GP, Barbosa CF, Silva JS, Cicarelli RM, Valentini SR, Abi-Rached RS, Junior CR., Opposite effects of bFGF and TGF-beta on collagen metabolism by human periodontal ligament fibroblasts. Cytokine., 2007. 39(2): p. 130-7.
41.Hyun SY, L.J., Kang KJ, Jang YJ., Effect of FGF-2, TGF-β-1, and BMPs on Teno/Ligamentogenesis and Osteo/Cementogenesis of Human Periodontal Ligament Stem Cells. Mol Cells., 2017. 40(8): p. 550-557.
42.Fafeur V, T.B., Blum J, Böhlen P., Basic FGF treatment of endothelial cells down-regulates the 85-KDa TGF beta receptor subtype and decreases the growth inhibitory response to TGF-beta 1. Growth Factors., 1990. 3(3): p. 237-45.
43.Lapiere CM, N.B., Pierard GE., Interaction between collagen type I and type III in conditioning bundles organization. Connect Tissue Res., 1977. 5(1): p. 21-9.
44.Liu SH, Y.R., al-Shaikh R, Lane JM., Collagen in tendon, ligament, and bone healing. A current review. Clin Orthop Relat Res., 1995. 318: p. 265-78.
45.Ito Y, T.N., Yoshitaka T, Ueno-Kudoh H, Sato T, Yokoyama S, Nishida K, Akimoto T, Takahashi M, Miyaki S, Asahara H, The Mohawk homeobox gene is a critical regulator of tendon differentiation. Proc Natl Acad Sci U S A., 2010. 107(23): p. 10538-42.
46.Nakahara H, H.A., Otabe K, Ayabe F, Matsukawa T, Onizuka N, Ito Y, Ozaki T, Lotz MK, Asahara H., Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation. Arthritis Rheum. , 2013. 65(8): p. 2081-9.
47.Baek J, S.S., Choi W, Jin S, Grogan SP, D''Lima DD., Meniscal Tissue Engineering Using Aligned Collagen Fibrous Scaffolds: Comparison of Different Human Cell Sources. Tissue Eng Part A., 2018. 24(1-2): p. 81-93.
48.Spicer PP, M.A., Fibrin glue as a drug delivery system. J Control Release., 2010. 148(1): p. 49-55.
49.Jiao Y, P.X., Zhai G., Advances in Hyaluronic Acid-Based Drug Delivery Systems. Curr Drug Targets., 2016. 17(6): p. 720-30.
50.Huang Q, G.J., Hutmacher DW, Lee EH., In vivo mesenchymal cell recruitment by a scaffold loaded with transforming growth factor beta1 and the potential for in situ chondrogenesis. Tissue Eng. , 2002. 8(3): p. 469-82.
51.Jeon O, R.S., Chung JH, Kim BS., Control of basic fibroblast growth factor release from fibrin gel with heparin and concentrations of fibrinogen and thrombin. J Control Release., 2005. 105(3): p. 249-59.
52.Jing Xie, J.J., Yanjun Zhang, ChunMing Xu, Lin Yin, Chunli Wang, Peter C. Y. Chen, and K. L. Paul Sung, Up-regulation expressions of lysyl oxidase family in Anterior Cruciate Ligament and Medial Collateral Ligament fibroblasts induced by Transforming Growth Factor-Beta 1. Int Orthop., 2012. 36(1): p. 207-213.
53.Xie J, W.C., Huang DY, Zhang Y, Xu J, Kolesnikov SS, Sung KL, Zhao H., TGF-beta1 induces the different expressions of lysyl oxidases and matrix metalloproteinases in anterior cruciate ligament and medial collateral ligament fibroblasts after mechanical injury. J Biomech., 2013. 46(5): p. 890-8.
54.Guang Yang, B.B.R., and Rocky S. Tuan, Tendon and Ligament Regeneration and Repair: Clinical Relevance and Developmental Paradigm. Birth Defects Res C Embryo Today, 2013. 99(3): p. 203-222.
55.Howard PS, K.U., Taliwal R, Korostoff JM., Mechanical forces alter extracellular matrix synthesis by human periodontal ligament fibroblasts. J Periodontal Res., 1998. 33(8): p. 500-8.
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