Please use this identifier to cite or link to this item:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/38193Full metadata record
| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 林峰輝 | |
| dc.contributor.author | Pei-Ru Chen | en |
| dc.contributor.author | 陳姵如 | zh_TW |
| dc.date.accessioned | 2021-06-13T16:27:45Z | - |
| dc.date.available | 2005-07-22 | |
| dc.date.copyright | 2005-07-22 | |
| dc.date.issued | 2005 | |
| dc.date.submitted | 2005-07-14 | |
| dc.identifier.citation | [1] 王錫崗, 麥麗敏. 簡明解剖生理學. 三版, 匯華圖書出版有限公司.
[2] Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube. Plast Reconstr Surg 1990;85(3):419–424. [3] Peter J. Evans, Susan E. Mackinnon, Allan D.O. Levi, Judith A. Wade, Daniel A. Hunter, Yasushi Nakao, Rajiv Midha. Cold preserved nerve allografts: changes in basement membrane, viability, immunogenicity, and regeneration. Muscle and Nerve 1998;21(11):1507–1522. [4] Fawcett JW, Keynes RJ. Peripheral nerve regeneration. Ann Rev Neurosci 1990;13:43-60. [5] Fields RD, Le Beau JM, Longo FM, Ellisman MH. Nerve regeneration through artificial tubular implants. Prog Neurobiol 1989;33:87-134. [6] Nicoli Aldini N, Perego G, Cella GD, Maltarello MC, Fini M, Rocca M, Giardino R. Effectiveness of a bioabsorbable conduit in the repair of peripheral nerves. Biomaterials. 1996;17(10):959-62. [7] Den Dunnen WFA, Schakenraad GJ, Zondervan AJ, Pennings B, Lei VD, Robinson PH. A new PLLA/PCL copolymer for nerve regeneration. J Mater Sci Mater Med 1993;4:521-525. [8] Robinson PH, van der Lei B, Hoppen HJ, Leenslag JW, Pennings AJ, Nieuwenhuis P. Nerve regeneration through a two-ply biodegradable nerve guide in the rat and the influence of ACTH4-9 nerve growth factor. Microsurgery 1991;12(6):412-9. [9] Tountas CP, Bergman RA, Lewis TW, Stone HE, Pyrek JD, Mendenhall HV. A comparison of peripheral nerve repair using an absorbable tubulization device and conventional suture in primates. J Appl Biomater. 1993;4(3):261-8. [10] Michel Merle, A. Lee Dellon, James N. Campbell, Peter S. Chang. Complications from silicon-polymer intubulation of nerves. Microsurgery 1989;10(2):130–133. [11] Madison R, da Silva CF, Dikkes P, Chiu TH, Sidman RL. Increased rate of peripheral nerve regeneration using bioresorbable nerve guides and a laminin-containing gel. Exp Neurol 1985;88(3):767-72. [12] Evans GR, Brandt K, Widmer MS, Lu L, Meszlenyi RK, Gupta PK, Mikos AG, Hodges J, Williams J, Gurlek A, Nabawi A, Lohman R, Patrick CW Jr. In vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration. Biomaterials 1999;20(12):1109-15. [13] Agrawal CM, Athanasiou KA. Technique to control pH in vicinity of biodegrading PLA-PGA implants. J Biomed Mater Res 1997;38(2):105-14. [14] Suganuma J, Alexander H. Biological response of intramedullary bone to poly-L-lactic acid. J Appl Biomater 1993;4:13-27. [15] Itoh S, Takakuda K, Kawabata S, Aso Y, Kasai K, Itoh H, Shinomiya K. Evaluation of cross-linking procedures of collagen tubes used in peripheral nerve repair. Biomaterials 2002;23(23):4475-81. [16] Peppas NA, Ratner B, editor. In biomaterials science. New York: Academic Press 1996. p.63. [17] Bigi A, Cojazzi G, Panzavolta S, Rubini K, Roveri N. Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking. Biomaterials 2001;22:763-768. [18] Rich KM, Alexander TD, Pryor JC, Hollowell JP. Nerve growth factor enhances regeneration through silicone chambers. Exp Neurol 1989;105(2):162-70. [19] He C, Chen Z, Chen Z. Enhancement of motor nerve regeneration by nerve growth factor. Microsurgery 1992;13(3):151-4. [20] Whitworth IH, Brown RA, Dore CJ, Anand P, Green CJ, Terenghi G. Nerve growth factor enhances nerve regeneration through fibronectin grafts. J Hand Surg 1996;21(4):514-22. [21] Fine EG, Decosterd I, Papaloizos M, Zurn AD, Aebischer P. GDNF and NGF released by synthetic guidance channels support sciatic nerve regeneration across a long gap. Eur J Neurosci 2002;15(4):589-601. [22] Hanthamrongwit M, Reid WH, Grant MH. Chondroitin-6-sulphate incorporated into collagen gels for the growth of human keratinocytes: the effect of cross-linking agents and diamines. Biomaterials 1996;17(8):775-80. [23] Laemmel E, Penhoat J, Warocquier-Clerout R, Sigot-Luizard MF. Heparin immobilized on proteins usable for arterial prosthesis coating: growth inhibition of smooth-muscle cells. J Biomed Mater Res 1998;39(3):446-52. [24] Guenard V, Kleitman N, Morrissey TK, Bunge RP, Aebischer P. Syngeneic Schwann cells derived from adult nerves seeded in semipermeable guidance channels enhance peripheral nerve regeneration. J Neurosci 1992;12(9):3310-20. [25] Keeley R, Sabelman E, Kadlcik P. Synthetic nerve graft containing collagen and syngeneic Schwann cells improves functional, electrophysiological and histological parameters of peripheral nerve regeneration. Restorative Neurology and Neuroscience 1993;5:353-66. [26] Levi AD, Guenard V, Aebischer P, Bunge RP. The functional characteristics of Schwann cells cultured from human peripheral nerve after transplantation into a ap within the rat sciatic nerve. J Neurosci 1994;14(3):1309-19. [27] Wang KK, Costas PD, Bryan DJ. Inside-out vein graft promotes improved nerve regeneration in rats. Microsurgery 1993;14:608-618. [28] Jamal Mohammad, Jay Shenaq, Eric Rabinovsky, Saleh Shenaq. Modulation of peripheral nerve regeneration: a tissue-engineering approach. The role of amnion tube nerve conduit across a 1 cm nerve gap. Plast Reconstr Surg 2000;105:660-666. [29] Mohammad J, Shenaq J, Rabinovsky E. Modulation of peripheral nerve regeneration: a tissue-engineering approach. The role of amnion tube nerve conduit across a 1-centimeter nerve gap. Plast Reconstr Surg 2000;105(2): 660-666. [30] Carole A. Heath, Gregory E. Rutkowski. The development of bioartificial nerve grafts for peripheral-nerve regeneration. Trends Biotechnol 1998;16(4):163-8. [31] Lundborg G, Dahlin LB, Danielsen NP, Gelberman RH, Longo EM, Powell MC, Varon S. Nerve regeneration in silicone chambers: Influence of gap length and distal stump contents. Exp Neurol 1982;76:361-375. [32] Madison R, Da Silva CF, Dikkes P, Chiu TH, Sidman RL. Increased rate of peripheral nerve regeneration using bioresorbable nerve guides and a laminin-containing gel. Exp Neurol 1985;88:767-772. [33] Aebischer P, Salessiotis AN, Winn SR. Basic fibroblast growth factor released from synthetic guidance channels facilitates peripheral nerve regeneration across long nerve gaps. J Neurosci Res 1989;23:282-289. [34] Terada N, Bjursten LM, Dohi D, Lundborg G. Bioartificial nerve grafts based on absorbable guiding filament structures--early observations. Scand J Plast Reconstr Surg Hand Surg 1997;31(1):1-6. [35] Valentini, RF, Aebischer, P., Winn, SR and Galletti, PM. Collagen and laminin containing gels impede peripheral nerve regeneration through semipermeable nerve guidance channels. Exp Neurol 1987;98:350-356. [36] Aebischer P, Guenard V, Winn SR, Kunz S, Sacken H, Galetti PM. Blind-ended semipermeable guidance channels support peripheral nerve regeneration in the absence of a distal nerve stump. Brain Res 1988;454:179-187. [37] Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube. Plast Reconstr Surg 1990;85:419-424. [38] Kiyotani T, Nakamura T, Shimizu Y, Endo K. Experimental study of nerve regeneration in a biodegradable tube made from collagen and polyglycolic acid. ASAIO J 1995;41:M657-M661. [39] Den Dunnen WFA, Stokroos I, Blaauw EH, Holwerda A, Pennings AJ, Robinson PH, Schakenraad JM. Light-microscopic and electron-microscopic evaluation of short-term nerve regeneration using a biodegradable poly(DL-lactide-ε-caprolactone) nerve guide. J Biomed Mater Res 1996;31:105-115. [40] Rosen JM, Padilla JA, Nguyen KD, Padilla MA, Sabelman EE, Pham HN. Artificial nerve graft using collagen as an extracellular matrix for nerve repair compared with sutured autograft in a rat model. Ann Plast Surg 1990;25:375-387. [41] Werrbach-Perez K, Perez-Polo JR. De novo synthesis of NGF subunits in S-180 mouse sarcoma cell line. Neurochem Res 1987;12(10):875-883. [42] Levi-Montalcini, R. The development of the acoustico-vestibular centers in the chick embryo in the absence of afferent root fiber and of descending fiber tracts. J Comp Neuro 1949;91:209-241. [43] Thomas L. Darling, Eric M. Shooter. Methods for preparation and assay of nerve growth factor; Cell Culture Methods for Molecular and Cellular Biology 1984 (Eds. David W. Barnes, David A. Sinbasku). 79-93, Alan R. Liss, Inc. New York. [44] Levi-Montalcini, R. Events in the developing nervous system. Prog Brain Res 1964;4:1-29. [45] Arthur J. Vander, James H. Sherman, Dorothy S. Luciano. Human physiology. 7th edition, McGraw-Hill, Inc. [46] Ide C, Tohyama K, Yokota R, Nitatori T, Onodera S. Schwann cell basal lamina and nerve regeneration. Brain Res 1983;288(12):61-75. [47] S Hoffman, DR Friedlander, CM Chuong, M Grumet and GM Edelman. Differential contributions of Ng-CAM and N-CAM to cell adhesion in different neural regions. The Journal of Cell Biology 1986;103:145-158. [48] Arthur C. Guyton, John E. Hall. Textbook of medical Physiology. 9th edition. W. B. Saunders Company, Philadephia, Pennsylvania. 1995 [49] Blumcke S, Niedorf HR. Electron microscope studies of Schwann cells during the Wallerian degeneration with special reference to the cytoplasmic filaments. Acta Neuropathol (Berl) 1966;6(1):46-60. [50] Perez VJ, Moore BW. Wallerian degeneration in rabbit tibial nerve: changes in amounts of the S-100 protein. J Neurochem 1968;15(9):971-7. [51] A. Bigi, S. Panzavolta, K. Rubini. Relationship between triple-helix content and mechanical properties of gelatin films. Biomaterials 2004;25:5675-5680. [52] Eugene Khor. Methods for the treatment of collagenous tissues for bioprostheses (review). Biomaterials 1997;18:95-105. [53] Jayakrishnan A, Jameela SR. Glutaraldehyde as a fixative in bioprostheses and drug delivery matrices. Biomaterials 1996;17:471-484. [54] Korn AH, Feairheller SH, Filachione EM. Glutaraldehyde: nature of the reagent. J Mol Biol 1972;65:525-529. [55] Cheung DT, Nimni ME. Mechanism of crosslinking of proteins by glutaraldehyde. II: Reaction with monomeric and polymeric collagen. Connect Tissue Research 1982;10:201-216. [56] Weadock K, Olson RM, Silver FH. Evaluation of collagen crosslinking techniques. Biomater Med Dev Artif Organs 1983/84;11:293-318. [57] Lloyd DR, Burns CM. Coupling of acrylic polymers and collagen by use of a water-soluble carbodiimide. II. Investigations of the coupling mechanism. J Polym Sci: Polym Chem Ed 1979;17:3475-3483. [58] Kato YP, Christiansen DL, Hahn RA, Shieh SJ, Goldstein JD, Silver FH. Mechanical properties of collagen fiber: a comparison of reconstituted and rat tail fibers. Biomaterials 1989;10:38-42. [59] Tu R, Lu CL, Thyagarajan K. Kinetic study of collagen fixation with polyepoxy fixatives. J Biomed Mater Res 1993;27:3-9. [60] Chvapil M, Speer DP, Holubec H, Chvapil TA, King DH. Collagen fiber as a temporary scaffold for replacement of ACL in goats. J Biomed Mater Res 1993;27:313-325. [61] Naimark WA, Pereira CA, Tsang K, Lee JM. HMDC crosslinking of bovine pericardial tissue: a potential role of the solvent environment in the design of bioprosthetic materials. J Mater Sci Mater Med 1995;6:235-241. [62] Peraira CA, Lee JM, Haberer SA. Effect of alternative crosslinking methods on the low strain rate viscoelastic properties of bovine pericardial bioprosthetic material. J Biomed Mater Res 1990;24:345-361. [63] 陳煌鈞譯.材料科學與工程. 曉園出版社. [64] B. D. Ratner, A. S. Hoffman, F. J. Schoen, J. E. Lemons. Biomaterials Science: An introduction to materials in medicine. Academic Press 1996. [65] Nicole J. Einerson, Kelly R. Stevens, Weiyuan John Kao. Synthesis and physicochemical analysis of gelatin-based hydrogels for drug carrier matrices. Biomaterials 2002;24:509-523. [66] K. L. Carraway, D. E. Koshland. Carbodiimide modification of proteins. Methods in enzymol 1972;25:616-623. [67] S. Sano, K. Kato, Y. Ikada. Introduction of functional groups onto the surface of polyethylene for protein immobilization. Biomaterials 1993;14(11):817-822. [68] Hye-Won Kang, Yasuhiko Tabata, Yoshito Ikada. Fabrication of porous gelatin scaffolds for tissue engineering. Biomaterials 1999;20:1339-1344. [69] 王正一主編. 醫學工程原理與應用. 正中書局. [70] 林峰輝. 醫學工程教科書大綱(5)--組織工程, 王正一主編. 教育部醫學工程科技教科書. [71] Ohnishi ST, Barr JK. A simplified method of quantitating protein using the biuret and phenol reagents. Anal Biochem 1978;86(1):193–200. [72] Tim Mosmann. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 1983;65(1-2):55-63. [73] Elias Amador, Lionel E. Dorfman, Warren E. C. Wacker. Serum lactic dehydrogenase: an analytical assessment of current assays. Clinical Chemistry 1963;9(4):391-399. [74] Frederick L. Hall, Paul Fernyhough, Douglas N. Ishii, P. Richard Vulliet. Suppression of nerve growth factor-directed neurite outgrowth in PC12 cells by sphingosine, an inhibitor of protein kinase C. Journal of Biological Chemistry 1988;263(9):4460–4466. [75] Dellon AL, Mackinnon SE. Selection of the appropriate parameter to measure neural regeneration. Ann Plast Surg 1989;23:197-202. [76] Kanaya F, Firrell JC, Breidenbach WC. Sciatic function index, nerve conduction tests, muscle contraction, and axon morphometry as indicators of regeneration. Plast Reconstr Surg 1996;98:1264-71. [77] Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg 1989;83:129-38. [78] Sobin LH. AFIP Laboratory Methods in Histotechnology. Washington: American Registry of Pathology 1992:102-104. [79] 孫逸民, 陳玉舜, 趙敏勳, 謝明學, 劉與鑑. 儀器分析. 全威圖書有限公司. [80] Galen W. Ewing. Instrumental methods of chemical analysis, 5th edition. McGraw-Hill Book Company, 1985. [81] Douglas A. Skoog, Jamis J. Leary. Principles of instrumental analysis, 4th edition. Harcourt Brace Jovanovich college Publisher, 1992. [82] P. G. Griffiths. Chemical infrared Fourier transform spectroscopy. John Wiley and Sons, Inc. 1975. [83] James F. Shackelford. Introduction to materials science for engineers, 5th edition. Prentice Hall International, Inc. 2000. [84] Feng-Huei Lin, Chun-Hsu Yao, Jui-Sheng Sun, Haw-Chang Liu, Chin-Wang Huang. Biological effects and cytotoxicity of the composite composed by tricalcium phosphate and glutaraldehyde cross-linked gelatin. Biomaterials 1998;19:905-917. [85] Bill George, Peter Mclntyre. Infrared Spectroscopy. John Wiley and Sons. [86] Wim Groenewoud. Characterisation of polymers by thermal analysis. Elsevier. [87] Brockes JP, Fields KL, Raff MC. Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. Brain Res. 1979 Apr 6;165(1):105-18. [88] Breitenbach A, Li YX, Kissel T. Branched biodegradable polyesters for parenteral drug delivery systems. J Control Release 2000;64:167-178. [89] Naofumi Chinen, Masao Tanihara, Miyako Nakagawa, Keiko Shinozaki, Eriko Yamamoto,Yutaka Mizushima, Yasuo Suzuki. Action of microparticles of heparin and alginate crosslinked gel when used as injectable artificial matrices to stabilize basic fibroblast growth factor and induce angiogenesis by controlling its release. J Biomed Mater Res 2003;67A:61-68. [90] Christian Zettler, Diana Christine McLeod Bridges, Xin-Fu Zhou, Robert Archer Rush. Detection of increased tissue concentrations of Nerve Growth Factor with an improved extraction procedure. Journal of Neuroscience Research 1996;46:581-594. [91] Takayuki Harada, Chikako Harada, Shinichi Kohsaka, Etsuko Wada, Kazuhiko Yoshida, Shigeaki Ohno, Hiroshi Mamada, Kohichi Tanaka, Luis F. Parada, Keiji Wada. Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. Journal of Neuroscience 2002;22:9228-9236. [92] Silvia Biocca, Antonino Cattaneo, Pietro Calissano. A macromolecular structure favouring microtubule assembly in NGF-differentiated pheochromocytoma cells (PC12). The EMBO Journal 1983;2:643-648. [93] Xiaoyun Xu, Hanry Yu, Shujun Gao, Hai-Quan Mao, Kam W. Leong, Shu Wang. Polyphosphoester microspheres for sustained release of biologically active nerve growth factor. Biomaterials 2002;23:3765-3772. [94] Hunter A, Archer CW, Walker PS, Blunn GW. Attachment and proliferation of osteoblasts and fibroblasts on biomaterials for orthopaedic use. Biomaterials 1995;16(4):287-95. [95] Bagambisa FB, Joos U. Preliminary studies on the phenomenological behaviour of osteoblasts cultured on hydroxyapatite ceramics. Biomaterials 1990;11(1):50-6. [96] Rajaraman R, Rounds DE, Yen SP, Rembaum A. A scanning electron microscope study of cell adhesion and spreading in vitro. Exp Cell Res 1974;88(2):327-39. [97] T. Rae. A study on the effects of particulate metals of orthopaedic interest on murine macrophages in vitro. Journal of Bone and Joint Surgery 1975;57B(4):444-450. [98] Slater TF, Sawyer B, Struli U. Studies on succinate-tetrazolium reductase system III, points of coupling of four different tetrazolium salts. Biochim Biophys Acta. 1963;77:383-93. [99] Taniuchi M, Clark HB, Johnson EM Jr. Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci U S A 1986;83(11):4094-8. [100] Ridley AJ, Davis JB, Stroobant P, Land H. Transforming growth factors-beta 1 and beta 2 are mitogens for rat Schwann cells. J Cell Biol 1989;109:3419-24. [101] Bosch EP, Zhong W, Lim R. Axonal signals regulate expression of glia maturation factor-beta in Schwann cells: an immunohistochemical study of injured sciatic nerves and cultured Schwann cells. J Neurosci 1989;9(10):3690-8. [102] Seilheimer B, Schachner M. Regulation of neural cell adhesion molecule expression on cultured mouse Schwann cells by nerve growth factor. EMBO J 1987;6(6):1611-6. [103] Kinam Park, Waleed S. W. Shalaby, Haesun Park. Biodegradable drug delivery systems. Biodegradable hydrogels for drug delivery 1993:189-232. [104] Silvio Varon, Junichi Nomura, E. M. Shooter. The isolation of the mouse nerve growth factor protein in a high molecular weight form. Biochemistry 1967;6(7):2202-2209. [105] Levi-Montalcini R, Hamburger C. A diffusiable agent of mouse sarcoma, producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo. J Exp Zool 1953;123:233-288. [106] Tischler AS, Greene LA. Nerve growth factor-induced process formation by cultured rat pheochromocytoma cells. Nature 1975;258:341-342. [107] Greene LA, Tischler AS. Establishment of a noradrenergic clonal line of rat adrenal phreochromocytoma cells which respond to nerve growth factor. Pro Natl Acad Sci USA 1976;73:2424-2428. [108] Peng X, Greene LA, Kaplan DR, Stephens RM. Deletion of a conserved juxtamembrane sequence in Trk abolishes NGF-promoted neuritogenesis. Neuron 1995;15:395-406. [109] Meek MF, den Dunnen WF, Schakenraad JM, Robinson PH. Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly(DL-lactide-ε-caprolactone) nerve guide, using walking-tract analysis and electrostimulation tests. Microsurgery 1999;19:247-53. [110] den Dunnen WF, van der Lei B, Robinson PH, Holwerda A, Pennings AJ, Schakenraad JM. Biological performance of a degradable poly(lactic acid-ε-caprolactone) nerve guide; influence of tube dimensions. J Biomed Mater Res 1995;29:757-66. [111] Navarro X, Rodriguez FJ, Labrador RO, Buti M, Ceballos D, Gomez N, Cuadras J, Perego G. Peripheral nerve regeneration through bioresorbable and durable nerve guides. J Pereph Nerv Syst 1996;1:53-64. [112] Madison RD, da Silva C, Dikkes P, Sidman RL, Chiu TH. Peripheral nerve regeneration with entubulation repair: comparison of biodegradable nerve guides versus polyethylene tubes and the effects of a laminin-containing gel. Exp Neurol 1987;95:378-90. [113] Favaro G, Bortolami MC, Cereser S, Dona M, Pastorello A, Callegaro L, Fiori MG. Peripheral nerve regeneration through a novel bioresorbable nerve guide. ASAIO Trans 1990;36:M291-4. [114] Aebischer P, Guenard V, Winn SR, Valentini RF, Galletti PM. Blind-ended semipermeable guidance channels support peripheral nerve regeneration in the absence of a distal nerve stump. Brain Res 1988;454:179-87. [115] Kulbatski I, Cook DJ, Tator CH. Calcium entry through L-type calcium channels is essential for neurite regeneration in cultured sympathetic neurons. J Neurotrauma 2004;21:357-74. [116] Mackinnon SE, Dellon AL, O’Brien JP. Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model. Muscle Nerve 1991;14:1116-22. [117] Munro CA, Szalai JP, Mackinnon SE, Midha R. Lack of association between outcome measures of nerve regeneration. Muscle Nerve 1998;21:1095-1097. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/38193 | - |
| dc.description.abstract | 本實驗以明膠為薄膜基材，發展出一個適用於神經修復的替代材料來取代現有的自體移植，並進行神經再生導管的研究。實驗分為三大部分：導管材料的發展、神經生長因子(NGF)的固定與體外生物相容性評估，以及導管植入坐骨神經之體內評估。首先在材料的研發上，我們比較了利用幾丁聚醣與明膠交聯的薄膜，以及添加三鈣磷酸鹽粉末以強化明膠機械強度的薄膜，分別進行紅外線光譜分析、微差掃描熱差分析、機械強度測試及水接觸角測試。結果顯示以低濃度戊二醛交聯及三鈣磷酸鹽粉末強化之明膠薄膜(GTG)為最適合用於神經再生導管的材料，其延性適中、機械強度佳且為較具親水性的材料。因此，在後續的實驗中將以GTG做為進行神經再生導管的材料。
在體外生物相容性評估的結果顯示，GTG薄膜無論表面有無NGF的固定皆不會對許旺氏細胞(Schwann cell)造成細胞毒性的影響。此外，GTG薄膜表面固定NGF分子(GEN) 證實有較多的許旺氏細胞貼附，而使用物理性吸附的薄膜由於大部分NGF已被清洗掉，所以並沒有增加細胞貼附的作用，雖然GTG薄膜固定NGF分子並不能促進許旺氏細胞的增生，但GEN薄膜可以促進許旺氏細胞的貼附；而在NGF的釋放實驗中證實，GEN薄膜可以持續釋放NGF至少60天，且其最低釋放量亦達刺激PC12細胞的最小濃度。另外，在PC12細胞的培養中發現GEN組神經突的生長數量較GTG組高，顯示GEN薄膜釋放出的NGF具有刺激PC12細胞分化的生物活性。 在神經導管植入大鼠坐骨神經的體內評估中顯示，GTG及GEN薄膜的降解速度適中，在神經修復完成前導管仍可提供一個管腔支持神經軸突生長。而在GEN導管內培養許旺氏細胞的GENSc組所再生的神經纖維有較緻密的軸突生長，組織間只有細小的裂隙，橫切面面積也較其他組的面積大。在電生理的實驗中也證實其再生的神經軸突之電傳導功能恢復指數較其他組為高，坐骨神經的運動功能也有相當程度的恢復。因此，本實驗使用之GEN導管結合許旺氏細胞的培養，具有相當好的潛力發展為用於人體的神經再生導管，以修復受損之周邊神經。 | zh_TW |
| dc.description.abstract | In order to develop a nerve regenerated guidance channel, we used gelatin membrane to substitute for nerve autograft. The studies were divided into three parts, including the development of materials, biocompatibility tests (in vitro) of membranes immobilized with nerve growth factor (NGF) and in vivo tests of guidance channel. At the first, we used chitoson cross-linked with gelatin to compare with gelatin-tricalcium phosphate membranes by Fourier-transform infrared spectrophotometer (FTIR) analysis, differential scanning calorimetry (DSC) measurement, mechanical test and water contact angle evaluation. The results indicated that the gelatin-tricalcium phosphate membranes cross-linking with 0.05% glutaraldehyde solution (GTG) were suitable for nerve guidance channels. The ductility, mechanical strength and hydrophilic property of GTG were all good for nerve repair. Therefore, GTG membranes were used for the later experiments.
The results of in vitro study showed that the GTG composite, whether cross-linking with NGF or not, had no cytotoxic effect to Schwann cell culture. Comparing the GTG membrane immobilized with NGF (GEN) and GTG soaked in NGF solution without carbodiimide (GN composite) as cross-linking agent, the data confirmed more attachment of Schwann cells onto GEN composite. Although GTG cross-linking with NGF did not promote Schwann cell proliferation, the techniques we used in this study provided a method to fabricate a novel biomaterial incorporation with Schwann cells and covalently immobilized NGF. Besides, GEN membrane sustained released NGF at least 60 days, and the minimum amount of NGF released from GEN reached the concentration to stimulate PC12 cell differentiation. PC 12 cells showed significant neurite outgrowth on GEN membranes which was statistically higher than GTG without NGF immobilization. From these experiments, it can be concluded that the NGF immobilizing onto GTG membrane remaining the bioactivity. The results of in vivo study indicated that the degradation rate of GTG and GEN membranes were moderate for nerve regeneration. The regenerated nerve fiber in GEN guidance channel cultured with Schwann cell (GENSc) showed denser nerve tissue, and the cross-section area of axon were larger than other groups. The histomorphometric, electrophysiologic, and functional assessments demonstrated that axon in GENSc recovered batter than other groups. Therefore, GEN guidance channel incorporated with Schwann cell can be a potential candidate for human peripheral nerve repair. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T16:27:45Z (GMT). No. of bitstreams: 1 ntu-94-F89548002-1.pdf: 11302307 bytes, checksum: 3c28fa2f61a3709d8798b9325af54408 (MD5) Previous issue date: 2005 | en |
| dc.description.tableofcontents | 誌謝
中文摘要 英文摘要 第一章 緒論 1-1 前言…………………………………………………………………1 1-2 研究目的……………………………………………………………3 1-3 神經再生導管之研究發展…………………………………………5 1-3-1 修復的方式………………………………………………………5 1-3-2 材料發展…………………………………………………………6 1-3-3 神經生長因子及許旺氏細胞於神經修復的重要性……………9 第二章 理論基礎 2-1 神經系統及神經修復生理學簡介…………………………………13 2-1-1 神經系統簡介……………………………………………………13 2-1-2 神經修復生理學簡介……………………………………………19 2-2 強化基材機械性質之方法與原理…………………………………21 2-2-1 明膠分子鏈間的交聯鍵結………………………………………21 2-2-2 顆粒強化複合材料………………………………………………26 2-3 生醫材料表面固定生物分子之方法與原理………………………28 2-3-1 物理吸附法………………………………………………………28 2-3-2 膠體包埋法………………………………………………………29 2-3-3 共價鍵結法………………………………………………………29 2-4 材料評估方法與原理………………………………………………31 2-4-1 體外生物相容性評估……………………………………………31 2-4-2 體內評估…………………………………………………………34 第三章 材料與方法 3-1 實驗藥品與儀器……………………………………………………36 3-1-1 實驗藥品與耗材…………………………………………………36 3-1-2 實驗儀器設備…………………………………………………..37 3-1-3 簡寫符號表………………………………………………………40 3-2 實驗流程……………………………………………………………41 3-3 實驗薄膜之製備與評估……………………………………………42 3-3-1 實驗步驟…………………………………………………………42 3-3-2 材料分析方法……………………………………………………46 3-4 神經生長因子的固定與體外評估…………………………………49 3-4-1 實驗步驟…………………………………………………………49 3-4-2 許旺氏細胞播種於材料表面之相容性評估……………………50 3-4-2-1 許旺氏細胞之型態評估………………………………………51 3-4-2-2 GTG薄膜之生物相容性評估………………………………...51 3-4-3 神經生長因子的釋放分析………………………………………54 3-4-3-1 固定濃度測試…………………………………………………54 3-4-3-2 釋放速率及釋放機制測試……………………………………54 3-4-3-3 體外評估NGF之生物活性及細胞相容性…………………...55 3-5 人工神經導管植入大鼠坐骨神經之體內評估……………………59 3-5-1 實驗步驟…………………………………………………………59 3-5-2 體內植入之測試評估……………………………………………61 第四章 實驗結果與討論 4-1 實驗薄膜之材料分析評估…………………………………………64 4-1-1 傅立葉轉換紅外線光譜儀分析(FT/IR)……………………….64 4-1-2 微差掃描熱差分析(DSC)……………………………………….68 4-1-3 機械強度測試--拉伸測試………………………………………72 4-1-4 水接觸角測量……………………………………………………79 4-2 神經生長因子的固定與體外評估…………………………………83 4-2-1 許旺氏細胞播種於材料表面之評估……………………………83 4-2-1-1 許旺氏細胞的體外培養………………………………………83 4-2-1-2 許旺氏細胞與材料之相容性…………………………………86 4-2-2 神經生長因子的釋放分析………………………………………91 4-2-2-1 固定濃度測試…………………………………………………91 4-2-2-2 釋放速率………………………………………………………93 4-2-2-3 體外評估NGF之生物活性及細胞相容性…………………….97 4-3 人工神經導管植入大鼠坐骨神經之體內評估………………….104 4-3-1 坐骨神經功能指數分析……………………………………….104 4-3-2 複合肌肉動作電位…………………………………………….109 4-3-3 組織型態評估………………………………………………….116 第五章 結論……………………………………………………….129 第六章 參考文獻………………………………………………….131 附錄 作者簡介…………………………………………………………141 圖目錄 圖1-1 神經再生導管示意圖……………………………………………4 圖2-1 神經元的型態構造………………………..……………………14 圖2-2 各類神經膠細胞的型態…………………………………………16 圖2-3 許旺氏細胞的構造………………………………………………18 圖2-4 神經修復機制之示意圖…………………………………………20 圖2-5 戊二醛與明膠之胺基交聯反應之作用機制……………………22 圖2-6 carbodiimde交聯明膠之反應機制…………………………….23 圖2-7 環氧化物交聯明膠之反應機制…………………………………24 圖2-8 HMDI交聯明膠之反應機制………………………………………25 圖2-9複合材料可分為三大類：(1)顆粒型複合材料，(2)纖維複合材料與(3)層狀複合材料………………………………………………….26 圖2-10 (A)不具顆粒散佈的材料，在應力作用下裂縫(crack)直接貫穿材料。(B)顆粒強化材料，其散佈的顆粒可以阻擋裂縫繼續產生。………………...…….…................................27 圖2-11 細胞內蛋白質含量之測試反應圖…………………………….32 圖2-12 活細胞代謝產生formazan之反應圖………………………….32 圖2-13 LDH之測試反應圖………………………………………………33 圖3-1 FTIR的組件示意圖………………………………………………37 圖3-2 實驗流程…………………………………………………………41 圖3-3 實驗薄膜之製備與評估之流程圖………………………………45 圖3-4 薄膜拉伸試片標準尺寸…………………………………………47 圖3-5 材料分析流程圖…………………………………………………48 圖3-6 carbodiimide固定神經生長因子之反應機制…………………49 圖3-7 NGF的固定與體外評估流程圖………………………………….58 圖3-8 神經導管接枝手術後的坐骨神經………………………………60 圖3-9 植入大鼠坐骨神經體內評估之流程圖…………………………63 圖4-1 明膠(Gel)、幾丁聚醣(Cs)和明膠-幾丁聚醣共聚合物(Cs-Gel)的傅立業轉換紅外線光譜………………………………………………66 圖4-2 明膠(Gel)、幾丁聚醣(Cs)、三鈣磷酸鹽-明膠(GTG) 和三鈣磷酸鹽-明膠-幾丁聚醣共聚合物(Cs-GTG)四種薄膜的傅立業轉換紅外線光譜………………..........................................67 圖4-3 Cs、Gel及Cs-Gel薄膜的DSC熱分析之溫度記錄曲線圖………70 圖4-4 Gel、Cs、GTG及Cs-GTG薄膜的DSC熱分析之溫度記錄曲線圖.71 圖4-5 幾丁聚醣(Cs)薄膜的應力-應變曲線………………………….74 圖4-6 明膠(Gel)薄膜的應力-應變曲線………………………………74 圖4-7 幾丁聚醣-明膠(Cs-Gel)薄膜的應力-應變曲線………………75 圖4-8 明膠-三鈣聯酸鹽(GTG)薄膜的應力-應變曲線……………….75 圖4-9 幾丁聚醣-明膠-三鈣聯酸鹽(Cs-GTG)薄膜的應力-應變曲線.76 圖4-10 五種實驗薄膜的最大應力及斷裂應變……………………….77 圖4-11 各組薄膜的楊氏模數………………………………………….77 圖4-12 各組薄膜之水接觸角照片…………………………………….80 圖4-13 五組實驗試片之水接觸角測量值…………………………….81 圖 4-14 光學顯微鏡下原代培養的許旺氏細胞型態觀察……………84 圖4-15 許旺氏細胞在培養盤上原代培養的型態…………………….84 圖4-16 SEM觀察許旺氏細胞在GEN薄膜上培養7天後的細胞型態……85 圖4-17 許旺氏細胞在GTG薄膜上培養7天後之情形………………….85 圖4-18 許旺氏細胞在不同的薄膜上培養1, 3, 7天後之蛋白質含量的結果...….................................................89 圖4-19 許旺氏細胞培養之LDH活性分析………………………………89 圖4-20 許旺氏細胞培養在不同的薄膜上之MTT活性測試……………90 圖4-21 以不同濃度的NGF溶液固定NGF分子在GTG薄膜表面所測得之NGF的固定量。………………………………………………………….92 圖4-22 GEN薄膜在體外60天釋出NGF的累積釋放量………………….96 圖4-23 平均每日GEN薄膜在體外的NGF釋放量……………………….96 圖4-24 PC12細胞在培養1, 3及7天後的蛋白質含量分析………….100 圖4-25 PC12細胞在培養1, 3及7天後的MTT還原活性分析…………100 圖4-26 PC12細胞在培養1, 3及7天後的LDH活性分析………………101 圖4-27 PC12細胞在與GTG及GEN薄膜共養下的細胞型態……………102 圖4-28 神經突生長細胞的數量………………………………………103 圖4-29 在神經導管接枝手術後之大鼠，在木製步道上行走。……106 圖4-30 測量足跡的三種參數…………………………………………106 圖4-31 坐骨神經功能指數分析(Sciatic function index, SFI)…………………….........................................107 圖4-32 神經手術後6週至12週的SFI進步值…………………………108 圖4-33 神經導管手術24週後GTG組的複合肌肉動作電位(CMAP)結果….....................................................111 圖4-34 神經導管手術24週後silicone組的複合肌肉動作電位(CMAP)結果…...................................................112 圖4-35 神經導管手術24週後GEN組的複合肌肉動作電位(CMAP)結果……...................................................113 圖4-36 神經導管手術24週後GENSc組的複合肌肉動作電位(CMAP)結果….....................................................114 圖4-37 神經導管手術24週後之CMAP功能恢復指數…………………115 圖4-38 (A)手術24週後植入之GTG神經導管與組織的沾黏情形，以及(B) 植入生物體內24週後GTG材料在生物體內的降解情形。………119 圖4-39 手術24週後植入之silicone神經導管與組織的沾黏情形。120 圖4-40 (A)手術24週後植入之GEN神經導管與組織的沾黏情形，以及(B) 植入生物體內24週後GEN材料在生物體內的降解情形。………121 圖4-41 (A)手術24週後植入之GENSc神經導管與組織的沾黏情形，以及(B) 植入生物體內24週後GENSc材料在生物體內的降解情形。…122 圖4-42 (A) 光學顯微鏡觀察神經修復24週後GTG神經導管中間段的橫切面(100X)，(B)顯示橫切面的部分區域放大照片(400X)。………123 圖4-43 (A) 光學顯微鏡觀察神經修復24週後silicone神經導管中間段的橫切面(100X)，(B)顯示橫切面的部分區域放大照片(400X)。124 圖4-44 (A) 光學顯微鏡觀察神經修復24週後GEN神經導管中間段的橫切面(100X)，(B)顯示橫切面的部分區域放大照片(400X)。………125 圖4-45 (A)光學顯微鏡觀察神經修復24週後GENSc神經導管中間段的橫切面(100X)，(B)顯示橫切面的部分區域放大照片(400X)。……126 圖4-46 神經修復24週後四組神經導管內的神經纖維中間段截面積的評估…...................................................127 表目錄 表2-1 神經系統…………………………………………………………15 表2-2 神經膠細胞的種類與功能………………………………………16 表4-1 Gel、Cs、Cs-Gel、GTG及Cs-GTG薄膜的Tg值及Tm值…………71 表4-2 實驗薄膜的機械性質……………………………………………78 | |
| dc.language.iso | zh-TW | |
| dc.title | 三鈣磷酸鹽強化之明膠基材表面固定神經生長因子及培養許旺氏細胞用於周邊神經再生導管之研究 | zh_TW |
| dc.title | A Study of Gelatin-Tricalcium Phosphate Membranes Immobilized with Nerve Growth Factors and Incorporated Schwann Cells as Guidance Channels for Peripheral Nerve Regeneration | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 93-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 金重勳,廖峻德,郭士民,姚俊旭,謝松蒼 | |
| dc.subject.keyword | 神經再生導管,神經生長因子,許旺氏細胞,生物相容性,體內評估, | zh_TW |
| dc.subject.keyword | nerve regenerated guidance channel,nerve growth factor,Schwann cell,biocompatibility,in vivo test, | en |
| dc.relation.page | 140 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2005-07-14 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| Appears in Collections: | 醫學工程學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-94-1.pdf Restricted Access | 11.04 MB | Adobe PDF |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.