研究生: |
許家寧 Chia-Ning Hsu |
---|---|
論文名稱: |
積層製造生物可降解Poly(glycerol sebacate) acrylate/Poly(ethylene glycol) diacrylate神經導管之研究 Additive manufacturing biodegradable Poly(glycerol sebacate) acrylate/Poly(ethylene glycol) diacrylate nerve conduit |
指導教授: |
鄭逸琳
Yih-Lin Cheng |
口試委員: |
謝明佑
Ming-You Shie 何明樺 Ming-Hua Ho |
學位類別: |
碩士 Master |
系所名稱: |
工程學院 - 機械工程系 Department of Mechanical Engineering |
論文出版年: | 2020 |
畢業學年度: | 108 |
語文別: | 中文 |
論文頁數: | 139 |
中文關鍵詞: | 神經管組織工程 、微溝槽結構 、PGSA 、PEG-DA 、降解性質 、拉伸強度 |
外文關鍵詞: | Neural Tube Tissue Engineering, Microgroove Structure, PGSA, PEG-DA, Degradation Properties, Tensile Strength |
相關次數: | 點閱:572 下載:0 |
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目前使用生醫材料來製作神經管的材料大部分是使用矽膠管,雖然矽膠製神經管具有高生物適應性及高柔軟度的優點,但不易被生物體降解。且過去研究中發現微溝槽表面可以最有效地引導許旺氏細胞和神經元的生長,但因為製程上的困難無法製作精度較高的導管。因此本研究將使用DLP製程來製作具有微溝槽結構可降解之神經導管。
使用DLP製程可以有效簡化過去製作一個神經管所需的多個生產技術,可製作尺寸微小的微溝槽結構。材料方面挑選PGSA及PEG-DA作為可降解神經導管主材料,對其進行降解試驗與拉伸試驗。結果顯示PGSA與PEG-DA混和材料具有降解性的同時具有一定的機械強度。另外發現當材料PGSA60+PEGDA=1:1另外添加15%PEG後的降解百分率可提升為原先的3倍。此外,細胞培養觀察到細胞在PGSA30+PEGDA=1:2 PATTERN支架上生長狀況佳、能均勻分布,且細胞沿著微溝槽的方向排列、生長。最後,老鼠動物實驗證明神經導管具有生物相容性,且具備足夠機械強度能真正實際運用在生物體上,使受傷之神經管進行再生與修復。
At present, most of the materials used to make nerve conduit using biomedical materials are silicone conduits. Although silicon nerve conduit are high biocompatibility and high softness, but they are not easily degraded. And in the past research, it was found that the surface of microgrooves can most effectively guide the growth of Schwann cells. Therefore, this study will use the DLP process to fabricate degradable nerve conduit with microgroove structures.
Using the DLP process produce micro-groove structures with small dimensions. PGSA and PEG-DA were selected as the main materials of the degradable nerve conduit, and degradation tests and tensile tests were performed on them. The results show that the PGSA and PEG-DA mixed materials are degradable and have certain mechanical strength. It was also found that when the material PGSA60 + PEGDA = 1: 1 and the addition of 15% PEG, the degradation percentage could be increased by three times. In addition, in cell culture, it was observed that the cells grew well on the PGSA30 + PEGDA = 1: 2 PATTERN scaffold and could be evenly distributed, and the cells were arranged and grown along the direction of the micro grooves. In the end, rat animal experiments proved that the nerve conduit are biocompatible and have sufficient mechanical strength to be used in living organisms to regenerate and repair injured nerve conduit.
[1] Lee, S. K., & Wolfe, S. W. (2000). Peripheral nerve injury and repair. JAAOS-Journal of the American Academy of Orthopaedic Surgeons, 8(4), 243-252.
[2] Millesi, H., Meissl, G., & Berger, A. (1976). Further experience with interfascicular grafting of the median, ulnar, and radial nerves. The Journal of bone and joint surgery. American volume, 58(2), 209-218.
[3] Mitchel, J. A., & Hoffman-Kim, D. (2011). Cellular scale anisotropic topography guides Schwann cell motility. PloS one, 6(9).
[4] Liu, C., Xia, Z., & Czernuszka, J. (2007). Design and development of three-dimensional scaffolds for tissue engineering. Chemical Engineering Research and Design, 85(7), 1051-1064.
[5] Becker, C., & Jakse, G. (2007). Stem cells for regeneration of urological structures. European urology, 51(5), 1217-1228.
[6] 宋信文 梁晃千,2003,“建立人類的身體工房-組織工程”, 科學發展第362期。
[7] 楊婷琪,2002,“組織工程的重要元件-生物分子”,工研院經貿中心生醫組。
[8] 廖俊仁,2002,“組織工程用多孔隙骨架材料”,工研院生醫工程中心。
[9] Yang, S., Leong, K.-F., Du, Z., & Chua, C.-K. (2001). The design of scaffolds for use in tissue engineering. Part I. Traditional factors. Tissue engineering, 7(6), 679-689.
[10] Dixon, A. R., Jariwala, S. H., Bilis, Z., Loverde, J. R., Pasquina, P. F., & Alvarez, L. M. (2018). Bridging the gap in peripheral nerve repair with 3D printed and bioprinted conduits. Biomaterials, 186, 44-63.
[11] 蔡秉宏,1999,“以聚殼醣合成光交聯性衍生物之探討”,國立成功大學化學工程研究所,碩士論文。
[12] Marcel Dekker, D. S. (1994). Medical application of synthetic polymers. NewYork, 725.
[13] Park, J. S., Woo, D. G., Sun, B. K., Chung, H.-M., Im, S. J., Choi, Y. M., Park, K.-H. (2007). In vitro and in vivo test of PEG/PCL-based hydrogel scaffold for cell delivery application. Journal of Controlled Release, 124(1-2), 51-59.
[14] Gao, J., Crapo, P. M., & Wang, Y. (2006). Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering. Tissue engineering, 12(4), 917-925.
[15] Wang, J., Boutin, K. G., Abdulhadi, O., Personnat, L. D., Shazly, T., Langer, R., Borenstein, J. T. (2013). Fully Biodegradable Airway Stents Using Amino Alcohol‐Based Poly (ester amide) Elastomers. Advanced healthcare materials, 2(10), 1329-1336.
[16] Nijst, C. L., Bruggeman, J. P., Karp, J. M., Ferreira, L., Zumbuehl, A., Bettinger, C. J., & Langer, R. (2007). Synthesis and characterization of photocurable elastomers from poly (glycerol-co-sebacate). Biomacromolecules, 8(10), 3067-3073.
[17] 陳俊佑,2018,“探討光固化生物可分解高分子PGSA、PEGDA和PCLDA共聚材料之物理與降解性質”, 國立清華大學化學工程學系所,碩士論文。
[18] wiki. NSdiagram https://commons.wikimedia.org/wiki/File:NSdiagram.png#filehistory. 2002.
[19] Chen, Q.-Z., Bismarck, A., Hansen, U., Junaid, S., Tran, M. Q., Harding, S. E., Boccaccini, A. R. (2008). Characterisation of a soft elastomer poly (glycerol sebacate) designed to match the mechanical properties of myocardial tissue. Biomaterials, 29(1), 47-57.
[20] 陳建璋,2018,“3D列印聚氨酯導管結合許旺氏細胞團塊於周邊神經再生的應用評估”(碩士) ,中國醫藥大學生物醫學工程所,碩士論文。
[21] Chiono, V., & Tonda-Turo, C. (2015). Trends in the design of nerve guidance channels in peripheral nerve tissue engineering. Progress in neurobiology, 131, 87-104.
[22] Lee, S. K., & Wolfe, S. W. (2000). Peripheral nerve injury and repair. JAAOS-Journal of the American Academy of Orthopaedic Surgeons, 8(4), 243-252.
[23] Melchels, F. P., Feijen, J., & Grijpma, D. W. (2010). A review on stereolithography and its applications in biomedical engineering. Biomaterials, 31(24), 6121-6130.
[24] Widmer, M. S., Gupta, P. K., Lu, L., Meszlenyi, R. K., Evans, G. R., Brandt, K., Mikos, A. G. (1998). Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration. Biomaterials, 19(21), 1945-1955.
[25] Evans, G., Brandt, K., Widmer, M., Lu, L., Meszlenyi, R., Gupta, P., Gürlek, A. (1999). In vivo evaluation of poly (L-lactic acid) porous conduits for peripheral nerve regeneration. Biomaterials, 20(12), 1109-1115.
[26] Radulescu, D., Dhar, S., Young, C. M., Taylor, D. W., Trost, H.-J., Hayes, D. J., & Evans, G. R. (2007). Tissue engineering scaffolds for nerve regeneration manufactured by ink-jet technology. Materials Science and Engineering: C, 27(3), 534-539.
[27] Arcaute, K., Mann, B. K., & Wicker, R. B. (2011). Fabrication of off-the-shelf multilumen poly (ethylene glycol) nerve guidance conduits using stereolithography. Tissue Engineering Part C: Methods, 17(1), 27-38.
[28] Pateman, C. J., Harding, A. J., Glen, A., Taylor, C. S., Christmas, C. R., Robinson, P. P., . . . Haycock, J. W. (2015). Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair. Biomaterials, 49, 77-89.
[29] 謝浚雄,2011,“光聚合PCL材料系統成份探討及其應用於快速成型3D組織工程支架”,國立台灣科技大學機械工程研究所,碩士論文。
[30] 孫凱閔,2011,“PCL結合PEG-acrylate透過動態光罩成型系統製作3D多孔性組織工程支架”,國立台灣科技大學機械工程研究所,碩士論文。
[31] 侯佳延,2012,“PCL結合PEG-diacrylate透過反射式動態光罩成型系統製作3D多孔性組織工程支架”,國立台灣科技大學機械工程研究所,碩士論文。
[32] 楊淯凱,2013,“以積層製造技術光固化PCL-PEG-diacrylate之材料性質與組織工程支架成型性探討”,國立台灣科技大學機械工程研究所,碩士論文。
[33] 魏廷宇,2015,“以材料染色改善光固化PCL-DA/PEG-DA支架精度之研究”,國立台灣科技大學機械工程研究所,碩士論文。
[34] 許淯維,2016,“使用積層製造技術製作光固化PCL-DA+PEG-DA/PGSA支架應用於肝組織工程之研究”,國立台灣科技大學機械工程研究所,碩士論文。
[35] 杜睿恩,2017,“可光固化poly(glycerol sebacate) acrylate +poly(ε-caprolactone) diacrylate製備新型支架應用於肝組織工程之研究”,國立台灣科技大學機械工程研究所,碩士論文。
[36] 洪睿廷,2017,“使用積層製造技術製作光固化Poly(ε-caprolactone) diacrylate /Poly(ethyleneglycol) diacrylate/ Poly(glycerol sebacate) acrylate血氧交換結構之研究”,國立台灣科技大學機械工程研究所,碩士論文。
[37] 吳沛頡,2018,“使用積層製造技術製作光固化雙生醫材料支架應用於組織工程”,國立台灣科技大學機械工程研究所,碩士論文。
[38] Borschel, G. H., Kia, K. F., Kuzon Jr, W. M., & Dennis, R. G. (2003). Mechanical properties of acellular peripheral nerve. Journal of Surgical Research, 114(2), 133-139.
[39] Brushart, T. M., Mathur, V., Sood, R., & Koschorke, G.-M. (1995). Dispersion of regenerating axons across enclosed neural gaps. The Journal of hand surgery, 20(4), 557-564.
[40] Yao, L., de Ruiter, G. C., Wang, H., Knight, A. M., Spinner, R. J., Yaszemski, M. J., Pandit, A. (2010). Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit. Biomaterials, 31(22), 5789-5797.