目前組織工程仍以單材料支架作為體外細胞培養，但因細胞生長的需求，缺乏養份、氧氣及蛋白質等導致培養過程中無法模擬實際人體之微環境。透過不同材料特性的結合，製備出一種生醫支架可配合不同之細胞種類並提供所需的功能性環境，因此，本研究建立雙材料DLP成型系統，針對不同材料的接合效果以及雙材料支架對於細胞培養作進一步探討。
使用DLP製程製作出具有高精度之雙材料生醫支架並加裝換槽機構讓列印過程更換材料時，整體水平位置的定位更加準確，避免機台的震動造成成型效果不佳。材料部分挑選出PGSA60+PCL-DA及PEG-DA，分別測試材料之間的性質差異。在列印過程中發現界面層間隙及缺陷的產生，造成接合面上應力集中及附載能力降低，經實驗發現將接合面之材料PEG-DA固化深度提升至140μm可有效增加界面層之接合能力並印製出具有不同材料且高精度之生醫支架。透過植入人類肝細胞(Hepatocyte)與人類靜脈內皮細胞(HUVECs)至生醫支架中細胞培養，發現培養過程中細胞與細胞間保有良好的生物相容性。此外，為了可以增加血管材料PEG-DA浸泡於水中的穩定性及物質擴散能力，因此加入了PGSA來調配出適當的材料，未來可望藉由此製程及材料提供更廣泛的應用於生醫組織工程。

At present, tissue engineering still uses single-material scaffold for vitro cell culture, but lack of the nutrients, oxygen and protein in cell growth causes the micro-environment can’t simulate the human body. By the combination of different material properties, a scaffold can be prepared to match different cell types and provide the functional environment. Therefore, this study established a multiple-material DLP system, research the bonding effect of different materials, and study on multi-material scaffold for cell culture.
The DLP process is applied to produce a multiple-material scaffold with high precision and install a tank-changing mechanism is more convenient to change the material in the printing process to avoid the vibration of the machine.PGSA60+PCL-DA and PEG-DA were selected to test the difference in properties between the materials. The gap of interface and defect were found during the printing process, resulting in stress concentration and reduced loading capacity. It has been found that the curing depth of the bonding surface PEG-DA to 140 μm can effectively increase the bonding ability and print a precised scaffold with different materials.Through the implantation of Hepatocyte and HUVECs into the scaffold, it was found that the cells maintained good biocompatibility during the culture. In addition, in order to increase the stability of vascular material PEG-DA immersion in water and the ability of molecular diffusion, PGSA has been added to formulate, and it is expected that the process and materials will be more widely application in in the tissue engineering.

[1] Shanjani, Y., Pan C.C., Elomaa, L., and Yang, Y. (2015). “A Novel Bioprinting Method and System for Forming Hybrid Tissue Engineering Constructs.” Biofabrication 7(4).
[2] 陳蘊函，2017，“多色多功能光固化3D列印系統研發”，國立臺灣科技大學機械工程研究所，碩士論文.
[3] 吳文政，“接著劑的原理“ https://goo.gl/wQ49vr
[4] 彭公秋、楊進軍、曹正華、謝富原，2011，“T700S/QY8911 複合材料界面匹配研究.” Journal oF Aeronautical Materials 31(2):43-48.
[5] Kietzman, J.W., and Prinz F.B. “Material Strength in Polymer Shape Deposition Manufacturing.” Department of Mechanical Engineering Stanford University, Stanford, California: 567-574.
[6] Liu, C., Xia, Z., Czernuszka J.T. (2007) “Design and Development of Three-Dimensional Scaffolds for Tissue Engineering.” Chemical Engineering Research and Design 85(7):1051-1064.
[7] Becker, C., Jakse, G. (2007) “Stem Cells for Regeneration of Urological Structures.” European Urology 51(5):1217-1228.
[8] 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，6-11.
[9] 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.
[10] 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.
[11] Yang, S., Leong K.F., Du, Z., Chua, C.K. (2001) “The Design of Scaffolds for Use in Tissue Engineering. Part I. Traditional factors.” 7(6):679-689.
[12] 許芳豪，2006，“以快速原型技術研究組織工程支架孔徑大小對細胞成長之影響”，國立臺灣科技大學機械工程研究所，碩士論文.
[13] Kweon, H.Y., Yoo, M.K.,Park, I.K., Kim, T.H., Lee, H.C., et al. (2003) “A novel degradable polycaprolactone networks for tissue engineering”Biomaterials 24(5):801-808.
[14] Gao, J., Crapo, P.Y., Wang M.D. (2006) “Macroporous Elastomeric Scaffolds with Extensive Micropores for Soft Tissue Engineering” Tissue Engineering12(4):917-925.
[15] Wang, J., Boutin, K.G., Abdulhadi, O., Personnat, L.D., Shazly, T., Langer, R., et al. (2013) “Fully Biodegradable Airway Stents Using Amino Alcohol-BasedPoly(ester amide) Elastomers” Advanced healthcare materials 2(10):1329-1336.
[16] Nijst, C.L.E., 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:3067-3073.
[17] Chen, Q.Z., Bismarck, A., Hansen, U., Junaid, S., Tran, M.Q., Harding, S.E., et al. (2008) “Characterisation of A Soft Elastomer Poly(glycerol sebacate) Designed to Match the Mechanical Properties of Myocardial Tissue” Biomaterials:29(1)47-57.
[18] Saadi, T., Nayshool, O., Carmel, J., Ariche, A., Bramnik, Z. (2014) “Cellularized biosynthetic microhydrogel polymersfor intravascular liver tissue regeneration therapy.” Tissue Engineering. Part A 20(21-22):2850-2859.
[19] Kasuya J., Sudo, R., Tamogami, R., Masuda, G., Mitaka, T. “Reconstruction of 3D Stacked Hepatocyte Tissuesusing Degradable, Microporous Poly (D,L-lactide-co-glycolide)Membranes.” Biomaterials 33(9):2693-2700.
[20] Vogler, E.A. (1998) “Structure and Reactivity of Water at Biomaterialsurfaces.” Advances in Colloid and Interface Science 74(1–3):69-117.
[21] Bockhorn, M., Goralski, M., Prokofiev, D., Dammann, P., Grunewald, P., Trippler, M., et al. (2007) “VEGF is Important for Early Liver Regeneration After Partial Hepatectomy.” Journal of Surgical Research 138(2):291-299.
[22] Kulig, K.M., Vacanti, J.P. (2004) “Hepatic Tissue Engineering.” 12(3-4):303-310.
[23] Ko, H. C. H., Milthorpe B.K., and McFarland C.D. (2007) “Engineering thick tissues - the vascularisation problem.” European Cells and Materials(14):1-19.
[24] Freyer, N., Greuel, S., Knospel, F., Strahl, N., Amini, L., Jacobs, F., Monshouwer, M., and Zeilinger, K. (2017). “Effects of Co-Culture Media on Hepatic Differentiation of hiPSC with or without HUVEC Co-Culture.” International Journal Molecular Sciences 18(8):1724.
[25] Kirkpatrick, C.J., Fuchs, S., Unger, R.E. (2011). “Co-culture System for Vascularization-Learning from Nature.” Advanced Drug Delivery Reviews 63:291-299.
[26] Novik, E.I., Dwyer, J., Morelli, J.K., Parekh, A., Cho, C., Pludwinski, E., et al. (2017) “Long-enduring Primary Hepatocyte-based Co-cultures Improve Prediction of Hepatotoxicity” Toxicology and Applied Pharmacology 336:20-30.
[27] Chen, Q.Z., Bismarck, A., Hansen, U., Junaid, S., Tran, M.Q., Harding, S.E., et al. (2008) “Characterisation of A Soft Elastomer Poly(glycerol sebacate) Designed to Match the Mechanical Properties of Myocardial Tissue” Biomaterials 29(1):47-57.
[28] Jiang, W.C., Cheng Y. H., Yen, M.H., Chang, Y., Yang, V.W., Lee, K. (2014) “Cryo-Chemical Decellularization of the Whole Liver for Mesenchymal Stem Cells-Based Functional Hepatic Tissue Engineering.” Biomaterials 35(11):3607-3617.
[29] Melchels, F.P., Feijen, J., Grijpma, D.W. (2010) “A Review on Stereolithography and its Applications in Biomedical Engineering.” Biomaterials 34(24):6121-6130.
[30] Sakai, Y., Huang, H., S. Hanada, T. Niino. (2010) “Toward Engineering of Vascularized Three-Dimensional Liver Tissue Equivalents Possessing a Clinically Significant Mass.” Biochemical Enginerring Journal 48(3):348-361.
[31] Liu, T.V., Chen, A.A., Cho, L.M., Jadin, K.D., Sah, R.L., De, S.L., et al. (2007) “Fabrication of 3D Hepatic Tissues by Additive Photopatterning of Cellular Hydrogels.” FASEB J. 21:790-801.
[32] Li, X., He, J., Liu, Y., Zhao, Q., Wu, W., Li, D., et al. (2013) “Biomaterial Scaffolds with Biomimetic Fluidic Channels for Hepatocyte Culture.” Journal of Bionic Engineering:57-64.
[33] Woodrow K.A., Wood M.J., Saltzman W.M. (2009) “Biodegradable Meshes Printed with Extracellular Matrix Proteins Support Micropatterned Hepatocyte Cultures” Tissue Engineering Part A15(5):1169-1179.
[34] Zein I., Hutmacher D.W., Teoh S.H. (2002) “Fused Deposition Modeling of Novel Scaffold Architectures for Tissue Engineering Applications” Biomaterials 23(4):1169-1185
[35] Organovo: http://organovo.com/
[36] Cornelissen D.J., Faulkner-Jones, A., Shu, W. (2017) “Current Developments in 3D Bioprinting for Tissue Engineering.” Current Opinion in Biomedical Engineering 2:76-82.
[37] 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.
[38] 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.
[39] 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.
[40] 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.
[41] 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.
[42] 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.
[43] 杜睿恩，2016，“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.
[44] 洪睿廷，2016 “使用積層製造技術製作光固化Poly(ε-caprolactone)diacrylate/ Poly(ethylene glycol) 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.