近年肝組織工程技術為治療肝臟疾病的重要方法之一，但常遇到材料功能性不足等問題，因此仍有許多研發的需求。生物活性玻璃釋放的特定離子在肝組織修復中扮演著重要的角色，因此本研究添加生物活性玻璃於光固化生醫材料中以DLP型3D列印製程來製造肝臟支架，希望能夠提高細胞活性及增生功能，應用於肝組織工程。
主要材料系統為PGSA60+PEG-DA和PGSA60+PCL-DA，於其中添加1、5、7、10wt%之生物活性玻璃，首先透過材料混合探討將生物活性玻璃分散於光固化生醫材料中且靜置兩小時不會產生沉澱，接下來將混合好的材料去做列印，對列印後之樣品進行精度量測、拉伸試驗、降解試驗、親疏水性試驗、熱性質測試等性質檢測。發現楊氏模量和降解速率隨著生物活性玻璃添加量增加而提高，而伸長率、支架精度則會下降，其餘則無明顯影響。當添加10wt%時影響最大，楊氏模量上升58%、支架精度誤差則達到34.77%、伸長率下降37.4%，降解速率則上升了108.2%。最後針對添加1、5、7、10wt%生物活性玻璃進行細胞實驗，發現7wt%之添加量時細胞活性最佳，其中主材料系統中PGSA60+PCL-DA添加7wt%於第七天之細胞活性提昇42.6%，表現最佳。

In recent years, liver tissue engineering technology is one of the important methods for the treatment of liver diseases, but it often encounters problems such as insufficient material functionality, so there is still a lot of research and development needs. The specific ions released by bioactive glass(BG) play an important role in the repair of liver tissue. Therefore, this study adds BG to light-cured biomaterials to manufacture liver scaffolds using DLP 3D printing process, hoping to improve cell viability and Proliferation function, applied to liver tissue engineering.
The main materials systems are PGSA60+PEG-DA and PGSA60 +PCL-DA, in which 1, 5, 7,and 10wt% BG are added. Leave it for two hours without precipitation. Next, perform property test like tensile, degradation, accuracy measurement, hydrophilicity, and thermal property on the sample. It was found that the Young's modulus and degradation rate would increased with the addition of BG, while the elongation and stent accuracy would decrease, while the rest had no significant effect. The effect is greatest when 10wt% is added, the Young's modulus increases by 58%, the degradation rate increases by 108.2%, the accuracy error of the stent reaches 34.77%, and the elongation decreases by 37.4%. Finally, cell experiments were carried out with the addition of 1, 5, 7, and 10wt% BG, and the cell activity was the best when the addition amount of 7wt% was added. Among them, the main material system PGSA60+PCL-DA added 7wt% to the cell activity on the seventh day An increase of 42.6%.

【1】 L. L. Hench, “The story of Bioglass®,” Journal of Materials Science: Materials in Medicine 17 (11) ,967-978, 2006.
【2】 F. Baino, "Bioactive glasses – When glass science and technology meet regenerative medicine," Ceramics International 44(13), 14953-14966, 2018.
【3】 S. Kargozar, F. Baino, S. Hamzehlou, R. G. Hill and M. Mozafari, "Bioactive Glasses: sprouting angiogenesis in tissue engineering," Trends Biotechnol 36(4), 430-444, 2018.
【4】 T. Agarwal, T. K. Maiti, S. K. Ghosh, "Decellularized caprine liver- derived biomimetic and pro-angiogenic scaffolds for liver tissue engineering," Mater Sci Eng C 98, 939-948, 2019.
【5】 Y. Ikada “Challenges in tissue engineering.”J. R. Soc. Interface 3, 589-601, 2006
【6】 L. G. Griffith, G. Naughton, “Tissue engineering-current challenges and expanding oppurtunities.”Science 295, 8 , 2002
【7】 F. Akter, “Principles of tissue engineering”Tissue Engineering Made Easy, Academic Press, 3-16, 2016
【8】 宋信文 梁晃千，“建立人類的身體工房-組織工程”，科學發展第362期，2003年。
【9】 楊婷琪，“組織工程的重要元件-生物分子”，工研院經貿中心生醫組，2002年。
【10】 廖俊仁，“組織工程用多孔隙骨架材料”，工研院生醫工程中心，2002年
【11】 S.Yang , K. F.Leong, , Z. Du, and C.K Chua “The design of scaffolds for use in tissue engineering. Part I. Traditional factors.”Tissue Eng, 679-689, 2001
【12】 C. Becker, G. Jakse, “Stem cells for regeneration of urological structures.” Eur Urol, 51, 1217-28, 2007
【13】 M. P. Nikolova, M. S. Chavali, “Recent advances in biomaterials for 3D scaffolds: A review”Bioactive Materials, 4 ,271-292, 2019
【14】 S. Ullah, X. Chen, “Fabrication, applications and challenges of natural biomaterials in tissue engineering”Applied Materials Today, 20, 100656, 2020
【15】 R. Pugliese, B. Beltrami, S. Regondi, C. Lunetta, “Polymeric biomaterials for 3D printing in medicine: An overview”Annals of 3D printed Medicine ,2 ,100011, 2021
【16】 許芳豪，“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，2006年。
【17】 H. Kweon , M.K. Yoo , I.K. Park , T.H. Kim , H.C. Lee , H.S. Lee , J.S. Oh , T. Akaike , C.S. Cho , “A novel degradable polycaprolactone networks for tissue engineering ”Biomaterials ,24 ,801–808, 2003
【18】 蔡秉宏，”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，1999年。
【19】 D. S, “Medical application of synthetic polymers,” Marcel Dekker, 725, 1994
【20】 J. S. Park, D. G. Woo, B. K. Sun, “In vitro and in vivo test of PEG/PCL-based hydrogel scaffold for cell delivery application,” Journal of Controlled Release, 124, 51-59, 2007
【21】 J. Gao, P.Y. Crapo, M.D. Wang, “Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering”, Tissue Eng , 2006
【22】 J. Wang, K.G. Boutin, O. Abdulhadi, L.D. Personnat, T. Shazly, R. Langer, C.L. Channick, J.T. Borenstein, “Fully biodegradable airway stents using amino alcohol-basedPoly(ester amide) elastomers”, Advanced healthcare materials , 2013
【23】 Q. Z. Chen, A. Bismarck, U. Hansen, S. Junaid, M. Q.Tran,
S. E. Harding, N. N. Ali, A. R. Boccaccini, “Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the
mechanical properties of myocardial tissue” Biomaterials, 47-57, 2008
【24】 C. L. E. Nijst, J. P. Bruggeman, J. M. Karp, L. Ferreira, A.
Zumbuehl, C. J. Bettinger, R. Langer,''Synthesis and characterization of photocurable elastomers from poly(glycerol-co-sebacate)'',Biomacromolecules 3067-3073, 2007
【25】 J. Y. Chen, J. V. Hwang, W. S. Ao-leng, Y. C. Lin, Y. K. Hsieh, Y. L. Cheng, J. Wang, “Study of physical and degradation properties of 3D-printed biodegradable, photocurable copolymers, PGSA-co-PEGDA and PGSA-co-PCL-DA”Polymers 10, 1263, 2018
【26】 C. L. Teng, J. Y. Chen, T. L. Chang, S. K. Hsiao, Y. K. Hsieh, K. V. Gorday, Y. L. Cheng and J. Wang.“Design of photocurable, biodegradable scaffolds for liver lobule regeneration via digital light process-additive manufacturing” Biofabrication, 123, 2020
【27】 M. Vallet-Regí, “Nanostructured mesoporous silica matrices in nanomedicine,” Journal of Internal Medicine, 267(1), 22-43, 2010.
【28】 P. Valerio, M. M. Pereira, A. M. Goes, M.F. Leite, “The effect of ionic products from bioactive glass dissolution on osteoblast proliferation and collagen production,” Biomaterials, 25(15), 2941-2948, 2004.
【29】 J. R. Jones, “Reprint of: review of bioactive glass: from Hench to hybrids” Acta Biomaterialia, 23, S53-S82, 2015
【30】 S. Kargozer, M. Mozafari, S. Hamzehlou, F. Baino. “Using bioactive glasses in the management of burns” Frontiers in Bioengineering and Biotechnology, 7, 62, 2019
【31】 M.W. Davis, J.P. Vacanti. “Toward development of an
implantable tissue-engineered liver.” Biomaterials, 365-
372, 1996
【32】 J.W. Allen, S.N. Bhatia. “Engineering liver therapies for the
future.”Tissue Eng, 725 -737, 2002
【33】 M. H. Zheng, C. Ye, M. Braddock, Y. P. Chen, “Liver tissue
engineering: promises and prospects of new technology.” Cytotherapy, 349-360, 2010
【34】 胡泉，李穎，周瑾，王常勇，“肝組織工程的研究進展與展望”，2011年。
【35】 T. Saadi, et al., “Cellularized biosynthetic microhydrogel
polymersfor intravascular liver tissue regeneration therapy.” Tissue Eng, 20(21-22), 2014
【36】 J. Kasuya, et al., “Reconstruction of 3D stacked hepatocyte
tissuesusing degradable, microporous poly (d,l-lactide-co-glycolide)membranes. ” 33(9), 2693-2700, 2012
【37】 E. A. Vogler, “Structure and reactivity of water at biomaterial surfaces.” Advances in Colloid and Interface Science, 74(1–3), 69-117, 1998
【38】 H.C. Fiegel, et al., “Hepatic tissue engineering: from
transplantation to customized cell-based liver directed therapies
from thelaboratory.”J Cell Mol Med, 12(1), 56-66, 2008
【39】 M. Bockhorn, et al., “VEGF is important for early liver
regeneration after partial hepatectomy.” J Surg Res, 138(2), 2007
【40】 K.M. Kulig, J. P. Vacanti, “Hepatic tissue engineering.” Transpalnt Immunology 12(3), 303-310, 2004
【41】 A. Baqureizo, R. Banares, F. Saliba, “Current linicla status of the extracorporeal liver support devices.” W. B. Saunders, 1463-1487, 2015
【42】 O. Barakat, S. Abbasi, G. Rodriguez, J. Rios, R. P. Wood, C. Ozaki, L. S. Holley, P. K. Gauthier, “Use of decellularized porcine liver for engineering humanized liver organ.” Journal of Surgical Research, 73, e11-e25, 2012
【43】 W. C. Jiang, Y. H. Cheng, M. H. Yen, Y. Chang, V. W. Yang, K. Lee . “Cryo-chemical decellularization of the whole liver for
mesenchymal stem cells-based functional hepatic tissue engineering.” Biomaterials, 35(11), 3607-3617, 2014
【44】 C. Yua, X. Mab , W. Zhua , P. Wangc , K. L. Millera , J. Stupind , A. Koroleva-Maharajhd , A. Hairabediand , S. Chena, “Scanningless and continuous 3D bioprinting of human tissues with decellularized extracellular matrix.” Biomaterials, 194, 1-13, 2019
【45】 F. P. Melchels, J. Feijen, D. W. Grijpma. “A review on
stereolithography and its applications in biomedical engineering.” Biomaterials, 31(24), 6121-6130, 2010

【46】 Y. Sakai, H. Huang, S. Hanada, T. Niino. “Toward engineering of vascularized three-dimensional liver tissue equivalents possessing a clinically significant mass.” Biochemical Engineer Journal, 48(3), 348-361, 2010
【47】 T. V. Liu, A. A. Chen, L. M. Cho, K. D. Jadin, R. L. Sah, S. L. De, et al. “Fabrication of 3D hepatic tissues by additive
photopatterning of cellular hydrogels.” FASEB J, 21(3), 790-80, 2006.
【48】 X. Li, J. He, Y. Liu, Q. Zhao, W. Wu, D. Li, et al “Biomaterial
scaffolds with biomimetic fluidic channels for hepatocyte
culture.” Journal of Bionic Engineering, 10, 57-64, 2013.
【49】 K. A. Woodrow, M. J. Wood, W. M. Saltzman, “Biodegradable meshes printed with extracellular matrix proteins support micropatterned hepatocyte cultures.” Tissue Engineer A, 15(5), 1169–1179, 2008
【50】 I. Zein, D. W. Hutmacher, S. H. Teoh, “Fused deposition modeling of novel scaffold architectures for tissue engineering
applications.” Biomaterials, 20(4), 1169–1185, 2002
【51】 Organovo: http://organovo.com/
【52】 D. J. Cornelissen, A. Faulkner-Jones, W. Shu,“Current developments in 3D bioprinting for tissue engineering.” Current Opinion in Biomedical Engineering, 2, 76-82, 2017
【53】 Z. Liu, Y. Li, Wei Li, C. Xiao, D. Liu, C. Dong, M. Zhang, E. Mäkilä, M. Kemell, J. Salonen, J. T. Hirvonen, H. Zhang, D. Zhou, X. Deng, and H. A. Santos. “Multifunctional nanohybrid based on porous silicon nanoparticles, gold nanoparticles, and acetalated dextran for liver regeneration and acute liver failure theranostics.” Advanced Materials, 30(24), 2017
【54】 J. A. Santos-López, A. Garcimartín, P. Merino, M. E. López-Oliva, S. Bastida, J. Benedí, F. J. Sánchez-Muniz,“Effects of silicon vs. hydroxytyrosol-enriched restructured pork on liver oxidation status of aged rats fed high-saturated/high cholesterol diets.” PLoS ONE, 11(1), 2016
【55】 C. D. Seaborn, F. H. Nielsen,“Silicon deprivation decreases collagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver.” Biol Trace Elem Res, 89, 251–261, 2002
【56】 M. J. Amaya, M. H. Nathanson,“Calcium signaling in the liver.” Compr Physiol, 3(1), 515–539, 2013
【57】 S. H. Hong, J. A. Kwak, J. Y. Jeon, C. S. Park,“Prediction of early allograft dysfunction using serum phosphorus level in living donor liver transplantation.” Transpl Int, 26, 402-410, 2013
【58】 Baquerizo, Angeles, Anselmo, Dean, Shackleton, Christopher,Chen, Teng-Wei, Cao, Carlos,Weaver, Michael, Gornbein, Jeffrey, Geevarghese, Sunil, Nissen, Nicholas, Farmer, Douglas,Demetriou, Achilles, Busuttil, Ronald W.“Phosphorus ans an early predictive factor in patients with acute liver failure1.” Transplantation, 75(12), 2007-2014, 2003
【59】 H. Khaliq, Z. Juming, P. Ke-Mei, “The Physiological Role of Boron on Health.” Biol Trace Elem Res 186, 31–51, 2018.
【60】 楊淯凱，“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，2013年。
【61】 許淯維，“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，2016年。
【62】 杜睿恩，“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，2017年。
【63】 吳沛頡，“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，2018年。
【64】 王潔、鄭逸琳、陳怡文、謝明佑，可積層製造的生物可降解光聚合高分子複合材料及其應用。US 10377865、
TW I644801
【65】 許家寧，“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.”，國立台灣科技大學機械工程研究所，碩士論文，2020年。
【66】 PL Industries
http://products.plindustries.esstechinc.com/item/free-radical-photoinitiators/pl-tpo-free-radical-photoinitiators/pl-tpo
【67】 J. P. Schneider, L. Pedersen, C. Muhlfeld, M. Ochs. “Staining
histological lung sections with Sudan Black B or Sudan III for automated identification of alveolar epithelial type II cells.” Acta histochemica, 117, 675-680, 2015
【68】 Sigma-Aldrich http://www.sigmaaldrich.com/catalog/substance/sudanblackb45654419725511?lang=en®ion=TW&attrlist=Brand
【69】 翁于倫，“DLP 3D列印多孔陶瓷及其於 微過濾與SOFC陽極之應用”，國立台灣科技大學機械工程研究所，碩士論文，2020年。
【70】 鄧佳琳，“運用可3D列印之可吸收生物材料促進肝細胞再生”，國立清華大學化學工程系，碩士論文，2017年。
【71】 L. Ji, W. Wang, D. Jin, S. Zhou, X. Song, “In vitro bioactivity and mechanical properties of bioactive glass nanoparticles/polycaprolactone composites Materials.” Science and Engineering: C, 46, 1-9, 2015