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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 高分子科學與工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/97868
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dc.contributor.advisor徐善慧zh_TW
dc.contributor.advisorShan-hui Hsuen
dc.contributor.author張永辰zh_TW
dc.contributor.authorYung-Chen Changen
dc.date.accessioned2025-07-18T16:12:59Z-
dc.date.available2025-07-19-
dc.date.copyright2025-07-18-
dc.date.issued2025-
dc.date.submitted2025-07-17-
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(11) Lee, J. B.; Wang, X.; Faley, S.; Baer, B.; Balikov, D. A.; Sung, H.-J.; Bellan, L. M. Development of 3D microvascular networks within gelatin hydrogels using thermoresponsive sacrificial microfibers. Adv. Healthcare Mater. 2016, 5 (7), 781-785.
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(14) Tseng, T.-C.; Hsieh, F.-Y.; Theato, P.; Wei, Y.; Hsu, S.-h. Glucose-sensitive self-healing hydrogel as sacrificial materials to fabricate vascularized constructs. Biomaterials 2017, 133, 20-28.
(15) Cheng, K.-C.; Theato, P.; Hsu, S.-h. 3D-bioprintable endothelial cell-laden sacrificial ink for fabrication of microvessel networks. Biofabrication 2023, 15 (4), 045026.
(16) Mohanty, S.; Borah, K.; Kashyap, S. S.; Sarmah, S.; Bera, M. K.; Basak, P.; Narayan, R. Development of hydrophobic polyurethane film from structurally modified castor oil and its anticorrosive performance. Polym. Adv. Technol. 2023, 34 (1), 351-362.
(17) Peng, S.; Thirunavukkarasu, N.; Chen, J.; Zheng, X.; Long, C.; Huang, X.; Weng, Z.; Zheng, L.; Wang, H.; Peng, X. Vat photopolymerization 3D printing of transparent, mechanically robust, and self-healing polyurethane elastomers for tailored wearable sensors. Chem. Eng. J. 2023, 463, 142312.
(18) Yu, Z.; Sun, X.; Zhu, Y.; Zhou, E.; Cheng, C.; Zhu, J.; Yang, P.; Zheng, D.; Zhang, Y.; Panahi-Sarmad, M.; Jiang, F. Direct ink writing 3D printing elastomeric polyurethane aided by cellulose nanofibrils. ACS Nano 2024, 18 (41), 28142-28153.
(19) Hsu, S.-h.; Dai, L. G.; Hung, Y. M.; Dai, N. T. Evaluation and characterization of waterborne biodegradable polyurethane films for the prevention of tendon postoperative adhesion. Int. J. Nanomed. 2018, 13, 5485-5497.
(20) Chen, Y.-P.; Hsu, S.-h. Preparation and characterization of novel water-based biodegradable polyurethane nanoparticles encapsulating superparamagnetic iron oxide and hydrophobic drugs. J. Mater. Chem. B 2014, 2 (21), 3391-3401.
(21) Ou, C.-W.; Su, C.-H.; Jeng, U. S.; Hsu, S.-h. Characterization of biodegradable polyurethane nanoparticles and thermally induced self-assembly in water dispersion. ACS Appl. Mater. Interfaces 2014, 6 (8), 5685-5694.
(22) Hsu, S.-h.; Hsieh, C.-T.; Sun, Y.-M. Synthesis and characterization of waterborne polyurethane containing poly(3-hydroxybutyrate) as new biodegradable elastomers. J. Mater. Chem. B 2015, 3 (47), 9089-9097.
(23) Hsieh, F.-Y.; Lin, H.-H.; Hsu, S.-h. 3D bioprinting of neural stem cell-laden thermoresponsive biodegradable polyurethane hydrogel and potential in central nervous system repair. Biomaterials 2015, 71, 48-57.
(24) Huang, C.-T.; Kumar Shrestha, L.; Ariga, K.; Hsu, S.-h. A graphene–polyurethane composite hydrogel as a potential bioink for 3D bioprinting and differentiation of neural stem cells. J. Mater. Chem. B 2017, 5 (44), 8854-8864.
(25) Hsieh, C.-T.; Hsu, S.-h. Double-network polyurethane-gelatin hydrogel with tunable modulus for high-resolution 3D bioprinting. ACS Appl. Mater. Interfaces 2019, 11 (36), 32746-32757.
(26) Cheng, K.-C.; Sun, Y.-M.; Hsu, S.-h. Development of double network polyurethane–chitosan composite bioinks for soft neural tissue engineering. J. Mater. Chem. B 2023, 11 (16), 3592-3606.
(27) Gaharwar, A. K.; Rivera, C. P.; Wu, C.-J.; Schmidt, G. Transparent, elastomeric and tough hydrogels from poly (ethylene glycol) and silicate nanoparticles. Acta Biomater. 2011, 7 (12), 4139-4148.
(28) Anspach, A.; Bider, F.; Völkl, A. R.; Klupp Taylor, R. N.; Boccaccini, A. R. Incorporating silica nanoparticles with silver patches into alginate-based bioinks for 3D bioprinting. MRS Commun. 2024, 14 (6), 1460-1466.
(29) Özcan, M.; Kaya, C.; Kaya, F. Cosmic radiation shielding property of boron reinforced continuous fiber nanocomposites produced by electrospinning. Discover Nano 2023, 18 (1), 152.
(30) Nasiripour, S.; Pishbin, F.; Seyyed Ebrahimi, S. 3D printing of a self-healing, bioactive, and dual-cross-linked polysaccharide-based composite hydrogel as a scaffold for bone tissue engineering. ACS Appl. Bio Mater. 2025, 8 (1), 582-599.
(31) Roh, H.-H.; Kim, H.-S.; Kim, C.; Lee, K.-Y. 3D printing of polysaccharide-based self-healing hydrogel reinforced with alginate for secondary cross-linking. Biomedicines 2021, 9 (9), 1224.
(32) Lokhande, G.; Carrow, J. K.; Thakur, T.; Xavier, J. R.; Parani, M.; Bayless, K. J.; Gaharwar, A. K. Nanoengineered injectable hydrogels for wound healing application. Acta Biomater. 2018, 70, 35-47.
(33) Yang, J.; Zhao, J.-J.; Han, C.-R.; Duan, J.-F. Keys to enhancing mechanical properties of silica nanoparticle composites hydrogels: The role of network structure and interfacial interactions. Compos. Sci. Technol. 2014, 95, 1-7.
(34) Aung, Y.-Y.; Kristanti, A. N.; Lee, H. V.; Fahmi, M. Z. Boronic-acid-modified nanomaterials for biomedical applications. ACS Omega 2021, 6 (28), 17750-17765.
(35) Zhang, L.; Lin, Y.; Wang, J.; Yao, W.; Wu, W.; Jiang, X. A facile strategy for constructing boron‐rich polymer nanoparticles via a boronic acid‐related reaction. Macromol. Rapid Commun. 2011, 32 (6), 534-539.
(36) Yeo, J. C. C.; Muiruri, J. K.; Thitsartarn, W.; Li, Z.; He, C. Recent advances in the development of biodegradable PHB-based toughening materials: Approaches, advantages and applications. Mater. Sci. Eng. C 2018, 92, 1092-1116.
(37) Lin, K.-W.; Lan, C.-H.; Sun, Y.-M. Poly[(R)3-hydroxybutyrate] (PHB)/poly(L-lactic acid) (PLLA) blends with poly(PHB/PLLA urethane) as a compatibilizer. Polym. Degrad. Stab. 2016, 134, 30-40.
(38) Cheng, M.-L.; Lin, C.-C.; Su, H.-L.; Chen, P.-Y.; Sun, Y.-M. Processing and characterization of electrospun poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) nanofibrous membranes. Polymer 2008, 49 (2), 546-553.
(39) Zhu, Z.; Xie, C.; Liu, Q.; Zhen, X.; Zheng, X.; Wu, W.; Li, R.; Ding, Y.; Jiang, X.; Liu, B. The effect of hydrophilic chain length and iRGD on drug delivery from poly(ε-caprolactone)-poly(N-vinylpyrrolidone) nanoparticles. Biomaterials 2011, 32 (35), 9525-9535.
(40) Schärtl, W. Light Scattering from Polymer Solutions and Nanoparticle Dispersions; Springer, 2007
(41) Ho, L.; Hsu, S.-h. Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs. Acta Biomater. 2018, 70, 57-70.
(42) Chen, T.-C.; Wong, C.-W.; Hsu, S.-h. Three-dimensional printing of chitosan cryogel as injectable and shape recoverable scaffolds. Carbohydr. Polym. 2022, 285, 119228.
(43) Herrada-Manchón, H.; Fernández, M. A.; Aguilar, E. Essential guide to hydrogel rheology in extrusion 3D printing: How to measure it and why it matters? Gels 2023, 9 (7), 517.
(44) Zhang, X.; Waymouth, R. M. 1,2-Dithiolane-derived dynamic, covalent materials: Cooperative self-assembly and reversible cross-linking. J. Am. Chem. Soc. 2017, 139 (10), 3822-3833.
(45) Zheng, N.; Xu, Y.; Zhao, Q.; Xie, T. Dynamic covalent polymer networks: A molecular platform for designing functions beyond chemical recycling and self-healing. Chem. Rev. 2021, 121 (3), 1716-1745.
(46) Rastin, H.; Zhang, B.; Bi, J.; Hassan, K.; Tung, T. T.; Losic, D. 3D printing of cell-laden electroconductive bioinks for tissue engineering applications. J. Mater. Chem. B 2020, 8 (27), 5862-5876.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/97868-
dc.description.abstract添加奈米粒子可提升水凝膠的3D列印性,然而,軟性且可變形奈米粒子於水凝膠網絡中對3D列印影響仍未被深入探討。本研究合成兩種具硼酸官能基之聚胺酯奈米粒子(PUB與PUB')作為動態奈米交聯劑以構建可3D生物列印的水凝膠,其中,PUB 的軟鏈段僅由poly(ε-caprolactone) (PCL) 組成,而PUB'則由PCL、poly(D,L-lactide)及poly(3-hydroxybutyrate)依0.7/0.2/0.1莫耳比例組成。透過小角度X光散射分析顯示,PUB奈米粒子呈現球形結構,PUB'則為偏橢球形結構。基於動態點擊交聯化學所製備poly(ethylene glycol)水凝膠中,PUB'-交聯水凝膠表現出更高之剪切模量與蠕變抗性,且經由160 μm小口徑噴頭列印時PUB'-交聯水凝膠展現出優異的堆疊性與線條解析度。由時間解析SAXS分析進一步揭示PUB'奈米粒子於凝膠化過程中會延展並穩定維持橢球形態,該現象使水凝膠內部形成高達38%奈米粒子體積分率進而提升其列印堆疊性;相對地,PUB奈米粒子則由球形結構轉為扁平狀結構導致水凝膠內部奈米粒子體積分率僅18%。此外,兩種水凝膠皆可維持高達約92%的內皮細胞活性。綜上所述,本研究揭示了聚胺酯-硼酸奈米交聯劑於凝膠化過程中的形貌轉變機制及其對內部奈米粒子體積分率高低與3D列印堆疊性的影響,並進一步說明了軟性奈米粒子形貌在動態自癒合水凝膠與3D列印墨水設計上的關鍵角色。zh_TW
dc.description.abstractAddition of nanoparticles in a hydrogel can enhance its three-dimensional (3D) printability. However, the role of soft, deformable nanoparticles in the 3D printability of a hydrogel network has not been explored so far. In this study, two boronic acid-functionalized polyurethane nanoparticles PUB and PUB' are synthesized as soft dynamic nano-crosslinker to construct 3D bioprintable hydrogel. The soft segment of PUB consists of poly(ε-caprolactone) (PCL) solely while that of PUB' consists of PCL, poly(D,L-lactide), and poly(3-hydroxybutyrate) in 0.7/0.2/0.1 molar ratio. Coherent small-angle X-ray scattering (SAXS) reveals that PUB nanoparticles are nearly spherical while PUB' nanoparticles are ellipsoidal. PUB'-crosslinked poly(ethylene glycol) hydrogel based on dynamic click chemistry has greater shear modulus and creep resistance than PUB-crosslinked hydrogel. When printed through a small (160 μm) nozzle, PUB'-based hydrogel exhibits superior stackability and filament resolution. Time-resolved SAXS analysis unveils that PUB' nanoparticles elongate and maintain a stable ellipsoidal morphology in the network during gelation, contributing to higher packing density (particle volume fraction 38%) and 3D stackability of the hydrogel. Meanwhile, PUB nanoparticles transform from spherical to ellipsoidal and are eventually flattened, leading to low packing density (particle volume fraction 18%) of the hydrogel. Moreover, endothelial cells laden in both hydrogels show high vitality (~92%). The unique shape deformation phenomenon of the polyurethane-boronic acid nano-crosslinker during gelation and the resulted high-density packing in the dynamic network provide insights into the role of soft nanoparticle morphology in the stackability of a dynamic self-healing hydrogel and the role of particle packing in designing 3D hydrogel inks.en
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dc.description.provenanceMade available in DSpace on 2025-07-18T16:12:59Z (GMT). No. of bitstreams: 0en
dc.description.tableofcontents致謝 I
中文摘要 II
英文摘要 III
目次 V
圖次 VII
表次 VIII
第一章 文獻回顧 1
1.1. 水凝膠概述 1
1.2. 犧牲性水凝膠及其在組織工程中的應用 1
1.3. 聚胺酯生物墨水研究與開發 2
1.4. 研究背景與動機 3
第二章 研究方法 5
2.1. 水性可降解硼酸官能基聚胺酯(PUB和PUB')合成 5
2.2. 葡萄糖敏感型水凝膠之製備 9
2.3. PDUB與PDUB'水凝膠的流變學及蠕變測試 9
2.4. 小角X光散射(SAXS)與穿透式電子顯微鏡(TEM)結構與形貌分析 10
2.5. PDUB2和PDUB2'水凝膠的自癒合速率及3D列印性 12
2.6. PDUB和PDUB'水凝膠的細胞培養與細胞相容性 13
2.7. PDUB2和PDUB2'水凝膠的葡萄糖敏感性 13
2.8. 利用PDUB2'水凝膠作為犧牲模板製備帶有中空微通道的構建體 14
2.9. 統計分析 14
第三章 實驗結果 15
3.1. 水性可生物降解硼酸功能化聚胺酯(PUB與PUB')之合成 15
3.2. PDUB與PDUB'水凝膠的製備 19
3.3. PDUB及PDUB'水凝膠之流變性質 23
3.4. 以SAXS及TEM分析PDUB2與PDUB2'水凝膠形成過程中的時間解析結構變化 29
3.5. PDUB和PDUB'水凝膠的自癒合速率與時間依賴性蠕變行為 35
3.6. 細胞相容性 36
3.7. PDUB與PDUB'水凝膠的葡萄糖敏感性堆疊性及列印解析度 37
第四章 討論 42
第五章 結論 46
參考資料 47
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dc.language.isozh_TW-
dc.subject奈米粒子zh_TW
dc.subject小角度X光散射zh_TW
dc.subject聚胺酯zh_TW
dc.subject葡萄糖敏感性水凝膠zh_TW
dc.subject奈米粒子zh_TW
dc.subject3D列印zh_TW
dc.subject小角度X光散射zh_TW
dc.subject聚胺酯zh_TW
dc.subject葡萄糖敏感性水凝膠zh_TW
dc.subject3D列印zh_TW
dc.subjectSAXSen
dc.subject3D printingen
dc.subjectnanoparticlesen
dc.subjectglucose-sensitive hydrogelen
dc.subjectpolyurethaneen
dc.subjectSAXSen
dc.subject3D printingen
dc.subjectnanoparticlesen
dc.subjectglucose-sensitive hydrogelen
dc.subjectpolyurethaneen
dc.title軟性可變形硼酸官能基化聚胺酯奈米粒子作為動態交聯劑應用於水凝膠之3D生物列印zh_TW
dc.titleSoft, Deformable Polyurethane-Boronic Acid Nanoparticles as Dynamic Cross-Linkers to Construct 3D-Bioprintable Hydrogelsen
dc.typeThesis-
dc.date.schoolyear113-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee孫一明;賴育英zh_TW
dc.contributor.oralexamcommitteeYi-Ming Sun;Yu-Ying Laien
dc.subject.keyword3D列印,奈米粒子,葡萄糖敏感性水凝膠,聚胺酯,小角度X光散射,zh_TW
dc.subject.keyword3D printing,nanoparticles,glucose-sensitive hydrogel,polyurethane,SAXS,en
dc.relation.page52-
dc.identifier.doi10.6342/NTU202501909-
dc.rights.note同意授權(限校園內公開)-
dc.date.accepted2025-07-18-
dc.contributor.author-college工學院-
dc.contributor.author-dept高分子科學與工程學研究所-
dc.date.embargo-lift2025-07-19-
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