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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林致廷 | zh_TW |
| dc.contributor.advisor | Chih-Ting Lin | en |
| dc.contributor.author | 施凡妮 | zh_TW |
| dc.contributor.author | Subhashree Shivani | en |
| dc.date.accessioned | 2026-01-27T16:20:32Z | - |
| dc.date.available | 2026-01-28 | - |
| dc.date.copyright | 2026-01-27 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2026-01-20 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101376 | - |
| dc.description.abstract | 目前體外血管模型主要基於微壓印、人工血管或自組裝微血管為主。然而因主要技術是使用靜脈內皮細胞或其他多能幹細胞轉化的內皮細胞，所培養出的血管以微血管為主。然而，動脈在調節血管張力和疾病進展中是為主要血管組織，但如何在體外重建其多層細胞結構和血液動力學環境仍然是此領域的重大挑戰。在本研究中，我們開發了一種微流控平台，能夠共培養人類動脈內皮細胞、平滑肌細胞（SMC）和纖維母細胞，誘使其產生自組裝病培養出具有功能性的小動脈組織。本研究藉由在經片中產生低氧條件下，誘導血管生成和並將其發展成穩定且成熟的小動脈組織，並證明週期性血流會使其產生動態重塑機制。本研究透過改變剪應力，我們證實了小動脈的血流依賴性的血管重塑機制，以實驗證明在靜態培養下會喪失血管功能，在低剪應力下會誘導擴張性重塑，而高剪應力則會觸發擴張和退化性重塑，最終形成具有小動脈層狀結構的功能性血管。本研究並以有限元素分析進一步分析出剪應力與初級和次級血管發育之間的關聯。本研究亦驗證平滑肌細胞具有血管收縮及舒張之小動脈功能，並證明此小動脈模型能夠重現早期動脈粥狀硬化的疾病模型。綜合以上所述，本研究所開發的小動脈晶片能夠重現人類小動脈的關鍵組織結構、功能和病理特徵。此平台將可做為研究動脈生成、內皮層及平滑肌細胞相互作用和血管疾病的一項體外工具，並有望應用於未來的藥物測試和個人化醫療 | zh_TW |
| dc.description.abstract | Current in vitro vessel models are primarily based on micro-patterning, artificial vessels, or self-assembled microvascular networks. However, most studies have used venous endothelial cells (ECs) or other pluripotent-derived ECs, resulting in the formation of capillary-like vessels. Arteries play a central role in regulating vascular tone and disease progression; however, recreating their multicellular structure and hemodynamic environment in vitro remains a major challenge. In this study, we developed a microfluidic platform capable of co-culturing primary human arterial endothelial cells, smooth muscle cells (SMC), and fibroblasts to generate self-assembled, perfused, and functional arteriole-like networks. Guided by vasculogenesis and angiogenesis under controlled hypoxia, the vascular structures matured into stable arterioles that responded o oscillatory flow. By varying shear stresses, we demonstrated flow-dependent vascular remodeling: static cultures showed loss of perfusion, low shear induced expansive remodeling, and high shear triggered both expansive and regressive remodeling, resulting in perfused vessels with an arteriole-layered anatomical structure. Finite element analysis further revealed the association between the magnitude and distribution of shear stress and the development of primary and secondary vessel hierarchies. Arteriole functionality was validated by SMC-mediated vasomotion, demonstrating the model’s ability to recapitulate early atherosclerotic events. Together, these results establish a physiologically relevant arteriole model that recapitulates key human arteriole features and enables studies of arteriogenesis, endothelial–SMC interactions, vascular disease, and drug testing. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2026-01-27T16:20:32Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2026-01-27T16:20:32Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Acknowledgements i
中文摘要 iii Abstract iv Contents v List of Abbreviations viii 1. Introduction 1 1.1 Significance 1 1.2 Research Aims 3 1.2.1 Development of perfusable arteriole-on-a-chip 3 1.2.2 Verifying arteriolar functionality 4 1.2.3 Arterial disease modeling 5 1.3 Dissertation Structure 7 2. Background 9 2.1 Cardiovascular Network 9 2.2 Methods of vessel formation 10 2.2.1 Vasculogenesis 10 2.2.2 Angiogenesis 12 2.2.3 Arteriogenesis 13 2.3 Intravascular flow 14 2.4 Interstitial Flow 16 2.5 In vitro Models for Developing Vessel-on-a-chip 17 2.5.1 Patterned microchannel 18 2.5.2 Sacrificial molds 21 2.5.3 Self-Assembly 24 2.5.4 In vitro arterial models 27 2.5.5 Vascular disease models on a chip 30 2.6 Study of flow and arteriogenesis on a chip 34 3. Design Concept of Microfluidic Devices 39 3.1 Design Principles for developing Arteriole-on-a-chip devices 39 3.1.1 Microfluidic design principle concepts 39 3.1.2 Designing arteriole-on-a-chip device 46 3.1.3 Designing set up for diffusion based mass transfer in the arteriole device 50 3.1.4 Designing set up for convection based mass transfer at high oscillating flow 53 3.1.5 Designing set up for convection based mass transfer at low oscillating flow 55 3.2 Experiment protocol for developing arteriole-on-a-chip 57 3.2.1 Overview of experiment timeline 57 3.2.2 Detailed workflow for developing arteriole-on-a-chip 58 4. Materials and Methods 62 4.1 Fabrication of Devices 62 4.1.1 Soft lithography technique for chip fabrication 62 4.2 Cell Culture and Immunostaining Methodologies 66 4.2.1 Cell culture 66 4.2.2 Cell Fixation 66 4.2.3 Immunohistochemistry Protocol 67 4.3 Whole blood acquisition 68 4.4 Quantification and Analysis 68 4.5 Finite Element Analysis 69 4.5.1 Obtaining 3D surface renderings of the vascular/basement network 69 4.5.2 Obtaining Finite Element Analysis 69 5. Results 71 5.1 Optimizing experimental protocol 71 5.1.1 Optimizing thrombin concentration 71 5.1.2 Optimizing fibronectin coating of side channel 73 5.2 Developing arteriole-on-a-chip 77 5.2.1 Vasculogenesis and angiogenesis for developing primary plexus 77 5.2.2 Arteriogenesis for vascular network remodeling and optimization 80 5.3 Effect of oscillating shear stress on vascular perfusability and dynamic remodeling 82 5.4 Analyzing arteriole network in response to different shear stress condition 87 5.5 Analyzing vascular network remodeling from initial vascular plexus using vessels and basement membrane 94 5.6 Finite element analysis of shear stress inside MVN 96 5.7 Vascular Functionality 100 5.7.1 Vasomotion in response to different dosage of dopamine 100 5.7.2 Nitric Oxide (NO) release in response to high shear stress 105 5.8 Arterial Disease Modeling 107 5.8.1 Thrombosis 107 5.8.2 Atherosclerosis 111 6. Discussion 114 7. Conclusion 122 8. Future Work 123 9. References 124 10. Appendix 147 10.1 Certificate for reproduction of material from Lab on a Chip 147 10.2 Fluorescent Images 148 10.2.1 Fluorescent image for figures 5.12 and 5.15 148 10.2.2 Fluorescent images for figure 5.22 149 10.2.3 Fluorescent images for figure 5.24 and 5.25 149 | - |
| dc.language.iso | en | - |
| dc.subject | 小動脈晶片 | - |
| dc.subject | 微流體晶片 | - |
| dc.subject | 血管重塑 | - |
| dc.subject | 血管舒縮 | - |
| dc.subject | 動脈粥樣硬化 | - |
| dc.subject | 器官晶片 | - |
| dc.subject | 微生理系統 | - |
| dc.subject | Arteriole-chip | - |
| dc.subject | Microfluidics | - |
| dc.subject | Vascular remodeling | - |
| dc.subject | Vasomotion | - |
| dc.subject | Atherosclerosis | - |
| dc.subject | Organ-on-a-Chip | - |
| dc.subject | Micrphysiological system | - |
| dc.title | 自組裝人類小動脈晶片及其在動脈功能檢測及疾病模型之應用 | zh_TW |
| dc.title | Self-assembled Human Arteriole-on-a-Chip for Arterial Functionality Testing and Disease Modelling | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.coadvisor | 許聿翔 | zh_TW |
| dc.contributor.coadvisor | Yu-Hsiang Hsu | en |
| dc.contributor.oralexamcommittee | 黃念祖;楊東霖;董奕鍾;張敬邦 | zh_TW |
| dc.contributor.oralexamcommittee | Nien-Tsu Huang;Tony Yang;Yi-Chung Tung;Ching-Pang Chang | en |
| dc.subject.keyword | 小動脈晶片,微流體晶片血管重塑血管舒縮動脈粥樣硬化器官晶片微生理系統 | zh_TW |
| dc.subject.keyword | Arteriole-chip,MicrofluidicsVascular remodelingVasomotionAtherosclerosisOrgan-on-a-ChipMicrphysiological system | en |
| dc.relation.page | 149 | - |
| dc.identifier.doi | 10.6342/NTU202600103 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2026-01-21 | - |
| dc.contributor.author-college | 電機資訊學院 | - |
| dc.contributor.author-dept | 生醫電子與資訊學研究所 | - |
| dc.date.embargo-lift | 2026-01-28 | - |
| 顯示於系所單位： | 生醫電子與資訊學研究所 | |
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| ntu-114-1.pdf | 10.28 MB | Adobe PDF | 檢視/開啟 |
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