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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 醫學工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/98103
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dc.contributor.advisor王兆麟zh_TW
dc.contributor.advisorJaw-Lin Wangen
dc.contributor.author陳冠蓁zh_TW
dc.contributor.authorGuan-Jen Chenen
dc.date.accessioned2025-07-25T16:05:19Z-
dc.date.available2025-07-26-
dc.date.copyright2025-07-25-
dc.date.issued2025-
dc.date.submitted2025-07-15-
dc.identifier.citation1. Hoy, D., et al., A systematic review of the global prevalence of low back pain. Arthritis & Rheumatism, 2012. 64(6): p. 2028-2037.
2. Hestbaek, L., C. Leboeuf-Yde, and K.O. Kyvik, Is comorbidity in adolescence a predictor for adult low back pain? A prospective study of a young population. BMC Musculoskeletal Disorders, 2006. 7(1): p. 29.
3. Dagenais, S., J. Caro, and S. Haldeman, A systematic review of low back pain cost of illness studies in the United States and internationally. The Spine Journal, 2008. 8(1): p. 8-20.
4. Schwarzer, A.C., et al., The Prevalence and Clinical Features of Internal Disc Disruption in Patients With Chronic Low Back Pain. Spine, 1995. 20(17).
5. Cassinelli, E.H. and J.D. Kang, Current understanding of lumbar disc degeneration. Operative Techniques in Orthopaedics, 2000. 10(4): p. 254-262.
6. Buckwalter, J.A., Spine update: Aging and degeneration of the human intervertebral disc. Spine, 1995. 20(11): p. 1307-1314.
7. Maroudas, A., et al., Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. Journal of Anatomy, 1975. 120(1): p. 113-130.
8. Whatley, B.R. and X. Wen, Intervertebral disc (IVD): Structure, degeneration, repair and regeneration. Materials Science and Engineering: C, 2012. 32(2): p. 61-77.
9. Le Maitre, C.L., A.J. Freemont, and J.A. Hoyland, Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Research & Therapy, 2007. 9(3): p. R45.
10. Roberts, S., et al., Senescence in human intervertebral discs. European Spine Journal, 2006. 15(3): p. 312-316.
11. Le Maitre, C.L., et al., Matrix synthesis and degradation in human intervertebral disc degeneration. Biochemical Society Transactions, 2007. 35(4): p. 652-655.
12. Freemont, A.J., The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology, 2009. 48(1): p. 5-10.
13. Lai, A., et al., Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section. JOR SPINE, 2021. 4(2): p. e1150.
14. Salzer, E., et al., Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue. JOR Spine, 2023. 6(1): p. e1240.
15. Hwang, P.Y., et al., The Role Of Extracellular Matrix Elasticity and Composition In Regulating the Nucleus Pulposus Cell Phenotype in the Intervertebral Disc: A Narrative Review. Journal of Biomechanical Engineering, 2014. 136(2).
16. Risbud, M.V. and I.M. Shapiro, Role of cytokines in intervertebral disc degeneration: pain and disc content. Nature Reviews Rheumatology, 2014. 10(1): p. 44-56.
17. Le Maitre, C.L., A.J. Freemont, and J.A. Hoyland, The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration. Arthritis Research & Therapy, 2005. 7(4): p. R732.
18. Le Maitre, C.L., J.A. Hoyland, and A.J. Freemont, Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1β and TNFα expression profile. Arthritis Research & Therapy, 2007. 9(4): p. R77.
19. Wang, Y., et al., The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomedicine & Pharmacotherapy, 2020. 131: p. 110660.
20. Chu, Y.-C., et al., Activation of mechanosensitive ion channels by ultrasound. Ultrasound in Medicine & Biology, 2022.
21. Ding, J., et al., ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration. Aging (Albany NY), 2021. 13(7): p. 10703-10723.
22. Wang, S., et al., Ultrasonic Neuromodulation and Sonogenetics: A New Era for Neural Modulation. Frontiers in Physiology, 2020. 11.
23. Velling, V.A. and S.P. Shklyaruk, Modulation of the functional state of the brain with the aid of focused ultrasonic action. Neurosci Behav Physiol, 1988. 18(5): p. 369-75.
24. Shin, J., et al., Electrical impulse effects on degenerative human annulus fibrosus model to reduce disc pain using micro-electrical impulse-on-a-chip. Scientific Reports, 2019. 9(1): p. 5827.
25. Poillot, P., et al., Piezoelectricity in the Intervertebral disc. Journal of Biomechanics, 2020. 102: p. 109622.
26. Lai, W.M., et al., On the Electric Potentials Inside a Charged Soft Hydrated Biological Tissue: Streaming Potential Versus Diffusion Potential. Journal of Biomechanical Engineering, 2000. 122(4): p. 336-346.
27. Yang, S., Y. Wang, and X. Liang Piezoelectric Nanomaterials Activated by Ultrasound in Disease Treatment. Pharmaceutics, 2023. 15, DOI: 10.3390/pharmaceutics15051338.
28. Fearing, B.V., et al., Mechanotransduction and cell biomechanics of the intervertebral disc. JOR SPINE, 2018. 1(3): p. e1026.
29. Kim, J.H., et al., Effect of Biphasic Electrical Current Stimulation on IL-1β–Stimulated Annulus Fibrosus Cells Using In Vitro Microcurrent Generating Chamber System. Spine, 2013. 38(22).
30. Guerin, S., et al., Control of piezoelectricity in amino acids by supramolecular packing. Nature Materials, 2018. 17(2): p. 180-186.
31. Poillot, P., C.L. Le Maitre, and J.M. Huyghe, The strain-generated electrical potential in cartilaginous tissues: a role for piezoelectricity. Biophysical Reviews, 2021. 13(1): p. 91-100.
32. Luo, Z., et al. Achilles’ Heel—The Significance of Maintaining Microenvironmental Homeostasis in the Nucleus Pulposus for Intervertebral Discs. International Journal of Molecular Sciences, 2023. 24, DOI: 10.3390/ijms242316592.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/98103-
dc.description.abstract椎間盤退化(Intervertebral Disc Degeneration, IDD)是造成下背痛的主要原因之一,目前治療方式多僅能暫時緩解症狀,難以促進組織再生,且部分侵入性療法可能進一步破壞椎間盤結構。研究顯示,椎間盤具壓電特性,在機械刺激下可產生局部電場,進而調控細胞行為與組織修復。

本研究建立小鼠尾椎椎間盤退化模型,並比較以硬式 PZT 與軟式 PVDF 壓電材料製成探頭進行低強度脈衝超音波(ISATA:33 mW/cm²)治療兩週之效果。實驗結果顯示,PVDF 探頭相較於 PZT 探頭能更有效抑制 TNF-α 與 IL-1β 的發炎表現,並在 ECM 組成方面提升 Collagen II 與 Aggrecan 表現,降低 Collagen I,尤以纖維環區恢復幅度最為明顯。

細胞實驗部分,建立含 RGD 的水凝膠三維髓核細胞培養系統,種植於石英(具壓電性)與玻璃(不具壓電性)片上,並搭配酸敏感通道(ASIC)抑制劑,探討超音波介導壓電刺激之機械反應。結果顯示,細胞核形態延展性整體變化不顯著,可能因本研究條件下細胞對形態指標較不敏感,需進一步優化觀察參數。

本研究結果提供低能量超音波與壓電材料應用於椎間盤修復之初步依據,並顯示 PVDF 具更佳生物相容性與刺激效率,具有非侵入性治療應用潛力。
zh_TW
dc.description.abstractIntervertebral disc degeneration (IDD) is a major cause of low back pain. Most current treatments only offer temporary relief and cannot repair damaged disc tissue. Some invasive procedures may even worsen the disc structure. Studies suggest that discs possess piezoelectric properties, generating local electric fields under mechanical stress that may support cell function and tissue repair.

In this study, we used a mouse tail model of disc degeneration and applied low-intensity pulsed ultrasound (ISATA: 33 mW/cm²) for two weeks using two types of piezoelectric materials: rigid PZT and flexible PVDF. Results showed that the PVDF probe was better than the PZT probe at reducing inflammation (TNF-α and IL-1β) and improving the expression of ECM proteins like Collagen II and Aggrecan, while lowering Collagen I. The improvement was most noticeable in the annulus fibrosus area.

In cell experiments, we created a 3D culture system using hydrogels with RGD peptides and seeded nucleus pulposus cells on quartz (piezoelectric) and glass (non-piezoelectric) surfaces. We also used an ASIC inhibitor to study how cells respond to piezoelectric ultrasound. The results showed only slight changes in nuclear shape, with no significant differences, suggesting that under these conditions, cells may not be very sensitive to the stimulus, or longer testing may be needed.

Overall, this study shows that low-intensity ultrasound combined with PVDF piezoelectric material has good potential for helping repair degenerated discs in a non-invasive way.
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dc.description.provenanceSubmitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-07-25T16:05:19Z
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dc.description.provenanceMade available in DSpace on 2025-07-25T16:05:19Z (GMT). No. of bitstreams: 0en
dc.description.tableofcontents致謝 I
摘要 II
ABSTRACT III
目次 IV
圖次 VI
表次 VIII
第一章緒論 1
1.1臨床背景:下背痛 1
1.2 椎間盤簡介 1
1.2.1髓核 2
1.2.2纖維環 2
1.2.3軟骨終版 2
1.2.4細胞外基質 3
1.3椎間盤退化 3
1.4發炎因子 5
1.4.1腫瘤壞死因子(TNF-α) 6
1.4.2白细胞介素1β(IL-1β) 6
1.5機械力敏感通道(MECHANOSENSITIVE CHANNELS, MSC) 7
1.6超音波簡介 7
1.7壓電效應簡介 9
1.8 椎間盤中的壓電性質 10
1.9超音波介導的壓電性質 10
1.10研究目的 11
第二章材料與方法 13
2.1研究方法介紹 13
2.2小鼠椎間盤退化模型建立實驗 14
2.2.1實驗設計 14
2.2.2生物檢測法 14
2.3治療小鼠椎間盤退化實驗 21
2.3.1實驗設計 21
2.3.2超音波治療裝置 22
2.3.3治療裝置架設 23
2.3.4能量量測 24
2.3.5升溫情形量測 25
2.3.6機械檢測法 27
2.3.7壓電檢測法 28
2.3.8生物檢測法 29
2.4髓核細胞水膠環境實驗 31
2.4.1髓核細胞初代培養(Primary Culture) 31
2.4.2髓核細胞的培養與繼代 32
2.4.3水凝膠(Hydrogel)介紹 33
2.4.4 3D水膠細胞培養環境實驗 33
2.5超音波介導壓電刺激酸敏感通道實驗 37
2.5.1實驗流程 37
2.5.2水膠穿刺模型建立 38
2.5.3脈衝超音波刺激裝置 39
2.6統計檢測方法 43
第三章實驗結果 44
3.1前導實驗(椎間盤壓電性質測試) 44
3.2小鼠椎間盤退化模型建立實驗結果 44
3.2.1退化分析報告 44
3.2.2退化椎間盤發炎反應實驗結果 46
3.2.3退化椎間盤細胞外基質變化實驗結果 47
3.3治療小鼠椎間盤退化實驗結果 48
3.3.1治療退化椎間盤分析報告 48
3.3.2治療退化椎間盤機械性質變化結果 50
3.3.3治療退化椎間盤發炎反應實驗結果 50
3.3.4治療退化椎間盤細胞外基質變化實驗結果 54
3.4髓核細胞水膠環境實驗結果 59
3.5超音波介導壓電刺激酸敏感通道實驗結果 60
第四章討論 62
4.1治療小鼠椎間盤退化實驗結果討論 62
4.2超音波介導壓電刺激酸敏感通道實驗結果討論 63
第五章結論 64
第六章未來展望 65
REFERENCE 66
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dc.language.isozh_TW-
dc.subject椎間盤退化zh_TW
dc.subject微能量超音波zh_TW
dc.subject壓電材料zh_TW
dc.subject髓核細胞zh_TW
dc.subjectASIC3zh_TW
dc.subjectnucleus pulposus cellsen
dc.subjectpiezoelectric materialen
dc.subjectASIC3en
dc.subjectIntervertebral disc degenerationen
dc.subjectlow-intensity ultrasounden
dc.title硬式 PZT 與軟式 PVDF 壓電探頭對退化椎間盤 細胞外基質與發炎反應之影響zh_TW
dc.titleEffects of Rigid PZT and Flexible PVDF Piezoelectric Probes on Extracellular Matrix and Inflammatory Response in Degenerated Intervertebral Discsen
dc.typeThesis-
dc.date.schoolyear113-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee陳志成;徐善慧zh_TW
dc.contributor.oralexamcommitteeChih-Cheng Chen;Shan-hui Hsuen
dc.subject.keyword椎間盤退化,髓核細胞,微能量超音波,壓電材料,ASIC3,zh_TW
dc.subject.keywordIntervertebral disc degeneration,nucleus pulposus cells,low-intensity ultrasound,piezoelectric material,ASIC3,en
dc.relation.page68-
dc.identifier.doi10.6342/NTU202501617-
dc.rights.note同意授權(限校園內公開)-
dc.date.accepted2025-07-17-
dc.contributor.author-college工學院-
dc.contributor.author-dept醫學工程學系-
dc.date.embargo-lift2030-07-07-
顯示於系所單位:醫學工程學研究所

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