Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  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/123456789/15587
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor林峯輝(Feng-Huei Lin)
dc.contributor.authorYu-Min Huangen
dc.contributor.author黃裕閔zh_TW
dc.date.accessioned2021-06-07T17:48:20Z-
dc.date.copyright2020-08-06
dc.date.issued2020
dc.date.submitted2020-08-04
dc.identifier.citation1. Beynnon, B. D.; Johnson, R. J.; Fleming, B. C.; Peura, G. D.; Renstrom, P. A.; Nichols, C. E.; Pope, M. H. The effect of functional knee bracing on the anterior cruciate ligament in the weightbearing and nonweightbearing knee. Am J Sports Med 1997, 25, 353–359.
2. Amis, A. A.; Dawkins, G. P. Functional anatomy of the anterior cruciate ligament. Fibre bundle actions related to ligament replacements and injuries. J Bone Joint Surg Br 1991, 73, 260–267.
3. Girgis, F. G.; Marshall, J. L.; Monajem, A. The cruciate ligaments of the knee joint. Anatomical, functional and experimental analysis. Clin. Orthop. Relat. Res. 1975, 106, 216–231.
4. Gabriel, M. T.; Wong, E. K.; Woo, S. L.-Y.; Yagi, M.; Debski, R. E. Distribution of in situ forces in the anterior cruciate ligament in response to rotatory loads. J. Orthop. Res. 2004, 22, 85–89.
5. Duthon, V. B.; Barea, C.; Abrassart, S.; Fasel, J. H.; Fritschy, D.; Ménétrey, J. Anatomy of the anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 2006, 14, 204–213.
6. Matsumoto, H.; Suda, Y.; Otani, T.; Niki, Y.; Seedhom, B. B.; Fujikawa, K. Roles of the anterior cruciate ligament and the medial collateral ligament in preventing valgus instability. J Orthop Sci 2001, 6, 28–32.
7. Nwachukwu, B. U.; Patel, B. H.; Lu, Y.; Allen, A. A.; Williams, R. J. Anterior Cruciate Ligament Repair Outcomes: An Updated Systematic Review of Recent Literature. Arthroscopy 2019, 35, 2233–2247.
8. Freedman, K. B.; D'Amato, M. J.; Nedeff, D. D.; Kaz, A.; Bach, B. R. Arthroscopic anterior cruciate ligament reconstruction: A metaanalysis comparing patellar tendon and hamstring tendon autografts. Am J Sports Med 2003, 31, 2–11.
9. Poehling-Monaghan, K. L.; Salem, H.; Ross, K. E.; Secrist, E.; Ciccotti, M. C.; Tjoumakaris, F.; Ciccotti, M. G.; Freedman, K. B. Long-term outcomes in anterior cruciate ligament reconstruction: A systematic review of patellar tendon versus hamstring autografts. Orthopaedic Journal of Sports Medicine 2017, 5, 2325967117709735.
10. Gifstad, T.; Foss, O. A.; Engebretsen, L.; Lind, M.; Forssblad, M.; Albrektsen, G.; Drogset, J. O. Lower risk of revision with patellar tendon autografts compared with hamstring autografts: a registry study based on 45,998 primary ACL reconstructions in Scandinavia. Am J Sports Med 2014, 42, 2319–2328.
11. Samuelsen, B. T.; Webster, K. E.; Johnson, N. R.; Hewett, T. E.; Krych, A. J. Hamstring Autograft versus Patellar Tendon Autograft for ACL Reconstruction: Is There a Difference in Graft Failure Rate? A Meta-analysis of 47,613 Patients. Clin. Orthop. Relat. Res. 2017, 475, 2459–2468.
12. Cooper, R. R.; Misol, S. Tendon and ligament insertion. A light and electron microscopic study. The Journal of Bone Joint Surgery 1970, 52, 1–20.
13. Rodeo, S. A.; Suzuki, K.; Deng, X.-H.; Wozney, J.; Warren, R. F. Use of Recombinant Human Bone Morphogenetic Protein-2 to Enhance Tendon Healing in a Bone Tunnel. Am J Sports Med 1999, 27, 476–488.
14. Wong, M. W. N.; Qin, L.; Tai, J. K. O.; Lee, S. K. M.; Leung, K. S.; Chan, K. M. Engineered allogeneic chondrocyte pellet for reconstruction of fibrocartilage zone at bone-tendon junction?A preliminary histological observation. Journal of Biomedical Materials Research 2004, 70B, 362–367.
15. Tomita, F.; Yasuda, K.; Mikami, S.; Sakai, T.; Yamazaki, S.; Tohyama, H. Comparisons of intraosseous graft healing between the doubled flexor tendon graft and the bone-patellar tendon-bone graft in anterior cruciate ligament reconstruction. Arthroscopy 2001, 17, 461–476.
16. Chen, G.; Hoffman, A. S. Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 1995, 373, 49–52.
17. Lin, Z.; Gao, W.; Hu, H.; Ma, K.; He, B.; Dai, W.; Wang, X.; Wang, J.; Zhang, X.; Zhang, Q. Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity. J Control Release 2014, 174, 161–170.
18. Ruel-Gariépy, E.; Chenite, A.; Chaput, C.; Guirguis, S.; Leroux, J. Characterization of thermosensitive chitosan gels for the sustained delivery of drugs. Int J Pharm 2000, 203, 89–98.
19. Chenite, A.; Chaput, C.; Wang, D.; Combes, C.; Buschmann, M. D.; Hoemann, C. D.; Leroux, J. C.; Atkinson, B. L.; Binette, F.; Selmani, A. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 2000, 21, 2155–2161.
20. Ahmadi, R.; de Bruijn, J. D. Biocompatibility and gelation of chitosan-glycerol phosphate hydrogels. J Biomed Mater Res A 2008, 86, 824–832.
21. Roughley, P.; Hoemann, C.; DesRosiers, E.; Mwale, F.; Antoniou, J.; Alini, M. The potential of chitosan-based gels containing intervertebral disc cells for nucleus pulposus supplementation. Biomaterials 2006, 27, 388–396.
22. Huang, Y.; Onyeri, S.; Siewe, M.; Moshfeghian, A.; Madihally, S. V. In vitro characterization of chitosan-gelatin scaffolds for tissue engineering. Biomaterials 2005, 26, 7616–7627.
23. Cheng, Y.-H.; Yang, S.-H.; Su, W.-Y.; Chen, Y.-C.; Yang, K.-C.; Cheng, W. T.-K.; Wu, S.-C.; Lin, F.-H. Thermosensitive chitosan-gelatin-glycerol phosphate hydrogels as a cell carrier for nucleus pulposus regeneration: an in vitro study. Tissue Engineering Part A 2010, 16, 695–703.
24. Chang, C.-H.; Chen, C.-H.; Liu, H.-W.; Whu, S.-W.; Chen, S.-H.; Tsai, C.-L.; Hsiue, G.-H. Bioengineered periosteal progenitor cell sheets to enhance tendon‑bone healing in a bone tunnel. Biomedical 2012, 35, 473–8.
25. Gulotta, L. V.; Kovacevic, D.; Ying, L.; Ehteshami, J. R.; Montgomery, S.; Rodeo, S. A. Augmentation of tendon-to-bone healing with a magnesium-based bone adhesive. Am J Sports Med 2008, 36, 1290–1297.
26. Goradia, V. K.; Rochat, M. C.; Kida, M.; Grana, W. A. Natural history of a hamstring tendon autograft used for anterior cruciate ligament reconstruction in a sheep model. Am J Sports Med 2000, 28, 40–46.
27. Grana, W. A.; Egle, D. M.; Mahnken, R.; Goodhart, C. W. An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med 1994, 22, 344–351.
28. Bedi, A.; Kawamura, S.; Ying, L.; Rodeo, S. A. Differences in tendon graft healing between the intra-articular and extra-articular ends of a bone tunnel. HSS Jrnl 2009, 5, 51–57.
29. Smith, P. A.; Stannard, J. P.; Pfeiffer, F. M.; Kuroki, K.; Bozynski, C. C.; Cook, J. L. Suspensory Versus Interference Screw Fixation for Arthroscopic Anterior Cruciate Ligament Reconstruction in a Translational Large-Animal Model. Arthroscopy 2016, 32, 1086–1097.
30. Yamazaki, S.; Yasuda, K.; Tomita, F.; Tohyama, H.; Minami, A. The effect of transforming growth factor-β1 on intraosseous healing of flexor tendon autograft replacement of anterior cruciate ligament in dogs. Arthroscopy: The Journal of Arthroscopic Related Surgery 2005, 21, 1034–1041.
31. Lovric, V.; Chen, D.; Yu, Y.; Oliver, R. A.; Genin, F.; Walsh, W. R. Effects of Demineralized Bone Matrix on Tendon-Bone Healing in an Intra-articular Rodent Model. Am J Sports Med 2012, 40, 2365–2374.
32. Lu, J.; Chamberlain, C. S.; Ji, M.-L.; Saether, E. E.; Leiferman, E. M.; Li, W.-J.; Vanderby, R. Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow-Derived Mesenchymal Stem Cells. Am J Sports Med 2019, 47, 2729–2736.
33. Yonemitsu, R.; Tokunaga, T.; Shukunami, C.; Ideo, K.; Arimura, H.; Karasugi, T.; Nakamura, E.; Ide, J.; Hiraki, Y.; Mizuta, H. Fibroblast Growth Factor 2 Enhances Tendon-to-Bone Healing in a Rat Rotator Cuff Repair of Chronic Tears. Am J Sports Med 2019, 47, 1701–1712.
34. Wong, C.-C.; Yeh, Y.-Y.; Yang, T.-L.; Tsuang, Y.-H.; Chen, C.-H. Augmentation of Tendon Graft-Bone Tunnel Interface Healing by Use of Bioactive Platelet-Rich Fibrin Scaffolds. Am J Sports Med 2020, 48, 1379–1388.
35. Yoon, J. P.; Chung, S. W.; Jung, J. W.; Lee, Y. S.; Kim, K. I.; Park, G. Y.; Kim, H. M.; Choi, J. H. Is a Local Administration of Parathyroid Hormone Effective to Tendon‐to‐Bone Healing in a Rat Rotator Cuff Repair Model? J. Orthop. Res. 2019, 38, 82–91.
36. Mutsuzaki, H.; Fujie, H.; Nakajima, H.; Fukagawa, M.; Nomura, S.; Sakane, M. Effect of Calcium Phosphate–Hybridized Tendon Graft in Anatomic Single-Bundle ACL Reconstruction in Goats. Orthopaedic Journal of Sports Medicine 2016, 4, 232596711666265–8.
37. Talhouk, R. S.; Bissell, M. J.; Werb, Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J. Cell Biol. 1992, 118, 1271–1282.
38. Bramono, D. S.; Richmond, J. C.; Weitzel, P. P.; Kaplan, D. L.; Altman, G. H. Matrix metalloproteinases and their clinical applications in orthopaedics. Clin. Orthop. Relat. Res. 2004, 428, 272–285.
39. de Mos, M.; van El, B.; DeGroot, J.; Jahr, H.; van Schie, H. T. M.; van Arkel, E. R.; Tol, H.; Heijboer, R.; van Osch, G. J. V. M.; Verhaar, J. A. N. Achilles tendinosis: changes in biochemical composition and collagen turnover rate. Am J Sports Med 2007, 35, 1549–1556.
40. Jones, G. C.; Corps, A. N.; Pennington, C. J.; Clark, I. M.; Edwards, D. R.; Bradley, M. M.; Hazleman, B. L.; Riley, G. P. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum. 2006, 54, 832–842.
41. Lavagnino, M.; Arnoczky, S. P.; Egerbacher, M.; Gardner, K. L.; Burns, M. E. Isolated fibrillar damage in tendons stimulates local collagenase mRNA expression and protein synthesis. J Biomech 2006, 39, 2355–2362.
42. September, A. V.; Cook, J.; Handley, C. J.; van der Merwe, L.; Schwellnus, M. P.; Collins, M. Variants within the COL5A1 gene are associated with Achilles tendinopathy in two populations. British Journal of Sports Medicine 2009, 43, 357–365.
43. Bedi, A.; Kovacevic, D.; Hettrich, C.; Gulotta, L. V.; Ehteshami, J. R.; Warren, R. F.; Rodeo, S. A. The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model. Journal of Shoulder and Elbow Surgery 2010, 19, 384–391.
44. Haslauer, C. M.; Proffen, B. L.; Johnson, V. M.; Murray, M. M. Expression of modulators of extracellular matrix structure after anterior cruciate ligament injury. Wound Repair Regen 2014, 22, 103–110.
45. Demirag, B.; Sarisozen, B.; Ozer, O.; Kaplan, T.; Ozturk, C. Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases. The Journal of Bone Joint Surgery 2005, 87, 2401–2410.
46. Paiva, K. B. S.; Granjeiro, J. M. Bone tissue remodeling and development: focus on matrix metalloproteinase functions. Arch. Biochem. Biophys. 2014, 561, 74–87.
47. Kylmaoja, E.; Nakamura, M.; Tuukkanen, J. Osteoclasts and Remodeling Based Bone Formation. Curr Stem Cell Res Ther 2016, 11, 626–633.
48. Chen, Y.-J.; Wang, C.-J.; Yang, K. D.; Kuo, Y.-R.; Huang, H.-C.; Huang, Y.-T.; Sun, Y.-C.; Wang, F.-S. Extracorporeal shock waves promote healing of collagenase-induced Achilles tendinitis and increase TGF-beta1 and IGF-I expression. J. Orthop. Res. 2004, 22, 854–861.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15587-
dc.description.abstract背景:前十字韌帶斷裂是膝蓋常見的疾病,當發生斷裂時會造成相當程度的功能喪失,手術重建前十字韌帶是目前治療的標準,然而韌帶重建的過程會有韌帶及骨頭癒合不良的問題,此一問題會造成復健的困難及影響手術的成功率,此研究是希望利用溫感水凝膠與酵素融釋的方式來解決骨韌帶癒合之問題,以期開發能臨床使用於前十字韌帶重建手術。
方法:將不同濃度的酵素及溫感水凝膠施行體外實驗,進行細胞毒性及酵素釋放效率測試後決定最適當之酵素濃度。接著進行兔子的動物實驗,取用兔子的長伸趾肌腱及脛骨長軸進行骨韌帶癒合之研究,利用36隻紐西蘭白兔的雙膝施作動物實驗,溫感水凝膠及酵素於手術時注射治療,術後進行組織切片檢查、斷層掃描、韌帶拉力測試來檢驗酵素融釋的效果。
結果與討論:酵素的體外實驗證實使用溫感水凝膠合併酵素可以有效促進韌帶的自我修復能力且無明顯細胞毒性,進行兔子動物實驗的切片檢查可見在四週及八週都有明顯的組織增生,且於八週時有明顯新生骨行成,斷層掃描可見於八週有顯著新生骨組織於酵素治療組,拉力測試可見酵素融釋可促進66%的最大荷重,證實使用溫感水凝膠合併酵素治療可有效促進骨韌帶癒合。
結論:溫感水凝膠與酵素融釋能成功促進骨韌帶癒合及新生骨的形成,並且提高生物力學的穩定性。這些結果表明溫感水凝膠與酵素融釋將可能使用前十字韌帶重建手術上。
zh_TW
dc.description.abstractBackground: Anterior cruciate ligament rupture is one of the most commonly injured structure in the knee joint, which induces severe comorbidity and functional deficits. Anterior cruciate ligament reconstruction is the gold standard treatment now. However, healing of an anterior cruciate ligament in bone tunnel yields weaker fibrous scar tissue, which may prolong the healing process within the tendon-bone interface. Poor tendon-bone healing may cause delay rehabilitation program and poor surgical results. In this study, we applied thermosensitive hydrogel with enzyme digestion to improve the healing process between tendon-bone interface.
Methods: In vitro study, we evaluated the different concentration enzyme to promote tendon graft healing. Cytotoxic test and enzyme release profile were also identified for the optimal enzyme concentration. New Zealand’s white rabbit’s long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection with and without collagenase. After scarifying, we performed histological examination, computed tomography imaging, and biomechanical test to evaluate the effect of collagenase partial digestion on tendon-bone healing.
Results Discussion: In vitro study, better tendon healing was illustrated after collagenase partial digestion with thermosensitive hydrogel. Cytotoxic and collagenase release profile was also identified. In rabbit animal study, histological analyses revealed early healing and more bone formation at the tendon-bone interface after collagenase partial digestion. Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks in the study group. Load-to-failure was significantly higher in the treated group at 8 weeks. Treatment with collagenase digestion resulted in a. 66% increase in pull-out-strength.
Conclusions: Injection of thermosensitive hydrogel with collagenase improves tendon-to-bone healing and more woven bone formation in a rabbit model. These results demonstrate that thermosensitive hydrogels with collagenase are potential candidates for clinical applications in anterior cruciate ligament reconstruction surgery.
en
dc.description.provenanceMade available in DSpace on 2021-06-07T17:48:20Z (GMT). No. of bitstreams: 1
U0001-0308202021463400.pdf: 22681469 bytes, checksum: d9700a8de49b950f9487589f79c28f02 (MD5)
Previous issue date: 2020
en
dc.description.tableofcontents中文摘要..............................................................................I Abstract..............................................................................II
目錄....................................................................................IV
圖目錄.................................................................................VI
表目錄.................................................................................VII
Chapter 1 Introduction....................................................................1
1.1 Anterior cruciate Ligament Anatomy..........................................1
1.2 Anterior cruciate Ligament reconstruction surgery...................7
1.3 Thermosensitive hydrogel........................................................ 8
Chapter 2 Materials and methods...................................................10
2.1 In vitro study..............................................................................10
2.1.1 Collagenase hydrogel preparation...........................................10
2.1.2 Collagenase concentration......................................................10
2.1.3 Cytotoxic test..........................................................................11
2.1.4 Release profile of collagenase from thermosensitive hydrogel...13
2.2 In vivo study..............................................................................14
2.2.1 Animal study design................................................................14
2.2.2 Surgical procedure..................................................................16
2.2.3 Histological examination.........................................................18
2.2.4 Micro-computed tomography evaluation................................18
2.2.5 Biomechanical Testing............................................................19
2.2.6 Statistical analyses.................................................................20
Chapter 3 Results............................................................................21
3.1 In vitro study...............................................................................21
3.1.1 Collagenase concentration evaluation.....................................21
3.1.2 Cytotoxic test..........................................................................23
3.1.3 Release profile of collagenase from thermosensitive hydrogel...25
3.2 In vivo study...............................................................................27
3.2.1 Gross observations..................................................................27
3.2.2 Histologic analysis .................................................................29
3.2.3 Micro-computed tomography evaluation................................35
3.2.4 Biomechanical test..................................................................38
Chapter 4 Discussions.....................................................................41
Chapter 5 Conclusions and Suggestions.........................................45
5.1 Conclusions................................................................................45
5.2 Suggestions and Future studies.................................................46
Chapter 6 References.......................................................................47
dc.language.isoen
dc.subject骨韌帶癒合zh_TW
dc.subject前十字韌帶zh_TW
dc.subject酵素融釋zh_TW
dc.subject溫感水凝膠zh_TW
dc.subject組織工程zh_TW
dc.subjecttendon-bone healingen
dc.subjectthermosensitive hydrogelen
dc.subjectanterior cruciate ligamenten
dc.subjecttissue engineeringen
dc.subjectcollagenase digestionen
dc.title溫感水凝膠及酵素部分融釋於骨韌帶癒合之研究zh_TW
dc.titleThermosensitive Hydrogel and Partial Enzyme Digestion on Tendon-Bone Healingen
dc.typeThesis
dc.date.schoolyear108-2
dc.description.degree博士
dc.contributor.coadvisor曾永輝(Yang-Hwei Tsuang),陳志華(Chih-Hwa Chen)
dc.contributor.oralexamcommittee孫瑞昇(Jui-Sheng Sun),劉燦宏(Tsan-Hon Liou)
dc.subject.keyword溫感水凝膠,酵素融釋,骨韌帶癒合,前十字韌帶,組織工程,zh_TW
dc.subject.keywordthermosensitive hydrogel,collagenase digestion,tendon-bone healing,anterior cruciate ligament,tissue engineering,en
dc.relation.page55
dc.identifier.doi10.6342/NTU202002322
dc.rights.note未授權
dc.date.accepted2020-08-05
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
顯示於系所單位:醫學工程學研究所

文件中的檔案:
檔案 大小格式 
U0001-0308202021463400.pdf
  未授權公開取用
22.15 MBAdobe PDF
顯示文件簡單紀錄


系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved