| 研究生: |
李琪茹 Lee, Chi-Ju |
|---|---|
| 論文名稱: |
探討磷酸鈣與血小板濃縮液對急性旋轉肌群破損修復癒合的影響 Effect of Calcium-Phosphate and Platelet-Rich Plasma on Tendon-Bone Healing for Acute Rotator Cuff Tear Repairing |
| 指導教授: |
葉明龍
Yeh, Ming-Long 蘇維仁 Su, Wei-Ren |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 生物醫學工程學系 Department of BioMedical Engineering |
| 論文出版年: | 2017 |
| 畢業學年度: | 105 |
| 語文別: | 英文 |
| 論文頁數: | 77 |
| 中文關鍵詞: | 旋轉肌群 、棘上肌 、肌腱-骨頭癒合 、磷酸鈣 、血小板濃縮液 |
| 外文關鍵詞: | rotator cuff, supraspinatus, tendon-bone healing, calcium phosphate, platelet-rich plasma |
| 相關次數: | 點閱:258 下載:2 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
旋轉肌群破損影響相當多有年紀的病人,造成日常活動中的軟弱無力、功能障礙及一再發生的疼痛。由於棘上肌的解剖位置,導致該棘上肌特別容易在肌腱嵌入骨頭處破損,此處亦是分析指示高張應力與高壓應力處,且與臨床發現旋轉肌群經常發生破損處相關。雖然,旋轉肌群破損修復方法顯著地精進,為達最高可能的初始固定強度,然而,報告指出旋轉肌群破損修復後再次破損率仍高居不下,表明旋轉肌群癒合受到機械與生物因子組合的影響。旋轉肌群癒合關鍵性地決定臨床結果。目前,旋轉肌群破損修復後,在肌腱-骨頭介面多生成纖維血管性瘢痕組織,而非生成重要的原正常的纖維軟骨組織。過去研究指示,磷酸鈣(CaP)對於肌腱-骨頭介面癒合有助於新的骨頭生成、增加纖維軟骨形成及促進膠原蛋白組織等,且血小板濃縮液(PRP)內含癒合過程中需要的豐富生長因子與細胞激素,故而,本研究目的為探討磷酸鈣與血小板濃縮液對急性旋轉肌群破損修復癒合的影響。本研究假說為在急性旋轉肌群破損修復期間,磷酸鈣和血小板濃縮液的介入可改變生成纖維血管性瘢痕組織為生成纖維軟骨組織,增強肌腱-骨頭癒合。
總共六十四隻雄性Sprague-Dawley大鼠隨機分為兩批:(1)正常控制(N = 10),(2)手術介入(N = 54)。在正常控制批裡,沒有任何手術介入。其中,四隻大鼠用於定量PRP的製備過程,另外六隻大鼠用於製備CaP + PRP合成物。在手術介入批裡,五十四隻大鼠等分為三組:(1)無材料於缺陷處之控制組(Ctl組),(2)填補磷酸鈣實驗組(CaP組),(3)填補磷酸鈣及血小板濃縮液實驗組(CaP + PRP組)。所有組別中,每隻大鼠的兩隻肩膀都手術建立急性棘上肌破損模型,雙側棘上肌立即接受穿骨修復與相同的組別治療。在術後二週、四週和八週,棘上肌肌腱嵌入骨頭癒合處進行維度測量以評估橫截面積,生物力學測試以評估極限負荷、剛度、極限應力及失敗模式,組織學評估總體形態、膠原蛋白組織、附著處重建及新的纖維軟骨形成,及微觀電腦斷層掃描分析評估骨分佈、BMD、BV / TV及TbTh。
維度測量結果顯示,術後二週、四週及八週,3組間棘上肌肌腱嵌入骨頭癒合處之截面積無統計上差異。生物力學測試結果顯示,在術後四週,CaP + PRP組棘上肌肌腱嵌入骨頭癒合處之剛度統計上明顯大於Ctl控制組(P = 0.049)。在術後八週,CaP + PRP組棘上肌肌腱嵌入骨頭癒合處之極限負荷統計上明顯大於Ctl控制組(P = 0.015)。不論在任何時間點,CaP和CaP + PRP組間棘上肌肌腱嵌入骨頭癒合處之極限載荷、剛度及極限應力均無統計上差異。組織學結果顯示,棘上肌肌腱嵌入骨頭癒合處的整體形態在癒合期間逐漸成熟、連續與重整,此現象在CaP和CaP + PRP組別尤為明顯。此外,相較於術後二週,術後八週注意到規則結締組織與其癒合至骨頭。微觀CT分析結果顯示,除了在術後二週CaP + PRP組棘上肌肌腱嵌入骨頭癒合處之TbTh相較於Ctl控制組無統計上差異外,在術後二~八週,CaP和CaP + PRP組棘上肌肌腱嵌入骨頭癒合處之BMD、BV / TV及TbTh統計上均明顯大於Ctl控制組。本研究結論,在旋轉肌群修復期間,磷酸鈣和血小板濃縮液的介入可以增強肌腱-骨頭癒合且幫助改變目前生成纖維血管性瘢痕組織為生成纖維軟骨組織。
Rotator cuff tear affect a substantial number of patients as they age and lead to weakness, dysfunction and re-current pain during daily activities. By virtue of its anatomic location, the supraspinatus is particularly vulnerable to tear at the tendon-bone insertion site where high tensile and compressive stresses were noted analytically and correlated with clinical finding of frequent occurrence of rotator cuff tears at this site. Despite significant advances in repair methods to achieve the highest possible initial strength, re-tear rates after rotator cuff repair are commonly reported to be high, indicating rotator cuff healing is influenced by a combination of mechanical and biological factors and is critical for clinical outcomes. However, the current nature of tendon-bone healing after rotator cuff repair is still the formation of fibrovascular scar tissue at the tendon-bone interface rather than the formation of fibrocartilage which is the crucial structure in native tendon insertion. With previous evidences shown the positive effects of calcium phosphate (CaP) in new bone formation, increased fibrocartilage, and improved collagen organization at the healing tendon-bone interface and abundant growth factors and cytokines involved platelet-rich plasma (PRP) in healing process, the purpose of this research is to evaluate the effect of CaP and PRP on tendon-bone healing for acute rotator cuff tear repairing. The hypothesis of this research is that the incorporation of CaP and PRP materials during acute rotator cuff repair could enhance tendon-bone healing by changing the fibrovascular scar tissue formation into fibrocartilage formation.
A total of sixty-four male Sprague-Dawley rats were randomly allocated into two sets: (1) normal control (N=10), (2) surgical intervened (N=54). In the normal control set, no any surgical intervene was applied on them. Four of them were used to quantify the PRP preparation process, while the other six rats were used to prepare the CaP + PRP compound. In the surgical intervened set, fifty-four rats were equally allocated into3 groups: (1) control group without material applied on defect (Ctl group), (2) experiment group with CaP applied on defect (CaP group), and (3) experiment group with CaP and PRP applied on the defect (CaP + PRP group). Both shoulders of each rat in all groups were underwent acute transaction and immediately received and transosseous repair and treatment on the bilateral supraspinatus tendon. At 2, 4, and 8 weeks post-operatively, the supraspinatus tendon-bone healing enthesis was underwent dimensional measurement to evaluate cross-sectional area, biomechanical testing to evaluate ultimate load, stiffness, ultimate stress, and failure mode, histological assessment to evaluate overall morphology, collagen organization, footprint regeneration and new fibrocartilage formation, and micro-computed tomography analysis to evaluate bone distribution, BMD, BV/TV, and TbTh.
Dimensional measurement indicated that no statistical differences in the cross-sectional area of the SS tendon-bone healing enthesis were found between the 3 groups at 2, 4, and 8 weeks postoperatively. Biomechanical testing indicated that there was significantly greater stiffness of the SS tendon-bone healing enthesis in the CaP + PRP group compared with the Ctl control at 4 weeks postoperatively (P = .049). At 8 weeks postoperatively, there was significantly greater ultimate load of the SS tendon-bone healing enthesis in the CaP + PRP group compared with the Ctl control (P = .015). No significant differences in ultimate load, stiffness, and ultimate stress were found between the CaP and CaP + PRP groups at any time points. Histological assessment indicated that the overall morphology of SS tendon-bone healing enthesis became progressively matured, continuous, and re-organized during healing periods, which was particularly obvious in the CaP and CaP + PRP groups. Moreover, regular connective tissue and its healing to the bone were noticed at 8 weeks postoperatively compared with at 2 weeks postoperatively. Micro-CT analysis indicated that there was significantly greater BMD, BV/TV, and TbTh of the SS tendon-bone healing enthesis in the CaP and CaP + PRP groups compared with the Ctl control from 2 to 8 weeks postoperatively except the TbTh between the CaP + PRP group and Ctl control at 2 weeks postoperatively. We concluded that the CaP plus PRP can enhance tendon-bone healing and aid in changing its current nature of fibrovascular scar tissue formation into fibrocartilage formation in rotator cuff tendon repair.
1. Elsie Culham, Malcolm Peat. Functional Anatomy of the Shoulder Complex.JOSPT 1993; 18(1):342-350.
2. Marieb EN, Mallatt J, Wilhelm PB. Human anatomy (8th ed). San Francisco: Pearson Benhamin Cummings, 2008.
3. Longo UG, Berton A, Papapietro N, Maffulli N, Denaro V. Biomechanics of the rotator cuff: European perspective. Med Sport Sci. 2012; 57:10-17.
4. Sigholm G, Styf J, Korner L, Herberts P. Pressure recording in the subacromial bursa. J Orthop Res 1988; 6(1):123-128.
5. Mark A. Frankle. Rotator cuff deficiency of the shoulder. New York: Thieme Medical Publisher, Inc., 2008.
6. Itoi E, Berglund LJ, Grabowski JJ, Schultz FM, Growney ES, Morrey BF, An KN. Tensile properties of the supraspinatus tendon. J Orthop Res 1995; 13(4):578-584.
7. Nakajima T, Rokuuma N, Hamada K, Tomatsu T, Fukuda H. Histologic and biomechanical characteristics of the supraspinatus tendon: Reference to rotator cuff tearing. J Shoulder Elbow Surg 1994; 3(2):79-87.
8. Lee SB, Nakajima T, Luo ZP, Zobitz ME, Chang YW, An KN. The bursal and articular sides of the supraspinatus tendon have a different compressive stiffness. Clin Biomech (Bristol, Avon) 2000; 15(4):241-247.
9. Apostolakos J, Durant TJS, Dwyer CR, Russell RP, Weinreb JH, Alaee F, Beitzel K, McCarthy MBR, Cote MP, Mazzocca AD. The enthesis: a review of the tendon-to-bone insertion. Muscles, Ligaments and Tendons Journal 2014; 4(3):333-342.
10. Benjamin M, Ralphs JR. Entheses-the bony attachments of tendons and ligaments. Ital J Anat Embryol. 2001; 106(2 Suppl 1):151-157.
11. Lu HH, Thomopoulos S. Functional attachment of soft tissues to bone: development, healing, and tissue engineering. Annu Rev Biomed Eng. 2013; 15:201-226.
12. Benjamin M, Kumai T, Milz S, Boszczyk BM, Boszczyk AA, Ralphs JR. The skeletal attachment of tendons—tendon “entheses”. Comp Biochem Physiol A Mol Integr Physiol. 2002; 133(4):931-945.
13. Angeline ME, Rodeo SA. Biologics in the management of rotator cuff surgery. Clin Sports Med. 2012; 31(4):645-663.
14. Urwin M, Symmons D, Allison T, Brammah T, Busby H, Roxby M, Simmons A, Williams G. Estimating the burden of musculoskeletal disorders in the community: the comparative prevalence of symptoms at different anatomical sites, and the relation to social deprivation. Ann Rheum Dis 1998; 57:649-655.
15. Medscape. Rotator Cuff Pathology. http://emedicine.medscape.com/article/1262849-overview(Accessed May 10, 2017)
16. Longo UG, Berton A, Papapietro N, Maffulli N, Denaro V. Epidemiology, genetics and biological factors of rotator cuff tears. Med Sport Sci. 2012; 57:1-9.
17. Yamamoto A, Takagishi K, Osawa T, Yanagawa T, Nakajima D, Shitara H, Kobayashi T. Prevalence and risk factors of a rotator cuff tear in the general population. J Shoulder Elbow Surg 2010; 19(1):116-120.
18. Minagawa H, Yamamoto N, Abe H, Fukuda M, Seki N, Kikuchi K, Kijima H, Itoi E. Prevalence of symptomatic and asymptomatic rotator cuff tears in the general population: From mass-screening in one village. J Orthop 2013; 10(1):8-12.
19. Harryman DT 2nd, Hettrich CM, Smith KL, Campbell B, Sidles JA, Matsen FA 3rd. A prospective multipractice investigation of patients with full-thickness rotator cuff tears: the importance of comorbidities, practice, and other covariables on self-assessed shoulder function and health status. J Bone Joint Surg Am 2003; 85:690-696.
20. Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA. The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am 2006; 88(8):1699-1704.
21. Neer CS II and Poppen NK. Supraspinatus outlet. Orthop Trans 1987; 11:234.
22. Bigliani LU, Ticker JB, Flatow EL, Soslowsky LJ, Mow VC. The relationship of acromial architecture to rotator cuff disease. Clin Sports Med 1991; 10:823-838.
23. Rees JD, Wilson AM, Wolman RL. Current concepts in the management of tendon disorders. Rheumatology (Oxford) 2006; 45(5):508-521.
24. Wang JC, Shapiro MS. Changes in acromial morphology with age. J Shoulder Elbow Surg 1997; 6:55-59.
25. Yadav H, Nho S, Romeo A, MacGillivray JD. Rotator cuff tears: pathology and repair. Knee Surgery Sports Traumatology Arthroscopy 2009; 17(4):409-421.
26. Galatz LM, Sandell LJ, Rothermich SY, Das R, Mastny A, Havlioglu N, Silva MJ, Thomopoulos S. Characteristics of the rat supraspinatus tendon during tendon-to-bone healing after acute injury. J Orthop Res 2006; 24(3):541-550.
27. Tsuzaki M, Guyton G, Garrett W, Archambault JM, Herzog W, Almekinders L, Bynum D, Yang X, Banes AJ. IL-1β induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells. J Orthop Res 2003; 21:256-264.
28. LeGeros RZ. Calcium phosphate-based osteoinductive materials. Chemical reviews 2008; 108(11):4742-4753.
29. Tien YC, Chih TT, Lin JHC, Ju CP, Lin SD. Augmentation of tendon-bone healing by the use of calcium-phosphate cement. Journal of Bone and Joint Surgery (British Volume) 2004; 86B(7):1072-1076.
30. Zhao S, Peng L, Xie G, Li D, Zhao J, Ning C. Effect of the Interposition of Calcium Phosphate Materials on Tendon-Bone Healing During Repair of Chronic Rotator Cuff Tear. Am J Sports Med 2014; 42(8):1920-1929.
31. Kovacevic D, Fox AJ, Bedi A, Ying L, Deng XH, Warren RF, Rodeo SA. Calcium-phosphate matrix with or without TGF-beta3 improves tendon-bone healing after rotator cuff repair. Am J Sports Med 2011; 39(4):811-819.
32. Wu Y, Dong Y, Chen SY, Li YX. Effect of Platelet-Rich Plasma and Bioactive Glass Powder for the Improvement of Rotator Cuff Tendon-to-Bone Healing in a Rabbit Model. International Journal of Molecular Sciences 2014; 15(12):21980-21991.
33. Soslowsky LJ, Carpenter JE, DeBano CM, Banerji I, Moalli MR. Development and use of an animal model for investigations on rotator cuff disease. J Shoulder Elbow Surg 1996; 5(5):383-392.
34. Bell R, Taub P, Cagle P, Flatow EL, Andarawis-Puri N. Development of a mouse model of supraspinatus tendon insertion site healing. J Orthop Res 2015; 33(1):25-32.
35. Gupta R, Lee TQ. Contributions of the different rabbit models to our understanding of rotator cuff pathology. J Shoulder Elbow Surg 2007; 16(5 Suppl):S149-S157.
36. Rowshan K, Hadley S, Pham K, Caiozzo V, Lee TQ, Gupta R. Development of fatty atrophy after neurologic and rotator cuff injuries in an animal model of rotator cuff pathology. J Bone Joint Surg Am 2010; 92(13):2270-2278.
37. Edelstein L, Thomas SJ, Soslowsky LJ. Rotator Cuff Tears: What have we learned from animal models? J Musculoskelet Neuronal Interact. 2011; 11(2):150-162.
38. Carpenter JE, Thomopoulos S, Flanagan CL, DeBano CM, Soslowsky LJ. Rotator cuff defect healing: a biomechanical and histologic analysis in an animal model. J Shoulder Elbow Surg 1998; 7(6):599-605.
39. Dolkart O, Chechik O, Zarfati Y, Brosh T, Alhajajra F, Maman E. A single dose of platelet-rich plasma improves the organization and strength of a surgically repaired rotator cuff tendon in rats. Arch Orthop Trauma Surg 2014; 134(9):1271-1277.
40. Ide J, Tokiyoshi A, Hirose J, Mizuta H. An anatomic study of the subscapularis insertion to the humerus: the subscapularis footprint. Arthroscopy 2008; 24(7):749-753.
41. Tierney J, Curtis A, Kowalik D, Scheller A. The footprint of the rotator cuff. Arthroscopy 1999; 15(5):556-557.
42. Curtis AS, Burbank KM, Tierney JJ, Scheller AD, Curran AR. The insertional footprint of the rotator cuff: An anatomic study. Arthroscopy 2006; 22(6):603-609.
43. Dugas JR, Campbell DA, Warren RF, Robie BH, Millett PJ. Anatomy and dimensions of rotator cuff insertions. J Shoulder Elb Surg 2002; 11(5):498-503.
44. Lumsdaine W, Smith A, Walker RG, Benz D, Mohammed KD, Stewart F. Morphology of the humeral insertion of the supraspinatus and infraspinatus tendons: Application to rotator cuff repair. Clinical Anatomy 2015; 28(6):767-773.
45. Plate JF, Brown PJ, Walters J, Clark JA, Smith TL, Freehill MT et al. Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair. The American journal of sports medicine 2014; 42(4):859-868.
46. Barber FA. Platelet-rich plasma for rotator cuff repair. Sports Medicine and Arthroscopy Review 2013; 21(4):199-205.
47. Plate JF, Brown PJ, Walters J, Clark JA, Smith TL, Freehill MT, Tuohy CJ, Stitzel JD, Mannava S. Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair. Am J Sports Med 2014; 42(4):859-868.
48. Wikipedia: Platelet-rich plasma. https://en.wikipedia.org/wiki/Platelet-rich_plasma (Accessed May 15, 2017)
49. Ersen A, Demirhan M, Atalar AC, Kapicioglu M, Baysal G. Platelet-rich plasma for enhancing surgical rotator cuff repair: evaluation and comparison of two application methods in a rat model. Arch Orthop Trauma Surg 2014; 134(3):405-411.
50. Hapa O, Cakici H, Kukner A, Aygun H, Sarkalan N, Baysal G. Effect of platelet-rich plasma on tendon-to-bone healing after rotator cuff repair in rats: an in vivo experimental study. Acta Orthop Traumatol Turc 2012; 46(4):301-307.