ONUR HAPA, HÜSAMETTİN ÇAKICI, AYSEL KÜKNER, Hayati AYGÜN, Nazlı SARKALAN, Gökhan BAYSAL

Effect of platelet-rich plasma on tendon-to-bone healing after rotator cuff repair in rats: an in vivo experimental study

Amaç: Bu çalışmanın amacı sıçan rotator manşet yaralanması modelinde lokal otolog trombositten zengin plazma (TZP) enjeksiyonunun tendon-kemik iyileşmesine etkisini incelemekti. Çalışma planı: Altmış sekiz sıçanın sol omuzunda rotator manşet yaralanması oluşturuldu. On beş sıçan ise trombositten zengin plazma oluşturmak için kullanıldı. Sıçanlar her grupta 17 adet olmak üzere 4 gruba ayrıldı; TZP grubu (2. hafta), kontrol grubu (2. hafta), TZP grubu (4. hafta), ve kontrol grubu (4. hafta). Trombositten zengin plazma veya serum fizyolojik operasyon sırasında onarım bölgesine enjekte edildi. Cerrahiden iki ve dört hafta sonrasında fareler sakrifiye edildi. Semikantitatif skorlamayla her gruptan 7 sıçan üzerinde histolojik değerlendirme yapıldı. Damarlanma artışı, iltihabi hücre miktarı, yeni kemik oluşum miktarı ve tendon devamlılığı değerlendirildi. Geri kalan tendonlar mekanik olarak test edildi (n=10). Bulgular: İltihaplanma miktarı ve damarlanma çalışma grubunda her iki zaman diliminde de daha azdı (p

Trombositten zengin plazmanın rotator manşet tendon-kemik iyileşmesine etkileri

Objective: The purpose of this experimental study was to analyze the effects of local autologous platelet-rich plasma (PRP) injection on tendon-to-bone healing in a rotator cuff repair model in rats. Methods: Rotator cuff injury was created in 68 left shoulders of rats. PRP was obtained from the blood of an additional 15 rats. The 68 rats were divided into 4 groups with 17 rats in each group; PRP group (Week 2), control group (Week 2), PRP group (Week 4), and control group (Week 4). Platelet-rich plasma or saline was injected to the repair area intraoperatively. Rats were sacrificed 2 and 4 weeks after the surgery. Histological analysis using a semiquantitative scoring was performed on 7 rats per group. Tendon integrity and increases in vascularity and inflammatory cells and the degree of new bone formation were evaluated and compared between the groups. The remaining tendons (n=10) were mechanically tested. Results: Degree of inflammation and vascularity were less in the study group at both time intervals (p<0.05). Tendon continuity was better in the study group at 2 weeks (p<0.05). Obvious new bone formation was detected in the control group at 4 weeks (p<0.05). Biomechanically, platelet-rich plasma-treated specimens were stronger at 2 weeks (p<0.05). Conclusion: Local autologous PRP injection may have beneficial effects on initial rotator cuff tendon-to-bone healing and enhance initial tendon-to-bone healing remodeling. This may represent a clinically important improvement in rotator cuff repair.

___

1. Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair integrity of complete- ly arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am 2004;86-A:219-24.
2. Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF. Tendon healing in a bone tunnel. A biomechanical and histo- logical study in the dog. J Bone Joint Surg Am 1993;75:1795- 803.
3. Cohen DB, Kawamura S, Ehteshami JR, Rodeo SA. Indomethacin and celecoxib impair rotator cuff tendon-to- bone healing. Am J Sports Med 2006;34:362-9.
4. Gamradt SC, Rodeo SA, Warren RF. Platelet-rich plasma in rotator cuff repair. Tech Orthop 2007;22:26-33.
5. Lopez-Vidriero E, Goulding KA, Simon DA, Sanchez M, Johnson DH. The use of platelet-rich plasma in arthroscopy and sports medicine: optimizing the healing environment. Arthroscopy 2010;26:269-78.
6. Anitua E, Andía I, Sanchez M, Azofra J, del Mar Zalduendo M, de la Fuente M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res 2005;23:281-6.
7. de Mos M, van der Windt AE, Jahr H, van Schie HT, Weinans H, Verhaar JA, et al. Can platelet-rich plasma enhance tendon repair? A cell culture study. Am J Sports Med 2008;36:1171-8.
8. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med 2006;34: 1774-8.
9. Kon E, Filardo G, Delcogliano M, Presti ML, Russo A, Bondi A, et al. Platelet-rich plasma: new clinical application: a pilot study for treatment of jumper's knee. Injury 2009;40: 598-603.
10. Sanchez M, Anitua E, Cugat R, Azofra J, Guadilla J, Seijas R, et al. Nonunions treated with autologous preparation rich in growth factors. J Orthop Trauma 2009;23:52-9.
11. Sánchez M, Anitua E, Azofra J, Andía I, Padilla S, Mujika I. Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med 2007;35:245- 51.
12. Sun Y, Feng Y, Zhang CQ, Chen SB, Cheng XG. The regen- erative effect of platelet-rich plasma on healing in large osteo- chondral defects. Int Orthop 2010;34:589-97.
13. Hammond JW, Hinton RY, Curl LA, Muriel JM, Lovering RM. Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med 2009;37:1135-42.
14. Castricini R, Longo UG, De Benedetto M, Panfoli N, Pirani P, Zini R, et al. Platelet-rich plasma augmentation for arthro- scopic rotator cuff repair: a randomized controlled trial. Am J Sports Med 2011;39:258-65.
15. Barber FA, Hrnack SA, Snyder SJ, Hapa O. Rotator cuff repair healing influenced by platelet-rich plasma construct augmentation. Arthroscopy 2011;27:1029-35.
16. Manning CN, Kim HM, Sakiyama-Elbert S, Galatz LM, Havlioglu N, Thomopoulos S. Sustained delivery of trans- forming growth factor beta three enhances tendon-to-bone healing in a rat model. J Orthop Res 2011;29:1099-105.
17. Kim HM, Galatz LM, Das R, Havlioglu N, Rothermich SY, Thomopoulos S The role of transforming growth factor beta isoforms in tendon-to-bone healing. Connect Tissue Res 2011; 52:87-98.
18. Rodeo SA, Potter HG, Kawamura S, Turner AS, Kim HJ, Atkinson BL. Biologic augmentation of rotator cuff tendon- healing with use of a mixture of osteoinductive growth fac- tors. J Bone Joint Surg Am 2007;89:2485-97.
19. Ide J, Kikukawa K, Hirose J, Iyama K, Sakamoto H, Fujimoto T, et al. The effect of a local application of fibroblast growth factor-2 on tendon-to-bone remodeling in rats with acute injury and repair of the supraspinatus tendon. J Shoulder Elbow Surg 2009;18:391-8.
20. Virchenko O, Grenegård M, Aspenberg P. Independent and additive stimulation of tendon repair by thrombin and platelets. Acta Orthop 2006;77:960-6.
21. Murray DH, Kubiak EN, Jazrawi LM, Araghi A, Kummer F, Loebenberg MI, et al. The effect of cartilage-derived mor- phogenetic protein 2 on initial healing of a rotator cuff defect in a rat model. J Shoulder Elbow Surg 2007;16:251-4.
22. Creaney L, Hamilton B. Growth factor delivery methods in the management of sports injuries: the state of play. Br J Sports Med 2008;42:314-20.
23. Kajikawa Y, Morihara T, Sakamoto H, Matsuda K, Oshima Y, Yoshida A, et al. Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing. J Cell Physiol 2008;215:837-45.
24. Virchenko O, Aspenberg P. How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimu- lation. Acta Orthop 2006;77:806-12.
25. Bedi A, Kovacevic D, Hettrich C, Gulotta LV, Ehteshami JR, Warren RF, et al. The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model. J Shoulder Elbow Surg 2010;19:384-91.
26. Bedi A, Fox AJ, Kovacevic D, Deng XH, Warren RF, Rodeo SA. Doxycycline-mediated inhibition of matrix metallopro- teinases improves healing after rotator cuff repair. Am J Sports Med 2010;38:308-17.
27. Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N. Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study. Disabil Rehabil 2008;30:1584-9.
28. Everts PA, Devilee RJ, Oosterbos CJ, Mahoney CB, Schattenkerk ME, Knape JT, et al. Autologous platelet gel and fibrin sealant enhance the efficacy of total knee arthro- plasty: improved range of motion, decreased length of stay and a reduced incidence of arthrofibrosis. Knee Surg Sports Traumatol Arthrosc 2007;15:888-94.
29. Tsay RC, Vo J, Burke A, Eisig SB, Lu HH, Landesberg R. Differential growth factor retention by platelet-rich plasma composites. J Oral Maxillofac Surg 2005;63:521-8.
30. 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;7:599-605.
31. Thomopoulos S, Soslowsky LJ, Flanagan CL, Tun S, Keefer CC, Mastaw J, et al. The effect of fibrin clot on healing rat supraspinatus tendon defects. J Shoulder Elbow Surg 2002;11: 239-47.