Comparison of the Effects of Platelet Rich Fibrin and Platelet Rich Plasma on Experimentally Induced Tendon Injury in Rabbits Treated with Methylprednisolone
Abstract
The aim of this study is to compare the effects of PRP and PRF on tendon injuries treated with methylprednisolone. In this context, the histopathological and immunohistochemical effects of PRP and PRF on tendon healing were evaluated. The study included 30 New Zealand rabbits (15 females and 15 males) with varying weights (1.5-3 kg) and ages (1-3 years). The experimental groups were designated as the steroid control group (Group B, n=10), the steroid+PRP group (Group C, n=10), and the steroid+PRF group (Group D, n=10). Additionally, the control tissues from a simultaneous study served as the empty control group (Group A). On the 14th postoperative day, a section encompassing the tenotomy site was excised from the area via incision. Healing was observed to be better in Groups C and D compared to Groups A and B. In Group A, inflammatory cell infiltration, primarily consisting of macrophages and polymorphonuclear leukocytes, along with a small number of lymphocytes and foreign-body giant cells, was higher than in all other groups. Group B exhibited less inflammatory cell infiltration compared to Group A. Additionally, hyperemia, hemorrhage, necrosis, new vessel formation, and fibroblasts of varying shapes and orientations were noted in Groups A and B. In contrast, cell infiltration was significantly lower in Groups C and D, while vascularization, fibroblast activity, and collagen density were higher. Collagen fibers were observed more regular bundles forms in Groups C and D compared to the control groups. The findings suggest that the combination of PRP or PRF with systemic methylprednisolone can effectively enhance tendon healing by modulating inflammatory responses, reducing adhesions, and supporting the formation of a well-organized extracellular matrix.
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Choukroun J, Diss A, Simonpieri A, Girard M-O, Schoeffler C, Dohan SL, Dohan AJJ, Mouhyi J, Dohan DM. Platelet-Rich Fibrin (PRF): A Second-Generation Platelet Concentrate. Part IV: Clinical Effects on Tissue Healing. Oral Surg.Oral Med. Oral Pathol. Oral Radiol. Endod. [Internet]. 2006; 101(3):e56–e60. doi: https://doi.org/dtqptc DOI: https://doi.org/10.1016/j.tripleo.2005.07.011
De Carli A, Lanzetti RM, Ciompi A, Lupariello D, Vadalà A, Argento G, Ferretti A, Vulpiani MC, Vetrano M. Can Platelet-Rich Plasma Have a Role in Achilles Tendon Surgical Repair? Knee Surg. Sports Traumatol. Arthrosc. [Internet]. 2016; 24(7):2231–2237. doi: https://doi.org/f8txx9 DOI: https://doi.org/10.1007/s00167-015-3580-1
Marx RE. Platelet-Rich Plasma (PRP): What Is PRP and What Is Not PRP?. Implant Dent. [Internet]. 2001; 10(4):225–228. doi: https://doi.org/c6x6mq DOI: https://doi.org/10.1097/00008505-200110000-00002
Berglund ME, Hart DA, Reno C, Wiig M. Growth Factor and Protease Expression during Different Phases of Healing after Rabbit Deep Flexor Tendon Repair. J. Orthop. Res. Off. Publ. Orthop. Res. Soc. [Internet]. 2011; 29(6):886–892. doi: https://doi.org/dtgg8q DOI: https://doi.org/10.1002/jor.21330
Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJJ, Mouhyi J, Gogly B. Platelet-Rich Fibrin (PRF): A Second-Generation Platelet Concentrate. Part I: Technological Concepts and Evolution. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. [Internet]. 2006; 101(3):e3744.doi: https://doi.org/cg8ngt DOI: https://doi.org/10.1016/j.tripleo.2005.07.008
Virchenko O, Grenegård M, Aspenberg P. Independent and Additive Stimulation of Tendon Repair by Thrombin and Platelets. Acta Orthop. [Internet]. 2006; 77(6):960–966. doi: https://doi.org/c4krrn DOI: https://doi.org/10.1080/17453670610013295
Aspenberg P, Virchenko O. Platelet Concentrate Injection Improves Achilles Tendon Repair in Rats. Acta Orthop. Scand. [Internet]. 2004; 75(1):93–99. doi: https://doi.org/fnhsj6 DOI: https://doi.org/10.1080/00016470410001708190
Kearney RS, Costa ML. Current Concepts in the Rehabilitation of an Acute Rupture of the Tendo Achillis. J. Bone Joint Surg. Br. [Internet]. 2012; 94(1):28–31. doi: https://doi.org/fxpvs7 DOI: https://doi.org/10.1302/0301-620X.94B1.28008
Parafioriti A, Armiraglio E, Del Bianco S, Tibalt E, Oliva F, Berardi AC. Single Injection of Platelet-Rich Plasma in a Rat Achilles Tendon Tear Model. Muscles Ligaments Tendons J. [Internet]. 2011; 1(2):41–47. PMID: 23738245. Avaliable in: https://goo.su/ghzwWF
Takamura M, Yasuda T, Nakano A, Shima H, Neo M. The Effect of Platelet-Rich Plasma on Achilles Tendon Healing in a Rabbit Model. Acta Orthop. Traumatol. Turc. [Internet]. 2017; 51(1):65. doi: https://doi.org/n49d DOI: https://doi.org/10.1016/j.aott.2016.12.001
Coombes BK, Bisset L, Vicenzino B. Efficacy and Safety of Corticosteroid Injections and Other Injections for Management of Tendinopathy: A Systematic Review of Randomised Controlled Trials. Lancet Lond. Engl. [Internet]. 2010; 376(9754):1751–1767. doi: https://doi.org/chs9bs DOI: https://doi.org/10.1016/S0140-6736(10)61160-9
Dean BJF, Lostis E, Oakley T, Rombach I, Morrey ME, Carr AJ. The Risks and Benefits of Glucocorticoid Treatment for Tendinopathy: A Systematic Review of the Effects of Local Glucocorticoid on Tendon. Semin. Arthritis Rheum. [Internet]. 2014; 43(4):570–576. doi: https://doi.org/f2pvh3 DOI: https://doi.org/10.1016/j.semarthrit.2013.08.006
Van Der Linden PD, Sturkenboom MCJM, Herings RMC, Leufkens HMG, Rowlands S, Stricker BHCh. Increased Risk of Achilles Tendon Rupture With Quinolone Antibacterial Use, Especially in Elderly Patients Taking Oral Corticosteroids. Arch. Intern. Med. [Internet]. 2003; 163(15):1801. doi: https://doi.org/cfz85b DOI: https://doi.org/10.1001/archinte.163.15.1801
Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJJ, Mouhyi J, Gogly B. Platelet-Rich Fibrin (PRF): A Second-Generation Platelet Concentrate. Part II: Platelet-Related Biologic Features. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. [Internet]. 2006; 101(3):e45–e50. doi: https://doi.org/fbsqc9 DOI: https://doi.org/10.1016/j.tripleo.2005.07.009
Kleinert HE, Schepel S, Gill T. Flexor tendon injuries. Surg. Clin. North. Am. [Internet]. 1981; 61(2):267–286. doi: https://doi.org/n49f DOI: https://doi.org/10.1016/S0039-6109(16)42381-9
Wong C-C, Huang Y-M, Chen C-H, Lin F-H, Yeh Y-Y, Bai M-Y. Cytokine and Growth Factor Delivery from Implanted Platelet-Rich Fibrin Enhances Rabbit Achilles Tendon Healing. Int. J. Mol. Sci. [Internet]. 2020; 21(9):3221. doi: https://doi.org/n49g DOI: https://doi.org/10.3390/ijms21093221
Bosch G, Moleman M, Barneveld A, van Weeren PR, van Schie HTM. The Effect of Platelet-Rich Plasma on the Neovascularization of Surgically Created Equine Superficial Digital Flexor Tendon Lesions. Scand. J. Med. Sci. Sports. [Internet]. 2011; 21(4):554–561. doi: https://doi.org/b95wcp DOI: https://doi.org/10.1111/j.1600-0838.2009.01070.x
Sen B, Güler S, Çeçen B, Kumtepe E, Bagriyanik A, Özkal S, Ali Özcan M, Özsan H, Sanli N, Tatari MH. The Effect of Autologous Platelet Rich Plasma in the Treatment of Achilles Tendon Ruptures: An Experimental Study on Rabbits. Balk. Med. J. [Internet]. 2016; 33(1):94–101. doi: https://doi.org/n49h DOI: https://doi.org/10.5152/balkanmedj.2015.15549
Dietrich F, L. Duré G, P. Klein C, F. Bampi V, V. Padoin A, D. Silva V, Braga-Silva J. Platelet-Rich Fibrin Promotes an Accelerated Healing of Achilles Tendon When Compared to Platelet-Rich Plasma in Rat. World J. Plast. Surg. [Internet]. 2015; 4(2):101–109. PMID: 26284178. Avaliable in: https://goo.su/5cKIERO
Liu X, Zhu B, Li Y, Liu X, Guo S, Wang C, Li S, Wang D. The Role of Vascular Endothelial Growth Factor in Tendon Healing. Front. Physiol. [Internet]. 2021; 12:766080. doi: https://doi.org/n49j DOI: https://doi.org/10.3389/fphys.2021.766080
Nakamura K, Kitaoka K, Tomita K. Effect of Eccentric Exercise on the Healing Process of Injured Patellar Tendon in Rats. J. Orthop. Sci. [Internet]. 2008; 13(4):371–378. doi: https://doi.org/bcxqpt DOI: https://doi.org/10.1007/s00776-008-1242-6
Chen CH, Cao Y, Wu YF, Bais AJ, Gao JS, Tang JB. Tendon Healing in Vivo: Gene Expression and Production of Multiple Growth Factors in Early Tendon Healing Period. J. Hand Surg. [Internet]. 2008; 33(10):1834–1842. doi: https://doi.org/d63tpf DOI: https://doi.org/10.1016/j.jhsa.2008.07.003
Sahin H, Tholema N, Petersen W, Raschke MJ, Stange R. Impaired Biomechanical Properties Correlate with Neoangiogenesis as Well as VEGF and MMP-3 Expression during Rat Patellar Tendon Healing. J. Orthop. Res. [Internet]. 2012; 30(12):1952–1957. doi: https://doi.org/f4czxx DOI: https://doi.org/10.1002/jor.22147
Stange R, Sahin H, Wieskötter B, Persigehl T, Ring J, Bremer C, Raschke MJ, Vieth V. In Vivo Monitoring of Angiogenesis during Tendon Repair: A Novel MRI-Based Technique in a Rat Patellar Tendon Model. Knee Surg. Sports Traumatol. Arthrosc. 2015; 23(8):2433–2439. doi: https://doi.org/f7kf9r DOI: https://doi.org/10.1007/s00167-014-2897-5
Hou Y, Mao Z, Wei X, Lin L, Chen L, Wang H, Fu X, Zhang J, Yu C. The Roles of TGF-Beta1 Gene Transfer on Collagen Formation during Achilles Tendon Healing. Biochem. Biophys. Res. Commun. [Internet]. 2009; 383(2):235–239. doi: https://doi.org/bjft8z DOI: https://doi.org/10.1016/j.bbrc.2009.03.159
Lyras DN, Kazakos K, Georgiadis G, Mazis G, Middleton R, Richards S, O’Connor D, Agrogiannis G. Does a Single Application of PRP Alter the Expression of IGF-I in the Early Phase of Tendon Healing? J. Foot Ankle Surg. [Internet]. 2011; 50(3);276–282. doi: https://doi.org/fbb9q3 DOI: https://doi.org/10.1053/j.jfas.2011.02.010
He P, Ruan D, Huang Z, Wang C, Xu Y, Cai H, Liu H, Fei Y, Heng BC, Chen W, Shen W. Comparison of Tendon Development Versus Tendon Healing and Regeneration. Front. Cell. Dev. Biol. [Internet]. 2022; 10:821667. doi: https://doi.org/n49k DOI: https://doi.org/10.3389/fcell.2022.821667
Tang JB, Wu YF, Cao Y, Chen CH, Zhou YL, Avanessian B, Shimada M, Wang XT, Liu PY. Basic FGF or VEGF Gene Therapy Corrects Insufficiency in the Intrinsic Healing Capacity of Tendons. Sci. Rep. [Internet]. 2016; 6:20643. doi: https://doi.org/f79mp3 DOI: https://doi.org/10.1038/srep20643
Lin J, Wang MX, Wei A, Zhu W, Murrell GA. The Cell Specific Temporal Expression of Nitric Oxide Synthase Isoforms during Achilles Tendon Healing. Inflamm. Res. [Internet]. 2001; 50(10):515–522. doi: https://doi.org/d9ww7d DOI: https://doi.org/10.1007/PL00000228
Bokhari AR, Murrell GAC. The Role of Nitric Oxide in Tendon Healing. J. Shoulder Elbow Surg. [Internet]. 2012; 21(2):238–244. doi: https://doi.org/fxtvh7 DOI: https://doi.org/10.1016/j.jse.2011.11.001
Murrell GAC. Using Nitric Oxide to Treat Tendinopathy. Br. J. Sports Med. [Internet]. 2007; 41(4):227. doi: https://doi.org/cphxpw DOI: https://doi.org/10.1136/bjsm.2006.034447
Doherty GP, Koike Y, Uhthoff HK, Lecompte M, Trudel G. Comparative Anatomy of Rabbit and Human Achilles Tendons with Magnetic Resonance and Ultrasound Imaging. Comp. Med. [Internet]. 2006; 56(1):68–74. PMID: 16521862. Avaliable in: https://goo.su/ReDgjU
Barbato KBG, Raposo C, Dias H, Paiva R, Costa J da, Rodriguez L, Almeida G de, Rocha-Barbosa O, Oliveira LP de, Carvalho J. Benefits of the Combined Use of NSAID and Early Exercise on Tendon Healing in a Murine Model. Open J. Anim. Sci. [Internet]. 2018; 8(4):357–369. doi: https://doi.org/n49m DOI: https://doi.org/10.4236/ojas.2018.84027
Blomgran P, Hammerman M, Aspenberg P. Systemic Corticosteroids Improve Tendon Healing When given after the Early Inflammatory Phase. Sci Rep. [Internet]. 2017; 7(1):12468. doi: https://doi.org/gb239w DOI: https://doi.org/10.1038/s41598-017-12657-0
Docheva D, Müller SA, Majewski M, Evans CH. Biologics for Tendon Repair. Adv. Drug Deliv. Rev. [Internet]. 2015; 84:222–239. doi: https://doi.org/f7dvqb DOI: https://doi.org/10.1016/j.addr.2014.11.015
Speed CA. Fortnightly Review: Corticosteroid Injections in Tendon Lesions. BMJ [Internet]. 2001; 323(7309):382–386. doi: https://doi.org/bkvfbx DOI: https://doi.org/10.1136/bmj.323.7309.382
Oxlund H. The Influence of a Local Injection of Cortisol onthe Mechanical Properties of Tendons and Ligaments and the Indirect Effect on Skin. Acta Orthop. Scand. [Internet]. 1980; 51(2):231–238. doi: https://doi.org/cg8bp8 DOI: https://doi.org/10.3109/17453678008990791
Beitzel K, McCarthy MB, Cote MP, Apostolakos J, Russell RP, Bradley J, ElAttrache NS, Romeo AA, Arciero RA, Mazzocca AD. The Effect of Ketorolac Tromethamine, Methylprednisolone, and Platelet-Rich Plasma on Human Chondrocyte and Tenocyte Viability. Arthrosc J. Arthrosc. Relat. Surg. [Internet]. 2013; 29(7):1164–1174. doi: https://doi.org/f2f34f DOI: https://doi.org/10.1016/j.arthro.2013.04.006
Tatari H, Kosay C, Baran O, Ozcan O, Ozer E. Deleterious Effects of Local Corticosteroid Injections on the Achilles Tendon of Rats. Arch. Orthop. Trauma Surg. [Internet]. 2001; 121(6):333–337. doi: https://doi.org/chgs4d DOI: https://doi.org/10.1007/s004020000236
Zargar Baboldashti N, Poulsen RC, Franklin SL, ThompsonMS, Hulley PA. Platelet-Rich Plasma Protects Tenocytes from Adverse Side Effects of Dexamethasone and Ciprofloxacin. Am. J. Sports Med. [Internet]. 2011; 39(9):1929–1935. doi: https://doi.org/fjx2nb DOI: https://doi.org/10.1177/0363546511407283
Zhang J, Keenan C, Wang JH-C. The Effects of Dexamethasone on Human Patellar Tendon Stem Cells: Implications for Dexamethasone Treatment of Tendon Injury. J. Orthop. Res. [Internet]. 2013; 31(1):105–110. doi: https://doi.org/n49n DOI: https://doi.org/10.1002/jor.22193
