DOI QR코드

DOI QR Code

Regenerative Injection Therapy on Tendon Healing: Dextrose Prolotherapy versus Platelet-Rich Plasma

  • Jungmin Lim (Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University) ;
  • Won-Jae Lee (Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University) ;
  • Min-Soo Seo (Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University) ;
  • Seong Mok Jeong (Department of Veterinary Surgery, College of Veterinary Medicine, Chungnam National University) ;
  • Sae-Kwang Ku (Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University) ;
  • Youngsam Kwon (Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University) ;
  • Sungho Yun (Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University)
  • Received : 2022.10.07
  • Accepted : 2023.03.20
  • Published : 2023.04.30

Abstract

The tendon is a dense connective tissue that connects muscle to bone and plays an essential role in joint motion. The injured tendon heals slowly owing to its low cellularity and vascularity. This study aimed to evaluate and compare the effects of regenerative injection therapy (RIT), 20 % dextrose prolotherapy (DP), and platelet-rich plasma (PRP) injections that can promote tendon healing. Twenty-one New Zealand white rabbits were divided into the control, DP, and PRP treatment groups. The superficial digital flexor tendon (SDFT) of the right hindlimb of each rabbit was used. A round defect of 2 mm was induced. Approximately 0.2 mL of 20% dextrose and autologous PRP were injected into the proximal and distal ends of the SDFT mass. Radiographic and ultrasonographic examination and cross-sectional area (CSA) calculations were performed pre-operatively and at 2, 4, and 8 weeks. The SDFT of both limbs was transected for biomechanical and histomorphometric evaluations. The SDFT of the left limb was transected for intact control. Semi-quantitative analysis was performed to evaluate the histomorphometric properties. Additional analysis was performed using H&E, Masson's trichrome, and immunohistochemical staining. The biomechanical evaluation showed that the treatment groups had higher tensile strength compared to the defect control group, while the PRP group had higher tensile strength than the DP group. On histological examination, the treatment groups appeared to be relatively closer to the remodeling phase of the healing process than the defect control group; the characteristics of the PRP group were closer to the remodeling phase than those of the DP group. The ultrasonographic examination showed different tendencies. Increased values in the CSA were observed during the early period in the treatment groups. This study suggests that PRP and DP can promote the healing of tendon injury, and these effects were superior with PRP than that with DP.

Keywords

References

  1. Allahverdi A, Sharifi D, Takhtfooladi MA, Hesaraki S, Khansari M, Dorbeh SS. Evaluation of low-level laser therapy, platelet-rich plasma, and their combination on the healing of Achilles tendon in rabbits. Lasers Med Sci 2015; 30: 1305-1313. https://doi.org/10.1007/s10103-015-1733-6
  2. Apaydin H, Bazancir Z, Altay Z. Injection therapy in patients with lateral epicondylalgia: hyaluronic acid or dextrose prolotherapy? A single-blind, randomized clinical trial. J Altern Complement Med 2020; 26: 1169-1175. https://doi.org/10.1089/acm.2020.0188
  3. Arias-Vazquez PI, Tovilla-Zarate CA, Legorreta-Ramirez BG, Burad Fonz W, Magana-Ricardez D, Gonzalez-Castro TB, et al. Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: systematic review of clinical trials. Adv Rheumatol 2019; 59: 39.
  4. Bagheri F, Tavasoly A, Dehghan MM, Sasani F, Raji M, Farzad Mohajeri S. Comparison of platelet-rich plasma (PRP), bone marrow-derived mesenchymal stem cells and their combination on the healing of Achilles tendon in rabbits. Iran J Vet Surg 2017; 12: 44-52.
  5. Bottagisio M, Lovati AB. A review on animal models and treatments for the reconstruction of Achilles and flexor tendons. J Mater Sci Mater Med 2017; 28: 45.
  6. Chen J, Yu Q, Wu B, Lin Z, Pavlos NJ, Xu J, et al. Autologous tenocyte therapy for experimental Achilles tendinopathy in a rabbit model. Tissue Eng Part A 2011; 17: 2037-2048. https://doi.org/10.1089/ten.tea.2010.0492
  7. DeChellis DM, Cortazzo MH. Regenerative medicine in the field of pain medicine: prolotherapy, platelet-rich plasma therapy, and stem cell therapy-theory and evidence. Tech Reg Anesth Pain Manag 2011; 15: 74-80. https://doi.org/10.1053/j.trap.2011.05.002
  8. Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: a review and author's perspective. J Cutan Aesthet Surg 2014; 7: 189-197. https://doi.org/10.4103/0974-2077.150734
  9. Ekwueme EC, Mohiuddin M, Yarborough JA, Brolinson PG, Docheva D, Fernandes HAM, et al. Prolotherapy induces an inflammatory response in human tenocytes in vitro. Clin Orthop Relat Res 2017; 475: 2117-2127. https://doi.org/10.1007/s11999-017-5370-1
  10. Gladstein B. A case for prolotherapy and its place in veterinary medicine. J Prolother 2012; 4: e870-e885.
  11. Gladstein B. Prolotherapy case studies from veterinarians. J Prolother 2010; 2: 323-326.
  12. Greenberg M. Pet prolotherapy: an overview and current case studies. J Prolother 2010; 2: 504-508.
  13. Guran S, Coban ZD, Karasimav O, Demirhan S, Karaagac N, Orscelik A, et al. Dextrose solution used for prolotherapy decreases cell viability and increases gene expressions of angiogenic and apopitotic factors. Gulhane Med J 2018; 60: 42-46. https://doi.org/10.26657/gulhane.00016
  14. Hackett GS. Ligament and tendon relaxation. Springfield: Charles C Thomas. 1958.
  15. He M, Gan AW, Lim AY, Goh JC, Hui JH, Chong AK. Bone marrow derived mesenchymal stem cell augmentation of rabbit flexor tendon healing. Hand Surg 2015; 20: 421-429. https://doi.org/10.1142/S0218810415500343
  16. James R, Kesturu G, Balian G, Chhabra AB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am 2008; 33: 102-112. https://doi.org/10.1016/j.jhsa.2007.09.007
  17. Kangas J, Pajala A, Siira P, Hamalainen M, Leppilahti J. Early functional treatment versus early immobilization in tension of the musculotendinous unit after Achilles rupture repair: a prospective, randomized, clinical study. J Trauma 2003; 54: 1171-1180; discussion 1180-1181. https://doi.org/10.1097/00005373-200306000-00026
  18. Kaux JF, Drion PV, Colige A, Pascon F, Libertiaux V, Hoffmann A, et al. Effects of platelet-rich plasma (PRP) on the healing of Achilles tendons of rats. Wound Repair Regen 2012; 20: 748-756. https://doi.org/10.1111/j.1524-475X.2012.00826.x
  19. Kim E, Lee JH. Autologous platelet-rich plasma versus dextrose prolotherapy for the treatment of chronic recalcitrant plantar fasciitis. PM R 2014; 6: 152-158. https://doi.org/10.1016/j.pmrj.2013.07.003
  20. Krapf D, Kaipel M, Majewski M. Structural and biomechanical characteristics after early mobilization in an Achilles tendon rupture model: operative versus nonoperative treatment. Orthopedics 2012; 35: e1383-e1388. https://doi.org/10.3928/01477447-20120822-26
  21. Lee AJ, Chung WH, Kim DH, Lee KP, Chung DJ, Do SH, et al. Anterior cruciate ligament reconstruction in a rabbit model using canine small intestinal submucosa and autologous platelet-rich plasma. J Surg Res 2012; 178: 206-215. https://doi.org/10.1016/j.jss.2012.01.052
  22. Leek BT, Tasto JP, Tibor LM, Healey RM, Freemont A, Linn MS, et al. Augmentation of tendon healing with butyric acid-impregnated sutures: biomechanical evaluation in a rabbit model. Am J Sports Med 2012; 40: 1762-1771. https://doi.org/10.1177/0363546512450691
  23. Lin CL, Huang CC, Huang SW. Effects of hypertonic dextrose injection in chronic supraspinatus tendinopathy of the shoulder: a randomized placebo-controlled trial. Eur J Phys Rehabil Med 2019; 55: 480-487. https://doi.org/10.23736/S1973-9087.18.05379-0
  24. Maffulli N, Longo UG, Loppini M, Spiezia F, Denaro V. New options in the management of tendinopathy. Open Access J Sports Med 2010; 1: 29-37. https://doi.org/10.2147/OAJSM.S7751
  25. Martins CA, Bertuzzi RT, Tisot RA, Michelin AF, do Prado JM, Stroher A, et al. Dextrose prolotherapy and corticosteroid injection into rat Achilles tendon. Knee Surg Sports Traumatol Arthrosc 2012; 20: 1895-1900. https://doi.org/10.1007/s00167-011-1789-1
  26. Maynard JA, Pedrini VA, Pedrini-Mille A, Romanus B, Ohlerking F. Morphological and biochemical effects of sodium morrhuate on tendons. J Orthop Res 1985; 3: 236-248. https://doi.org/10.1002/jor.1100030214
  27. Meier Burgisser G, Calcagni M, Bachmann E, Fessel G, Snedeker JG, Giovanoli P, et al. Rabbit Achilles tendon full transection model - wound healing, adhesion formation and biomechanics at 3, 6 and 12 weeks post-surgery. Biol Open 2016; 5: 1324-1333. https://doi.org/10.1242/bio.020644
  28. Morath O, Kubosch EJ, Taeymans J, Zwingmann J, Konstantinidis L, Sudkamp NP, et al. The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy-a systematic review including meta-analysis. Scand J Med Sci Sports 2018; 28: 4-15. https://doi.org/10.1111/sms.12898
  29. Moshiri A, Oryan A. Structural and functional modulation of early healing of full-thickness superficial digital flexor tendon rupture in rabbits by repeated subcutaneous administration of exogenous human recombinant basic fibroblast growth factor. J Foot Ankle Surg 2011; 50: 654-662. https://doi.org/10.1053/j.jfas.2011.05.002
  30. Movin T, Gad A, Reinholt FP, Rolf C. Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients. Acta Orthop Scand 1997; 68: 170-175.
  31. Oryan A, Moshiri A. A long term study on the role of exogenous human recombinant basic fibroblast growth factor on the superficial digital flexor tendon healing in rabbits. J Musculoskelet Neuronal Interact 2011; 11: 185-195.
  32. Oryan A, Moshiri A, Meimandi-Parizi AH. Short and long terms healing of the experimentally transverse sectioned tendon in rabbits. Sports Med Arthrosc Rehabil Ther Technol 2012; 4: 14.
  33. Oryan A, Moshiri A, Raayat AR. Novel application of Theranekron® enhanced the structural and functional performance of the tenotomized tendon in rabbits. Cells Tissues Organs 2012; 196: 442-455. https://doi.org/10.1159/000337860
  34. Parkinson J, Samiric T, Ilic MZ, Cook J, Handley CJ. Involvement of proteoglycans in tendinopathy. J Musculoskelet Neuronal Interact 2011; 11: 86-93.
  35. Pishgahi A, Abolhasan R, Shakouri SK, Soltani-Zangbar MS, Dareshiri S, Ranjbar Kiyakalayeh S, et al. Effect of dextrose prolotherapy, platelet rich plasma and autologous conditioned serum on knee osteoarthritis: a randomized clinical trial. Iran J Allergy Asthma Immunol 2020; 19: 243-252. https://doi.org/10.18502/ijaai.v19i3.3452
  36. Rabago D, Lee KS, Ryan M, Chourasia AO, Sesto ME, Zgierska A, et al. Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): results of a single-blind, pilot-level, randomized controlled trial. Am J Phys Med Rehabil 2013; 92: 587-596. https://doi.org/10.1097/PHM.0b013e31827d695f
  37. Sari A, Eroglu A. Comparison of ultrasound-guided platelet-rich plasma, prolotherapy, and corticosteroid injections in rotator cuff lesions. J Back Musculoskelet Rehabil 2020; 33: 387-396. https://doi.org/10.3233/BMR-191519
  38. Schwartz RG, Sagedy N. Prolotherapy: a literature review and retrospective study. J Neurol Orthop Med Surg 1991; 12: 220-223.
  39. Skalec A, Janeczek M, Czerski A. Anatomy and histology of the rabbit common calcanean tendon. Anat Histol Embryol 2019; 48: 466-475. https://doi.org/10.1111/ahe.12468
  40. Stoll C, John T, Conrad C, Lohan A, Hondke S, Ertel W, et al. Healing parameters in a rabbit partial tendon defect following tenocyte/biomaterial implantation. Biomaterials 2011; 32: 4806-4815. https://doi.org/10.1016/j.biomaterials.2011.03.026
  41. Taylor DW, Petrera M, Hendry M, Theodoropoulos JS. A systematic review of the use of platelet-rich plasma in sports medicine as a new treatment for tendon and ligament injuries. Clin J Sport Med 2011; 21: 344-352. https://doi.org/10.1097/JSM.0b013e31821d0f65
  42. Thermann H, Frerichs O, Biewener A, Krettek C. Healing of the Achilles tendon: an experimental study. Foot Ankle Int 2001; 22: 478-483. https://doi.org/10.1177/107110070102200604
  43. Tohidnezhad M, Varoga D, Wruck CJ, Brandenburg LO, Seekamp A, Shakibaei M, et al. Platelet-released growth factors can accelerate tenocyte proliferation and activate the anti-oxidant response element. Histochem Cell Biol 2011; 135: 453-460. https://doi.org/10.1007/s00418-011-0808-0
  44. Wu F, Nerlich M, Docheva D. Tendon injuries: basic science and new repair proposals. EFORT Open Rev 2017; 2: 332-342. https://doi.org/10.1302/2058-5241.2.160075
  45. Yelland MJ, Sweeting KR, Lyftogt JA, Ng SK, Scuffham PA, Evans KA. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial. Br J Sports Med 2011; 45: 421-428. https://doi.org/10.1136/bjsm.2009.057968