Modern aspects of the use of plasma enriched in soluble platelet factors in the treatment of injuries and diseases of the musculoskeletal system

The review of literature presents the new direction in the treatment of sports injuries and diseases of the musculoskeletal system – using of autologous platelet-rich plasma/plasma enriched in soluble platelet factors (PRP/PORFT). PRP/PORFT reveals anti-inflammatory, analgesic, anticatabolic and regenerative effects after local injection to affected area. Technology of preparation and clinical application of PRP/PORFT were under consideration. There were described the results of clinical studies on PRP/PORFT application in sports medicine and damage of musculoskeletal system. It was shown the clinical efficacy of 2-3 injections of PRP/PORFT into the area of muscle, ligaments, joints injury. Most effective use of PRP/PORFT was shown for therapy of lateral epicondylitis and osteoarthritis. There were no yet evidences for its efficacy in therapy of patients with damaged Achilles tendon. The best clinical effects of PRP/PORFT use was demonstrated in patients with trauma and damage of musculoskeletal system at the initial stages of treatment, and also as a part of rehabilitation courses.

1. Andia I, Maffulli N. How far have biological therapies come in regenerative sport medicine? Expert Opinion on Biological therapy. 2018;18(7):785-793.

2. Yang A, Hunter CW, McJunkin TL. PRP therapies (tendons, joints, spine). Deer’s treatment of pain. Springer Nature Switzerland AG. 2019;91:749-756.

3. Zhu Y, Yuan M, Meng HY, Wang AY, Guo QY, Wang Y, Peng J. Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review. Osteoarthritis and cartilage. 2013;21:1627-1637.

4. Milants C, Bruyere O, Kaux J-F. Responders to platelet-rich plasma in osteoargtritis: a technical analysis. BioMed Research International. 2017;(1):1-11. DOI:10.1155/2017/7538604

5. Cook CS, Smith PA. Clinical update: why PRP should be your first choice for injection therapy in treating osteoarthritis of the knee. Current Reviews in Musculosceletal Medicine. 2018;11: 583-592.

6. Rossi LA, Romoli ARM, Altieri BAB, Flor JAB, Scordo WE, Elizondo CM. Does Platelet-rich plasma decrease time to return to sports in acute muscle tear? A randomized controlled trial. Knee Surgery, Sports Traumatology, Arthroscopy. 2017;25:3319-3325.

7. Setayesh K, Villarreal A, Gottschalk A, Tokish JM, Choate WS. Treatment of muscle injuries with platelet-rich plasma: a review of the literature. Current Reviews in Musculosceletal Medicine. 2018;11:636-642.

8. Bisciotti GN, Volpi P, Amato M, Alberti G, Allegra F, Aprato A, Aptina M, Auci A, Bait C, Bastieri GM, Balzarini L, Belli A, Bellini G, Bettinsoli P, Bisciotti A, Bisciotti A, Bona S, Brambilla L, Bresciani M. Italian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athlete. BMJ Open Sport & Exercise Medicine. 2018;4:e000323.

9. Zagorodny GM, Mucha PG, Yasyukevich AS, Gulevich NP. Otechestvennyy i zarubezhnyy opyt primeneniya PRP-terapii v meditsine i sportivnoy praktike (obzor literatury). Prikladnaya sportivnaya nauka. 2017;1(5):83-91. Russian.

10. Cugat R, Cusco X, Srijas R, Barastegui D, Alvarez-Diaz P, Alentorn-Geli E, Rius M, Steinbacher G, Sala E, Boffa JJ, Grossi S, Garcia-Balletbo M, Tizol S, Laiz P. PRGF on sport-related ligament injuries. Platelet rich plasma in orthopaedics and sports medicine. Springer International Publishing AG, part of Springer Nature. 2018;10:175-188.

11. Achkasov EE, Litvinenko AS, Kurshev VV. Shockwave therapy in diseases and injuries of the musculoskeletal system due sports. Bulletin of rehabilitation medicine. 2015;1(65):42-50. Russian.

12. Tsykunov MB. The effectiveness of training with biological feedback for damage capsular-ligament structures of the knee joint. Bulletin of rehabilitation medicine. 2018;4(86):29-33. Russian.

13. Piuzzi NS, Dominici M, Long M, Pascual-Garrido C, Rodeo S, Huard J, Guicheux J, McFarland R, Goodrich LR, Maddens S, Robey PG, Bauer TW, Barrett J, Barry F, Karli D, Chu CR, Weiss DJ, Martin I, Jorgensen C, Muschler GF. Proceedings of the signature series symposium «cellular therapies for orthopaedics and musculoskeletal disease proven and unproven therapies – promise, facts and fantasy», international society for cellular therapies, Montreal Canada, May 2, 2018. Cytotherapy. 2018;20:1381-1400.

14. Sanchez M, Azofra J, Anitua E, Andia I, Padilla S, Santisteban J, Mujika I. Plasma rich in growth factors to treat an articular cartilage avulsion: a case report. Medicine & Science in Sports & Exercise. 2003;35:1648-1652.

15. Scully D, Matsakas A. Current insight into the potential misuse of platelet-based applications for doping in sports. International Journal of Sports Medicine. 2019;40:427-433.

16. Andia I, Abate M. Platelet-rich plasma: underlying biology and clinical correlates. Regenerative Medicine. 2013;8(5):645-658.

17. Potapnev MP, Arabey AA, Kondratenko GG, Troyanov AA, Kosmacheva SM, Ihnatsenko SI, Kakhno AA, Danilkovich NN, Krivenko SI, Nazarova EA, Levandovskaya OV, Kopetski IS, Loginov VV. Soluble preparations of platelet growth factors and their medical implementation Zdravookhraneniye (Minsk) (Healthcare). 2014;9:32-40. Russian.

18. Renn TY, Kao YH, Wang CC, Burnouf T. Anti-inflammatory effects of platelet biomaterials in a macrophage cellular model. Vox Sanguinus. 2015;109(2):138-147.

19. Navani A, Li G, Chrystal J. Platelet rich plasma in musculoskeletal pathology: a necessary rescue or a lost cause? Pain Physician. 2017;20:345-356.

20. Gain YM, Gerasimenko MA, Shakhray SV, Hrischanovich VY, Bogdan VG, Bordakov PV, Gain MY. Possibilities and prospects of platelet rich plasma in surgery and medicine. Innovative technologies in medicine. 2017;5(3):104-124. Russian.

21. Lana JF, Huber SC, Purita J, Tambeli CH, Santos GS, Paulus C, Annichino-Bizzachi JM. Leukocyte-rich PRP versus Leukocyte-poor PRP - The role of monocyte/macrophage function in the healing cascade. Journal of Clinical Orthopaedics and Trauma. 2013;13;10(1):S7-S12. DOI:10.1016/jjcot.2019.05.008

22. Chelini F, Tani A, Zecchi-Orlandini S, Sassoli C. Influence of platelet-rich and platelet-poor plasma on endogenous mechanisms of skeletal muscle repair/regeneration. International Journal of Molecular Science. 2019;20:683.

23. Khoshbin A, Leroux T, Wasserstein D, Mark P, Theodoropoulos J, Ogilvie-Harris D, Gandhi R, Takhar K, Kin B, Lum G, Chahal J. The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systemic review with quantitative synthesis. Arthroscopy. The Journal of Arthroscopic and Related Surgery. 2013;29(12):2037-2048.

24. O’Connel B, Wragg NM, Wilson SL. The use of PRP injections in the management of knee osteoarthritis. Cell and Tissue Research. 2019;376:143-152.

25. Saclier M, Cuvellier S, Magnan M, Mounier R, Chazaud B. Monocyte/macrophage interactions with myogenic precursor cells during skeletal muscle regeneration. FEBS Journal. 2013;280: 4118-4130.

26. Stratos I, Mittlmeier T. Muscle, ligament and tendon regeneration. In book: Regenerative Medicine – from protocol to patient. Springer Int. Publ. Switzerland. 2016;11:349-366. DOI: 10.1007/978-3-319-28386-9_11

27. Andia I, Latorre PM, Gomez MC, Burgos-Alonso N, Abate M, Maffulli N. Platelet-rich plasma in the conservative treatment of painful tendinopathy: a systemic review and meta-analysis of controlled studies. British Medical Bulletin. 2014;110:99-115.

28. Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation of osteoarthritis. Nature Reviews. Rheumatology. 2013;9:721-730.

29. Potapnev MP, Krivenko SI, Bogdan VG, Kosmacheva SM, Shlyaga OL, Karpenko FN. Platelet-rich derived plasma: manufacture and medical application. Zdravookhraneniye (Minsk) (Healthcare). 2018;10(859):38-44. Russian.

30. Gholami M, Ravaghi H, Salehi M, Yekta AA, Doaee S, Jaafaripooyan E. A systemic review and meta-analysis of the application of platelet-rich plasma in sports medicine. Electronic Physician. 2016;8(5):2325-2332.

31. Piccin A, Di Pierro AM, Canzian L, Primerano M, Corvetta D, Negri G, Mazzoleni G, Gastl G, Steurer M, Gentilini I, Eisendle K, Fontanella F. Platelet gel: a new therapeutic tool with great potential. Blood Transfusion. 2017;15:333-340.

32. Cohn CS, Lockhart E, McCullough JJ. The use of autologous platelet-rich plasma in the orthopedic setting. Transfusion. 2015;55:1812-1820.

33. Hamid MSA, Ali MRM, Yusof A, George J, Lee LPC. Platelet-rich plasma injections for the treatment of hamstring injuries: a randomized controlled trial. The American Journal of Sports Medicine. 2014;42(10):2410-2418.

34. Scott A, La Prade RF, Harmon KG, Filardo G, Kon E, Della Villa S, Bahr R, Moksnes H, Torgalsen T, Lee J, Dragoo JL, Engebretsen L. Platelet-rich plasma for patellar tendinopathy. A randomized controlled trial of leukocyte-rich PRP or leukocyte-poor PRP versus saline. The American Journal of Sports Medicine. 2019;47(7):1654-1661.

35. Gato-Calvo L, Magalhaes J, Ruiz-Romero C, Blanco FJ, Burguera EF. Platelet-rich plasma: review of current evidence. Therapeutic Advances in Chronic Disease. 2019;10:1-18.

36. Strunk D, Lozano M, Marks DC, Loh YS, Gstraunthaler G, Schennach H, Rohde E, Laner-Plamberger S, Oller M, Nystedt J, Lotfi R, Rojewski M, Schrezenmeier H, Bieback K, Schafer R, Bakchout T, Waidmann M, Jonsdottir-Buch SM, Montazeri H, Sigurjonsson OE, Iudicone P, Fioravanti D, Pierelli L, Introna M, Capelli C, Falanga A, Takanishi M, Lopez-Villar O, Burnouf T, Reems JA, Pierce J, Prestal AM, Schallmoser K. International forum on GMP-grade human platelet lysate for cell propagation: summary. Vox Sanguinus. 2018;113:80-87.

37. Bubnov R, Yevseenko V, Semeniv I. Ultrasound guided injections of platelet rich plasma for muscle injury in professional athletes. Comparative study. Medical Ultrasonography. 2013;15(2): 101-105.

38. Medvedev AV, Kholodkova OL, Borysova OV, Bahchevan OL. The effectiveness of platelet-rich plasma (PRP) administration in professional football players’ muscle injuries. Galits'kiy likarskiy visnik. 2015;22(3):29-33. http://nbuv.gov.ua/UJRN/glv_2015_22_3%282%29__12 Ukrainian

39. Bernuzzi G, Petraglia F, Pedrini MF, De Filippo M, Pogliacomi F, Verdano MA, Costantino C. Use of platelet-rich plasma in the care of sports injuries: our experience with ultrasoundguided injection. Blood Transfusion. 2014;12(1):229-234.

40. Borrione P, Fossati C, Pereira MT, Giannini S, Davico M, Minganti C, Pigozzi F. The use of platelet-rich plasma (PRP) in the treatment of gastrocnemius strains: a retrospective observational study. Platelets. 2018;29(6):596-601.

41. Aprili G, Gandini G, Guaschino R, Mazzucco L, Salvaneschi L, Vaglio S.SIMTI recommendations on blood components for non-transfusional use. Blood Transfusion. 2013;11(4):611-622.

42. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. The American Journal of Sports Medicine. 2006;34(11):1774-1778.

43. Gosens T, Peerbooms JC, van Laar W, den Oudsten BL. Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis. A double-blind randomized controlled trial with 2-year follow-up. The American Journal of Sports Medicine. 2011;39(6):1200-1208.

44. Omar AS, Ibrahim ME, Ahmed AS, Said M. Local injection of autologous platelet rich plasma and corticosteroid in treatment of lateral epicondylitis and plantar fasciitis: randomized clinical trial. The Egyptian Rheumatologist. 2012;34(2):43-49.

45. Abate M, Di Carlo L, Salini V. Platelet-rich plasma diffusion in Achilles tendon: relationship with therapeutic outcomes. Medical Principles and Practice. 2019;28:367-372.

46. McCrum CL, Costello J, Onishi K, Stewart C, Vyas D. Return to play after PRP and rehabilitation of 3 elite ice hockey players with ulnar collateral ligament injuries of the elbow. The Orthopaedic Journal of Sports Medicine. 2018;6(8):2325967118790760.

47. Sanli I, Morgan B, van Tilborg F, Funk L, Gosens T. Single injection of platelet-rich plasma (PRP) for the treatment of refractory distal biceps tendonitis: long-term results of a prospective multicenter cohort study. Knee Surgery, Sports Traumatology, Arthroscopy. 2016;24(7):2308-2312.

48. Wesner M, Defreitas T, Bredy H, Pothier L, Qin Z, McKillop B, Gross DP. A pilot study evaluating the effectiveness of plateletrich plasma therapy for treating degenerative tendinopathies: a randomized control trial with synchronous observational cohor. PLOSone. 2016;11(2):e0147842.

49. Bashkina AS, Shirokova LYu, Khyazeva TS, Parulya OM, Abrosimova EV, Naskov SM. Application of platelet-rich plasma in reduction of greater trochanteric pain syndrome. Traumatology and Orthopedics of Russia. 2011;2(60):57-61. Russian.

50. Baltzer AWA, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment of knee osteoarthritis. Osteoarthritis and Cartilage. 2009;17:152-160.

51. Nikolaev VI, Chernyakova YuM, Pinchuk LS, Linkevich ER, Beloenko ED. Lokalnaya terapiya gonartroza autosyvorotkoy krovi patsiyenta. Proceedings of the National Academy of Sciences of Belarus. Medical Series. 2006;4:50-53. Russian.

52. Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenaсchi A, Fornasari PM, Giannini S, Marcacci M. Plateletrich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy. 2011;19:528-535.

53. Mastykau AN, Deykalo VP, Balaboshka KB. Obogashchennaya trombotsitami plazma v lechenii postravmaticheskoy khondropatii kolennogo sustava. Novosti khirurgii. 2012; 20(5):77- 81. Russian.

54. Shirokova LYu, Noskov SM, Bakhtiarova TI, Shigiryova AV, Noskova TS. Lokalnaya terapiya gonartroza autologichnoy obogashchennoy trombotsitami plazmy. Modern Technologies in Medicine. 2012;(1):97-100. Russian.

55. Su K, Bai Y, Wang J, Zhang H, Liu H, Ma S. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous injections to treat patients with knee osteoarthritis. Clinical Rheumatology. 2018;37(5): 1341-1350.

56. Glynn LG, Mustafa A, Casey M, Krawczyk J, Bloom J, Galvin R, Hannigan A, Dunne CP, Murphy AW, Mallen C. Platelet-rich plasma (PRP) therapy for knee arthritis: a feasibility study in primary care. Pilot and Feasibility Studies. 2019;4:93.

57. Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JK. Intraarticular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: a randomized, double-blind, triple-parallel, placebocontrolled clinical trial. Arthroscopy: The Journal of Arthroscopic and Related Surgery. 2019;35(1):106-117.

58. Guillibert C, Charpin C, Raffray M, Benmenni A, Dehaut F-X, El Ghobeira G, Giogi R, Magalon J, Arniaud D. Single injection of high volume of autologous pure PRP provides a significant improvement in knee osteoarthritis: a prospective routine care study. International Journal of Molecular Science. 2019;20:1327.

59. Bottegoni C, Dei Giudici L, Salvemini S, Chiurazzi E, Bencivenga R, Gigante A. Homologous platelet-rich plasma for the treatment of knee osteoarthritis in selected elderly patients: an open-label, uncontrolled, pilot study. Therapeutic Advances in Musculoskeletal Disease. 2016;8(2):35-41.