J Korean Foot Ankle Soc.  2023 Sep;27(3):79-86. 10.14193/jkfas.2023.27.3.79.

Hyaluronic Acid and Platelet-Rich Plasma Injections in Foot and Ankle Disorders

• Lee GW
• Kang J

• KMID: 2545985
• DOI: http://doi.org/10.14193/jkfas.2023.27.3.79

Abstract

Numerous nonoperative treatments have been used to reduce pain and improve the clinical outcomes of patients with foot and ankle disorders. Among these treatments, hyaluronic acid and platelet-rich plasma (PRP) injections have been used increasingly. This review analyzes the recent literature reporting the efficacy and indications for hyaluronic acid and PRP injections. Hyaluronic acid and PRP can be used safely as adjuncts. Hyaluronic acid injections have shown efficacy and have a promising role as an adjuvant treatment method. In addition, its indication has expanded to various foot and ankle diseases over osteoarthritis. On the other hand, the efficacy of PRP injection has not yet been clarified, and the lack of standardization of procedures for the preparation and administration of PRP makes it difficult to establish definitive treatment indications.

Keyword

Hyaluronic acid; Platelet-rich plasma; Injection; Foot; Ankle

Reference

1. Keene DJ, Alsousou J, Harrison P, O'Connor HM, Wagland S, Dutton SJ, et al. PATH-2 Trial group. Platelet-rich plasma injection for acute Achilles tendon rupture : two-year follow-up of the PATH-2 randomized, placebo-controlled, superiority trial. Bone Joint J. 2022; 104-B:1256–65. doi: 10.1302/0301-620X.104B11.BJJ-2022-0653.R1. DOI: 10.1302/0301-620X.104B11.BJJ-2022-0653.R1. PMID: 36317349. PMCID: PMC9621093.

2. Lee GW, Kwak WK, Lee KB. 2022; Effects and safety of intra-articular sodium hyaluronate injection for the treatment of ankle osteoarthritis: a prospective clinical trial. J Foot Ankle Surg. 61:345–9. doi: 10.1053/j.jfas.2021.09.012. DOI: 10.1053/j.jfas.2021.09.012. PMID: 34801379.

3. Song HH. 2021; How effective is the injection therapy in foot and ankle disorder? J Korean Foot Ankle Soc. 25:10–6. doi: 10.14193/jkfas.2021.25.1.10. DOI: 10.14193/jkfas.2021.25.1.10.

4. Le ADK, Enweze L, DeBaun MR, Dragoo JL. 2018; Current clinical recommendations for use of platelet-rich plasma. Curr Rev Musculoskelet Med. 11:624–34. doi: 10.1007/s12178-018-9527-7. DOI: 10.1007/s12178-018-9527-7. PMID: 30353479. PMCID: PMC6220007.

5. Padilla S, Sánchez M, Vaquerizo V, Malanga GA, Fiz N, Azofra J, et al. 2021; Platelet-rich plasma applications for Achilles tendon repair: a bridge between biology and surgery. Int J Mol Sci. 22:824. doi: 10.3390/ijms22020824. DOI: 10.3390/ijms22020824. PMID: 33467646. PMCID: PMC7830415.

6. Shang XL, Tao HY, Chen SY, Li YX, Hua YH. 2016; Clinical and MRI outcomes of HA injection following arthroscopic microfracture for osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc. 24:1243–9. doi: 10.1007/s00167-015-3575-y. DOI: 10.1007/s00167-015-3575-y. PMID: 25763853.

7. Creamer P, Hochberg MC. 1997; Osteoarthritis. Lancet. 350:503–8. doi: 10.1016/S0140-6736(97)07226-7. DOI: 10.1016/S0140-6736(97)07226-7. PMID: 9274595. PMCID: PMC10477960.

8. Witteveen AG, Hofstad CJ, Kerkhoffs GM. 2015; Hyaluronic acid and other conservative treatment options for osteoarthritis of the ankle. Cochrane Database Syst Rev. 2015:CD010643. doi: 10.1002/14651858.CD010643.pub2. DOI: 10.1002/14651858.CD010643.pub2. PMID: 26475434. PMCID: PMC9254328.

9. Testa G, Giardina SMC, Culmone A, Vescio A, Turchetta M, Cannavò S, et al. 2021; Intra-articular injections in knee osteoarthritis: a review of literature. J Funct Morphol Kinesiol. 6:15. doi: 10.3390/jfmk6010015. DOI: 10.3390/jfmk6010015. PMID: 33546408. PMCID: PMC7931012.

10. Chang WH, Liu PY, Lin MH, Lu CJ, Chou HY, Nian CY, et al. 2021; Applications of hyaluronic acid in ophthalmology and contact lenses. Molecules. 26:2485. doi: 10.3390/molecules26092485. DOI: 10.3390/molecules26092485. PMID: 33923222. PMCID: PMC8123179.

11. Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. 2015; The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 16:321. doi: 10.1186/s12891-015-0775-z. DOI: 10.1186/s12891-015-0775-z. PMID: 26503103. PMCID: PMC4621876.

12. de Oliveira JD, Carvalho LS, Gomes AM, Queiroz LR, Magalhães BS, Parachin NS. 2016; Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms. Microb Cell Fact. 15:119. doi: 10.1186/s12934-016-0517-4. DOI: 10.1186/s12934-016-0517-4. PMID: 27370777. PMCID: PMC4930576.

13. Nicholls M, Manjoo A, Shaw P, Niazi F, Rosen J. 2018; A comparison between rheological properties of intra-articular hyaluronic acid preparations and reported human synovial fluid. Adv Ther. 35:523–30. doi: 10.1007/s12325-018-0688-y. DOI: 10.1007/s12325-018-0688-y. PMID: 29542009. PMCID: PMC5910459.

14. Hummer CD, Angst F, Ngai W, Whittington C, Yoon SS, Duarte L, et al. 2020; High molecular weight Intraarticular hyaluronic acid for the treatment of knee osteoarthritis: a network meta-analysis. BMC Musculoskelet Disord. 21:702. doi: 10.1186/s12891-020-03729-w. DOI: 10.1186/s12891-020-03729-w. PMID: 33097031. PMCID: PMC7585216.

15. Younger ASE, Penner M, Wing K, Veljkovic A, Nacht J, Wang Z, et al. 2019; Nonanimal hyaluronic acid for the treatment of ankle osteoarthritis: a prospective, single-arm cohort study. J Foot Ankle Surg. 58:514–8. doi: 10.1053/j.jfas.2018.10.003. DOI: 10.1053/j.jfas.2018.10.003. PMID: 30910489.

16. Jantzen C, Ebskov LB, Andersen KH, Benyahia M, Rasmussen PB, Johansen JK. 2020; The effect of a single hyaluronic acid injection in ankle arthritis: a prospective cohort study. J Foot Ankle Surg. 59:961–3. doi: 10.1053/j.jfas.2020.03.015. DOI: 10.1053/j.jfas.2020.03.015. PMID: 32475656.

17. Murphy EP, Curtin M, McGoldrick NP, Thong G, Kearns SR. 2017; Prospective evaluation of intra-articular sodium hyaluronate injection in the ankle. J Foot Ankle Surg. 56:327–31. doi: 10.1053/j.jfas.2016.09.017. DOI: 10.1053/j.jfas.2016.09.017. PMID: 28117254.

18. Cohen MM, Altman RD, Hollstrom R, Hollstrom C, Sun C, Gipson B. 2008; Safety and efficacy of intra-articular sodium hyaluronate (Hyalgan) in a randomized, double-blind study for osteoarthritis of the ankle. Foot Ankle Int. 29:657–63. doi: 10.3113/FAI.2008.0657. DOI: 10.3113/FAI.2008.0657. PMID: 18785414.

19. Sun SF, Hsu CW, Sun HP, Chou YJ, Li HJ, Wang JL. 2011; The effect of three weekly intra-articular injections of hyaluronate on pain, function, and balance in patients with unilateral ankle arthritis. J Bone Joint Surg Am. 93:1720–6. doi: 10.2106/JBJS.J.00315. DOI: 10.2106/JBJS.J.00315. PMID: 21938376.

20. Luciani D, Cadossi M, Tesei F, Chiarello E, Giannini S. 2008; Viscosupplementation for grade II osteoarthritis of the ankle: a prospective study at 18 months' follow-up. Chir Organi Mov. 92:155–60. doi: 10.1007/s12306-008-0066-z. DOI: 10.1007/s12306-008-0066-z. PMID: 19067120.

21. Mei-Dan O, Kish B, Shabat S, Masarawa S, Shteren A, Mann G, et al. 2010; Treatment of osteoarthritis of the ankle by intra-articular injections of hyaluronic acid: a prospective study. J Am Podiatr Med Assoc. 100:93–100. DOI: 10.7547/1000093. PMID: 20237359.

22. Bhandari M, Bannuru RR, Babins EM, Martel-Pelletier J, Khan M, Raynauld JP, et al. 2017; Intra-articular hyaluronic acid in the treatment of knee osteoarthritis: a Canadian evidence-based perspective. Ther Adv Musculoskelet Dis. 9:231–46. doi: 10.1177/1759720X17729641. Erratum in: Ther Adv Musculoskelet Dis. 2017;9:295. DOI: 10.1177/1759720X17729641. PMID: 28932293. PMCID: PMC5600311.

23. Legré-Boyer V. 2015; Viscosupplementation: techniques, indications, results. Orthop Traumatol Surg Res. 101(1 Suppl):S101–8. doi: 10.1016/j.otsr.2014.07.027. DOI: 10.1016/j.otsr.2014.07.027. PMID: 25596987.

24. Johnson JE, Klein SE, Putnam RM. 2011; Corticosteroid injections in the treatment of foot & ankle disorders: an AOFAS survey. Foot Ankle Int. 32:394–9. doi: 10.3113/FAI.2011.0394. DOI: 10.3113/FAI.2011.0394. PMID: 21733442.

25. Nishida Y, Kano K, Nobuoka Y, Seo T. 2021; Sustained-release diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate) for knee osteoarthritis: a randomized phase 2 study. Rheumatology (Oxford). 60:1435–44. doi: 10.1093/rheumatology/keaa605. DOI: 10.1093/rheumatology/keaa605. PMID: 33006602. PMCID: PMC7937021.

26. Kubo T, Kumai T, Ikegami H, Kano K, Nishii M, Seo T. 2022; Diclofenac-hyaluronate conjugate (diclofenac etalhyaluronate) intra-articular injection for hip, ankle, shoulder, and elbow osteoarthritis: a randomized controlled trial. BMC Musculoskelet Disord. 23:371. doi: 10.1186/s12891-022-05328-3. DOI: 10.1186/s12891-022-05328-3. PMID: 35443676. PMCID: PMC9022275.

27. Osti L, Berardocco M, di Giacomo V, Di Bernardo G, Oliva F, Berardi AC. 2015; Hyaluronic acid increases tendon derived cell viability and collagen type I expression in vitro: comparative study of four different Hyaluronic acid preparations by molecular weight. BMC Musculoskelet Disord. 16:284. doi: 10.1186/s12891-015-0735-7. Erratum in: BMC Musculoskelet Disord. 2015;16:334. DOI: 10.1186/s12891-015-0735-7. PMID: 26444018. PMCID: PMC4596363.

28. Dilley JE, Everhart JS, Klitzman RG. 2022; Hyaluronic acid as an adjunct to microfracture in the treatment of osteochondral lesions of the talus: a systematic review of randomized controlled trials. BMC Musculoskelet Disord. 23:313. doi: 10.1186/s12891-022-05236-6. DOI: 10.1186/s12891-022-05236-6. PMID: 35366851. PMCID: PMC8976295.

29. Boffa A, Previtali D, Di Laura Frattura G, Vannini F, Candrian C, Filardo G. 2021; Evidence on ankle injections for osteochondral lesions and osteoarthritis: a systematic review and meta-analysis. Int Orthop. 45:509–23. doi: 10.1007/s00264-020-04689-5. DOI: 10.1007/s00264-020-04689-5. PMID: 32647968.

30. Hwang YG, Lee JW, Park KH, Hsienhao C, Han SH. 2020; Intra-articular injections of hyaluronic acid on osteochondral lesions of the talus after failed arthroscopic bone marrow stimulation. Foot Ankle Int. 41:1376–82. doi: 10.1177/1071100720945944. DOI: 10.1177/1071100720945944. PMID: 32844669.

31. Doral MN, Bilge O, Batmaz G, Donmez G, Turhan E, Demirel M, et al. 2012; Treatment of osteochondral lesions of the talus with microfracture technique and postoperative hyaluronan injection. Knee Surg Sports Traumatol Arthrosc. 20:1398–403. doi: 10.1007/s00167-011-1856-7. DOI: 10.1007/s00167-011-1856-7. PMID: 22205098.

32. Mei-Dan O, Carmont MR, Laver L, Mann G, Maffulli N, Nyska M. 2012; Platelet-rich plasma or hyaluronate in the management of osteochondral lesions of the talus. Am J Sports Med. 40:534–41. doi: 10.1177/0363546511431238. DOI: 10.1177/0363546511431238. PMID: 22253252.

33. Oliva F, Marsilio E, Asparago G, Frizziero A, Berardi AC, Maffulli N. 2021; The impact of hyaluronic acid on tendon physiology and its clinical application in tendinopathies. Cells. 10:3081. doi: 10.3390/cells10113081. DOI: 10.3390/cells10113081. PMID: 34831304. PMCID: PMC8625461.

34. Kumai T, Muneta T, Tsuchiya A, Shiraishi M, Ishizaki Y, Sugimoto K, et al. 2014; The short-term effect after a single injection of high-molecular-weight hyaluronic acid in patients with enthesopathies (lateral epicondylitis, patellar tendinopathy, insertional Achilles tendinopathy, and plantar fasciitis): a preliminary study. J Orthop Sci. 19:603–11. doi: 10.1007/s00776-014-0579-2. DOI: 10.1007/s00776-014-0579-2. PMID: 24817495.

35. Sawaguchi N, Majima T, Iwasaki N, Funakoshi T, Shimode K, Onodera T, et al. 2006; Extracellular matrix modulates expression of cell-surface proteoglycan genes in fibroblasts. Connect Tissue Res. 47:141–8. doi: 10.1080/03008200600685459. DOI: 10.1080/03008200600685459. PMID: 16753807.

36. Kumai T, Samoto N, Hasegawa A, Noguchi H, Shiranita A, Shiraishi M, et al. 2018; Short-term efficacy and safety of hyaluronic acid injection for plantar fasciopathy. Knee Surg Sports Traumatol Arthrosc. 26:903–11. doi: 10.1007/s00167-017-4467-0. DOI: 10.1007/s00167-017-4467-0. PMID: 28255655.

37. Petrella MJ, Cogliano A, Petrella RJ. 2009; Original research: long-term efficacy and safety of periarticular hyaluronic acid in acute ankle sprain. Phys Sportsmed. 37:64–70. doi: 10.3810/psm.2009.04.1684. DOI: 10.3810/PSM.2009.04.1684. PMID: 20048489.

38. Repetto I, Biti B, Cerruti P, Trentini R, Felli L. 2017; Conservative treatment of ankle osteoarthritis: can platelet-rich plasma effectively postpone surgery? J Foot Ankle Surg. 56:362–5. doi: 10.1053/j.jfas.2016.11.015. DOI: 10.1053/j.jfas.2016.11.015. PMID: 28231968.

39. Lee K, Hwang IY, Ryu CH, Lee JW, Kang SW. 2018; Ultrasound-guided hyaluronic acid injection for the management of Morton's neuroma. Foot Ankle Int. 39:201–4. doi: 10.1177/1071100717739578. DOI: 10.1177/1071100717739578. PMID: 29153007.

40. Carulli C, Civinini R, Martini C, Linari S, Morfini M, Tani M, et al. 2012; Viscosupplementation in haemophilic arthropathy: a long-term follow-up study. Haemophilia. 18:e210–4. doi: 10.1111/j.1365-2516.2011.02654.x. DOI: 10.1111/j.1365-2516.2011.02654.x. PMID: 21951693.

41. Taylor S, David J, Partington K, Pemberton S, Mangles S, Wells A, et al. 2022; A single centre, open label, pilot study evaluating the effect of intra-articular hyaluronic acid injection on pain and functionality when injected into the ankle (tibio-talar and sub-talar) joint in patients with haemophilic arthropathy. Haemophilia. 28:e181–8. doi: 10.1111/hae.14639. DOI: 10.1111/hae.14639. PMID: 35905300.

42. Yoon JY, Jo CH. 2018; Platelet-rich plasma injection. J Korean Orthop Assoc. 53:381–92. doi: 10.4055/jkoa.2018.53.5.381. DOI: 10.4055/jkoa.2018.53.5.381. PMID: 31775816. PMCID: PMC6880602.

43. Sun SF, Hsu CW, Lin GC, Lin HS, Chou YJ, Wu SY, et al. 2021; Efficacy and safety of a single intra-articular injection of platelet-rich plasma on pain and physical function in patients with ankle osteoarthritis-a prospective study. J Foot Ankle Surg. 60:676–82. doi: 10.1053/j.jfas.2020.12.003. DOI: 10.1053/j.jfas.2020.12.003. PMID: 33549423.

44. Blanco-Rivera J, Elizondo-Rodríguez J, Simental-Mendía M, Vilchez-Cavazos F, Peña-Martínez VM, Acosta-Olivo C. 2020; Treatment of lateral ankle sprain with platelet-rich plasma: a randomized clinical study. Foot Ankle Surg. 26:750–4. doi: 10.1016/j.fas.2019.09.004. DOI: 10.1016/j.fas.2019.09.004. PMID: 31640921.

45. Henning PR, Grear BJ. 2018; Platelet-rich plasma in the foot and ankle. Curr Rev Musculoskelet Med. 11:616–23. doi: 10.1007/s12178-018-9522-z. DOI: 10.1007/s12178-018-9522-z. PMID: 30259330. PMCID: PMC6220005.

46. Ferrari M, Zia S, Valbonesi M, Henriquet F, Venere G, Spagnolo S, et al. 1987; A new technique for hemodilution, preparation of autologous platelet-rich plasma and intraoperative blood salvage in cardiac surgery. Int J Artif Organs. 10:47–50. doi: 10.1177/039139888701000111. DOI: 10.1177/039139888701000111. PMID: 3570542.

47. Anitua E. 1999; Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants. 14:529–35. PMID: 10453668.

48. Kawasumi M, Kitoh H, Siwicka KA, Ishiguro N. 2008; The effect of the platelet concentration in platelet-rich plasma gel on the regeneration of bone. J Bone Joint Surg Br. 90:966–72. doi: 10.1302/0301-620X.90B7.20235. DOI: 10.1302/0301-620X.90B7.20235. PMID: 18591611.

49. Creaney L, Hamilton B. 2008; Growth factor delivery methods in the management of sports injuries: the state of play. Br J Sports Med. 42:314–20. doi: 10.1136/bjsm.2007.040071. DOI: 10.1136/bjsm.2007.040071. PMID: 17984193.

50. Pavlovic V, Ciric M, Jovanovic V, Stojanovic P. 2016; Platelet rich plasma: a short overview of certain bioactive components. Open Med (Wars). 11:242–7. doi: 10.1515/med-2016-0048. DOI: 10.1515/med-2016-0048. PMID: 28352802. PMCID: PMC5329835.

51. Tsai WC, Yu TY, Lin LP, Lin MS, Tsai TT, Pang JS. 2017; Platelet rich plasma promotes skeletal muscle cell migration in association with up-regulation of FAK, paxillin, and F-Actin formation. J Orthop Res. 35:2506–12. doi: 10.1002/jor.23547. DOI: 10.1002/jor.23547. PMID: 28233384.

52. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. 2004; Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 91:4–15. doi: 10.1160/TH03-07-0440. DOI: 10.1160/TH03-07-0440. PMID: 14691563.

53. Marx RE. 2001; Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 10:225–8. doi: 10.1097/00008505-200110000-00002. DOI: 10.1097/00008505-200110000-00002. PMID: 11813662.

54. Guzel Y, Karalezli N, Bilge O, Kacira BK, Esen H, Karadag H, et al. 2015; The biomechanical and histological effects of platelet-rich plasma on fracture healing. Knee Surg Sports Traumatol Arthrosc. 23:1378–83. doi: 10.1007/s00167-013-2734-2. DOI: 10.1007/s00167-013-2734-2. PMID: 24170188.

55. Paget LDA, Reurink G, de Vos RJ, Weir A, Moen MH, Bierma-Zeinstra SMA, et al. PRIMA Study Group. 2021; Effect of platelet-rich plasma injections vs placebo on ankle symptoms and function in patients with ankle osteoarthritis: a randomized clinical trial. JAMA. 326:1595–605. doi: 10.1001/jama.2021.16602. DOI: 10.1001/jama.2021.16602. PMID: 34698782. PMCID: PMC8548954.

56. Kearney RS, Ji C, Warwick J, Parsons N, Brown J, Harrison P, et al. ATM Trial Collaborators. 2021; Effect of platelet-rich plasma injection vs sham injection on tendon dysfunction in patients with chronic midportion Achilles tendinopathy: a randomized clinical trial. JAMA. 326:137–44. doi: 10.1001/jama.2021.6986. DOI: 10.1001/jama.2021.6986. PMID: 34255009. PMCID: PMC8278266.

57. Hohmann E, Tetsworth K, Glatt V. 2021; Platelet-rich plasma versus corticosteroids for the treatment of plantar fasciitis: a systematic review and meta-analysis. Am J Sports Med. 49:1381–93. doi: 10.1177/0363546520937293. DOI: 10.1177/0363546520937293. PMID: 32822236.

58. Dolkart O, Chechik O, Zarfati Y, Brosh T, Alhajajra F, Maman E. 2014; 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. 134:1271–7. doi: 10.1007/s00402-014-2026-4. DOI: 10.1007/s00402-014-2026-4. PMID: 25027676.

59. de Jonge S, de Vos RJ, Weir A, van Schie HT, Bierma-Zeinstra SM, Verhaar JA, et al. 2011; One-year follow-up of platelet-rich plasma treatment in chronic Achilles tendinopathy: a double-blind randomized placebo-controlled trial. Am J Sports Med. 39:1623–9. doi: 10.1177/0363546511404877. DOI: 10.1177/0363546511404877. PMID: 21602565.

60. de Vos RJ, Weir A, van Schie HT, Bierma-Zeinstra SM, Verhaar JA, Weinans H, et al. 2010; Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA. 303:144–9. doi: 10.1001/jama.2009.1986. DOI: 10.1001/jama.2009.1986. PMID: 20068208.

61. Krogh TP, Ellingsen T, Christensen R, Jensen P, Fredberg U. 2016; Ultrasound-guided injection therapy of Achilles tendinopathy with platelet-rich plasma or saline: a randomized, blinded, placebo-controlled trial. Am J Sports Med. 44:1990–7. doi: 10.1177/0363546516647958. DOI: 10.1177/0363546516647958. PMID: 27257167.

62. Madhi MI, Yausep OE, Khamdan K, Trigkilidas D. 2020; The use of PRP in treatment of Achilles Tendinopathy: a systematic review of literature. Study design: systematic review of literature. Ann Med Surg (Lond). 55:320–6. doi: 10.1016/j.amsu.2020.04.042. DOI: 10.1016/j.amsu.2020.04.042. PMID: 32566217. PMCID: PMC7298400.

63. Schepull T, Kvist J, Norrman H, Trinks M, Berlin G, Aspenberg P. 2011; Autologous platelets have no effect on the healing of human achilles tendon ruptures: a randomized single-blind study. Am J Sports Med. 39:38–47. doi: 10.1177/0363546510383515. DOI: 10.1177/0363546510383515. PMID: 21051425.

64. Kaniki N, Willits K, Mohtadi NG, Fung V, Bryant D. 2014; A retrospective comparative study with historical control to determine the effectiveness of platelet-rich plasma as part of nonoperative treatment of acute achilles tendon rupture. Arthroscopy. 30:1139–45. doi: 10.1016/j.arthro.2014.04.086. DOI: 10.1016/j.arthro.2014.04.086. PMID: 24997748.

65. Boesen AP, Boesen MI, Hansen R, Barfod KW, Lenskjold A, Malliaras P, et al. 2020; Effect of platelet-rich plasma on nonsurgically treated acute Achilles tendon ruptures: a randomized, double-blinded prospective study. Am J Sports Med. 48:2268–76. doi: 10.1177/0363546520922541. DOI: 10.1177/0363546520922541. PMID: 32485112.

66. Jain SK, Suprashant K, Kumar S, Yadav A, Kearns SR. 2018; Comparison of plantar fasciitis injected with platelet-rich plasma vs corticosteroids. Foot Ankle Int. 39:780–6. doi: 10.1177/1071100718762406. DOI: 10.1177/1071100718762406. PMID: 29600719.

67. Laver L, Carmont MR, McConkey MO, Palmanovich E, Yaacobi E, Mann G, et al. 2015; Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial. Knee Surg Sports Traumatol Arthrosc. 23:3383–92. doi: 10.1007/s00167-014-3119-x. DOI: 10.1007/s00167-014-3119-x. PMID: 24938396.

68. Fukawa T, Yamaguchi S, Akatsu Y, Yamamoto Y, Akagi R, Sasho T. 2017; Safety and efficacy of intra-articular injection of platelet-rich plasma in patients with ankle osteoarthritis. Foot Ankle Int. 38:596–604. doi: 10.1177/1071100717700377. DOI: 10.1177/1071100717700377. PMID: 28399635.

69. Guney A, Akar M, Karaman I, Oner M, Guney B. 2015; Clinical outcomes of platelet rich plasma (PRP) as an adjunct to microfracture surgery in osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc. 23:2384–9. doi: 10.1007/s00167-013-2784-5. DOI: 10.1007/s00167-013-2784-5. PMID: 24292979.

70. Görmeli G, Karakaplan M, Görmeli CA, Sarıkaya B, Elmalı N, Ersoy Y. 2015; Clinical effects of platelet-rich plasma and hyaluronic acid as an additional therapy for talar osteochondral lesions treated with microfracture surgery: a prospective randomized clinical trial. Foot Ankle Int. 36:891–900. doi: 10.1177/1071100715578435. DOI: 10.1177/1071100715578435. PMID: 25825393.

71. Reurink G, Goudswaard GJ, Moen MH, Weir A, Verhaar JA, Bierma-Zeinstra SM, et al. Dutch Hamstring Injection Therapy (HIT) Study Investigators. 2014; Platelet-rich plasma injections in acute muscle injury. N Engl J Med. 370:2546–7. doi: 10.1056/NEJMc1402340. DOI: 10.1056/NEJMc1402340. PMID: 24963588.

72. Roffi A, Di Matteo B, Krishnakumar GS, Kon E, Filardo G. 2017; Platelet-rich plasma for the treatment of bone defects: from pre-clinical rational to evidence in the clinical practice. A systematic review. Int Orthop. 41:221–37. doi: 10.1007/s00264-016-3342-9. DOI: 10.1007/s00264-016-3342-9. PMID: 27888295.