Platelet-rich plasma therapy - future or trend?

Robinder S Dhillon, Edward M Schwarz, Michael D Maloney, Robinder S Dhillon, Edward M Schwarz, Michael D Maloney

Abstract

Chronic complex musculoskeletal injuries that are slow to heal pose challenges to physicians and researchers alike. Orthobiologics is a relatively newer science that involves application of naturally found materials from biological sources (for example, cell-based therapies), and offers exciting new possibilities to promote and accelerate bone and soft tissue healing. Platelet-rich plasma (PRP) is an orthobiologic that has recently gained popularity as an adjuvant treatment for musculoskeletal injuries. It is a volume of fractionated plasma from the patient's own blood that contains platelet concentrate. The platelets contain alpha granules that are rich in several growth factors, such as platelet-derived growth factor, transforming growth factor-β, insulin-like growth factor, vascular endothelial growth factor and epidermal growth factor, which play key roles in tissue repair mechanisms. PRP has found application in diverse surgical fields to enhance bone and soft-tissue healing by placing supra-physiological concentrations of autologous platelets at the site of tissue damage. The relative ease of preparation, applicability in the clinical setting, favorable safety profile and possible beneficial outcome make PRP a promising therapeutic approach for future regenerative treatments. However, there is a large knowledge gap in our understanding of PRPs mechanism of action, which has raised skepticism regarding its potential efficacy and use. Thus, the aim of this review is to describe the various factors proposed to contribute to the biological activity of PRP, and the published pre-clinical and clinical evidence to support it. Additionally, we describe the current techniques and technology for PRP preparation, and review the present shortcomings of this therapy that will need to be overcome if it is to gain broad acceptance.

Figures

Figure 1
Figure 1
The three-step process of platelet-rich plasma (PRP) treatment.
Figure 2
Figure 2
Bases for potential classification systems for platelet-rich plasma (PRP).

References

    1. Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10:225–228. doi: 10.1097/00008505-200110000-00002.
    1. Schwarz A. A Promising Treatment for Athletes, in Blood. The New York Times; 2009.
    1. Platelet Rich Plasma: a Market Snapshot.
    1. March L, Woolf AD. The global burden of musculoskeletal conditions - why is it important? Best Pract Res Clin Rheumatol. 2010;24:721. doi: 10.1016/j.berh.2011.01.001.
    1. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003;81:646–656.
    1. Banfi G, Corsi MM, Volpi P. Could platelet rich plasma have effects on systemic circulating growth factors and cytokine release in orthopaedic applications? Br J Sports Med. 2006;40:816. doi: 10.1136/bjsm.2006.029934.
    1. Praemer AF. Musculoskeletal Conditions in the United States. 2. Rosemont: American Academy of Orthopaedic Surgeons; 1999.
    1. Marx RE, Garg AK. Dental and Craniofacial Applications of Platelet-Rich Plasma. Carol Stream: Quintessence Publishing Co., Inc.; 2005.
    1. Academy of Sciences, Paris: M. Donné on the Blood Globules. Prov Med Surg J (1840) 1842;3:498–499.
    1. Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med. 2008;1:165–174. doi: 10.1007/s12178-008-9032-5.
    1. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003;83:835–870.
    1. Anitua E, Sánchez M, Nurden AT, Nurden P, Orive G, Andía I. New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol. 2006;24:227–234. doi: 10.1016/j.tibtech.2006.02.010.
    1. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62:489–496. doi: 10.1016/j.joms.2003.12.003.
    1. Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte-and platelet-rich fibrin (L-PRF) Trends Biotechnol. 2009;27:158–167. doi: 10.1016/j.tibtech.2008.11.009.
    1. Yu W, Wang J, Yin J. Platelet-rich plasma: a promising product for treatment of peripheral nerve regeneration after nerve injury. Int J Neurosci. 2011;121:176–180. doi: 10.3109/00207454.2010.544432.
    1. Weibrich G, Kleis WK, Hafner G, Hitzler WE, Wagner W. Comparison of platelet, leukocyte, and growth factor levels in point-of-care platelet-enriched plasma, prepared using a modified Curasan kit, with preparations received from a local blood bank. Clin Oral Implants Res. 2003;14:357–162. doi: 10.1034/j.1600-0501.2003.00810.x.
    1. Gonshor A. Technique for producing platelet-rich plasma and platelet concentrate: background and process. Int J Periodontics Restorative Dent. 2002;22:547–557.
    1. Borrione P, Gianfrancesco AD, Pereira MT, Pigozzi F. Platelet-rich plasma in muscle healing. Am J Phys Med Rehabil. 2010;89:854–861. doi: 10.1097/PHM.0b013e3181f1c1c7.
    1. Christgau M, Moder D, Hiller KA, Dada A, Schmitz G, Schmalz G. Growth factors and cytokines in autologous platelet concentrate and their correlation to periodontal regeneration outcomes. J Clin Periodontol. 2006;33:837–845. doi: 10.1111/j.1600-051X.2006.00991.x.
    1. Sanchez AR, Sheridan PJ, Kupp LI. Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants. 2003;18:93–103.
    1. Lyras DN, Kazakos K, Agrogiannis G, Verettas D, Kokka A, Kiziridis G, Chronopoulos E, Tryfonidis M. Experimental study of tendon healing early phase: is IGF-1 expression influenced by platelet rich plasma gel? Orthop Traumatol Surg Res. 2010;96:381–387. doi: 10.1016/j.otsr.2010.03.010.
    1. Zapf J, Waldvogel M, Froesch ER. Binding of nonsuppressible insulinlike activity to human serum. Evidence for a carrier protein. Arch Biochem Biophys. 1975;168:638–645. doi: 10.1016/0003-9861(75)90296-9.
    1. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978;253:2769–2776.
    1. Froesch ER, Schmid C, Schwander J, Zapf J. Actions of insulin-like growth factors. Annu Rev Physiol. 1985;47:443–467. doi: 10.1146/annurev.ph.47.030185.002303.
    1. Hwang DL, Latus LJ, Lev-Ran A. Effects of platelet-contained growth factors (PDGF, EGF, IGF-I, and TGF-beta) on DNA synthesis in porcine aortic smooth muscle cells in culture. Exp Cell Res. 1992;200:358–360. doi: 10.1016/0014-4827(92)90183-9.
    1. Spencer EM, Tokunaga A, Hunt TK. Insulin-like growth factor binding protein-3 is present in the alpha-granules of platelets. Endocrinology. 1993;132:996–1001. doi: 10.1210/en.132.3.996.
    1. Weibrich G, Kleis WK, Hafner G. Growth factor levels in the platelet-rich plasma produced by 2 different methods: curasan-type PRP kit versus PCCS PRP system. Int J Oral Maxillofac Implants. 2002;17:184–190.
    1. Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res. 2005;84:434–439. doi: 10.1177/154405910508400507.
    1. Schmidmaier G, Herrmann S, Green J, Weber T, Scharfenberger A, Haas NP, Wildemann B. Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation. Bone. 2006;39:1156–1163. doi: 10.1016/j.bone.2006.05.023.
    1. Ferrari M, Zia S, Valbonesi M, Henriquet F, Venere G, Spagnolo S, Grasso MA, Panzani I. A new technique for hemodilution, preparation of autologous platelet-rich plasma and intraoperative blood salvage in cardiac surgery. Int J Artif Organs. 1987;10:47–50.
    1. Storrs C. Is Platelet-Rich Plasma an Effective Healing Therapy? Scientific American. 2009.
    1. Cieslik-Bielecka A, Bielecki T, Gazdzik TS, Arendt J, Król W, Szczepanski T. Autologous platelets and leukocytes can improve healing of infected high-energy soft tissue injury. Transfus Apher Sci. 2009;41:9–12. doi: 10.1016/j.transci.2009.05.006.
    1. Sánchez M, Azofra J, Anitua E, Andía I, Padilla S, Santisteban J, Mujika I. Plasma rich in growth factors to treat an articular cartilage avulsion: a case report. Med Sci Sports Exerc. 2003;35:1648–1652. doi: 10.1249/01.MSS.0000089344.44434.50.
    1. Tomoyasu A, Higashio K, Kanomata K, Goto M, Kodaira K, Serizawa H, Suda T, Nakamura A, Nojima J, Fukuda T, Katagiri T. Platelet-rich plasma stimulates osteoblastic differentiation in the presence of BMPs. Biochem Biophys Res Commun. 2007;361:62–67. doi: 10.1016/j.bbrc.2007.06.142.
    1. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;427(Suppl):S27–36.
    1. Anitua E, Sánchez M, Nurden AT, Zalduendo MM, de la Fuente M, Azofra J, Andía I. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology (Oxford) 2007;46:1769–1772. doi: 10.1093/rheumatology/kem234.
    1. Liu Y, Kalén A, Risto O, Wahlström O. Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen. 2002;10:336–340. doi: 10.1046/j.1524-475X.2002.10510.x.
    1. Packer DL, Dombi GW, Yu PY, Zidel P, Sullivan WG. An in vitro model of fibroblast activity and adhesion formation during flexor tendon healing. J Hand Surg Am. 1994;19:769–776. doi: 10.1016/0363-5023(94)90181-3.
    1. Bernard-Beaubois K, Hecquet C, Houcine O, Hayem G, Adolphe M. Culture and characterization of juvenile rabbit tenocytes. Cell Biol Toxicol. 1997;13:103–113.
    1. Schulze-Tanzil G, Mobasheri A, Clegg PD, Sendzik J, John T, Shakibaei M. Cultivation of human tenocytes in high-density culture. Histochem Cell Biol. 2004;122:219–228. doi: 10.1007/s00418-004-0694-9.
    1. Anitua E, Andía I, Sanchez M, Azofra J, del Mar Zalduendo M, de la Fuente M, Nurden P, Nurden A. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res. 2005;23:281–286. doi: 10.1016/j.orthres.2004.08.015.
    1. de Mos M, van der Windt AE, Jahr H, van Schie HT, Weinans H, Verhaar JA, van Osch GJ. Can platelet-rich plasma enhance tendon repair? A cell culture study. Am J Sports Med. 2008;36:1171–1178. doi: 10.1177/0363546508314430.
    1. Ni M, Tang P, Wang Y, Li G. [Experimental study on promoting bone consolidation by using platelet-rich plasma and decalcified bone matrix during distraction osteogenesis] Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011;25:661–667.
    1. 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;37:1135–1142. doi: 10.1177/0363546508330974.
    1. Sun Y, Feng Y, Zhang CQ, Chen SB, Cheng XG. The regenerative effect of platelet-rich plasma on healing in large osteochondral defects. Int Orthop. 2010;34:589–597. doi: 10.1007/s00264-009-0793-2.
    1. Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA. Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons. J Orthop Res. 2007;25:230–240. doi: 10.1002/jor.20278.
    1. Lyras DN, Kazakos K, Verettas D, Polychronidis A, Tryfonidis M, Botaitis S, Agrogiannis G, Simopoulos C, Kokka A, Patsouris E. The influence of platelet-rich plasma on angiogenesis during the early phase of tendon healing. Foot Ankle Int. 2009;30:1101–1106. doi: 10.3113/FAI.2009.1101.
    1. Lyras DN, Kazakos K, Verettas D, Botaitis S, Agrogiannis G, Kokka A, Pitiakoudis M, Kotzakaris A. The effect of platelet-rich plasma gel in the early phase of patellar tendon healing. Arch Orthop Trauma Surg. 2009;129:1577–1582. doi: 10.1007/s00402-009-0935-4.
    1. Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E, Ayeni OR, Bhandari M. Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am. 2012;94:298–307. doi: 10.2106/JBJS.K.00154.
    1. 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;35:245–251.
    1. Schepull T, Kvist J, Norrman H, Trinks M, Berlin G, Aspenberg P. Autologous platelets have no effect on the healing of human achilles tendon ruptures: a randomized single-blind study. Am J Sports Med. 2011;39:38–47. doi: 10.1177/0363546510383515.
    1. Filardo G, Presti ML, Kon E, Marcacci M. Nonoperative biological treatment approach for partial Achilles tendon lesion. Orthopedics. 2010;33:120–123. doi: 10.3928/01477447-20100104-31.
    1. Vogrin M, Rupreht M, Dinevski D, Hašpl M, Kuhta M, Jevsek M, Knežević M, Rožman P. Effects of a platelet gel on early graft revascularization after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind, clinical trial. Eur Surg Res. 2010;45:77–85. doi: 10.1159/000318597.
    1. Vogrin M, Rupreht M, Crnjac A, Dinevski D, Krajnc Z, Recnik G. The effect of platelet-derived growth factors on knee stability after anterior cruciate ligament reconstruction: a prospective randomized clinical study. Wien Klin Wochenschr. 2010;122(Suppl 2):91–95.
    1. Gardner MJ, Demetrakopoulos D, Klepchick PR, Mooar PA. The efficacy of autologous platelet gel in pain control and blood loss in total knee arthroplasty. An analysis of the haemoglobin, narcotic requirement and range of motion. Int Orthop. 2007;31:309–313. doi: 10.1007/s00264-006-0174-z.
    1. Everts PA, Devilee RJ, Brown Mahoney C, Eeftinck-Schattenkerk M, Box HA, Knape JT, van Zundert A. Platelet gel and fibrin sealant reduce allogeneic blood transfusions in total knee arthroplasty. Acta Anaesthesiol Scand. 2006;50:593–599. doi: 10.1111/j.1399-6576.2006.001005.x.
    1. 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. Am J Sports Med. 2011;39:1200–1208. doi: 10.1177/0363546510397173.
    1. Hechtman KS, Uribe JW, Botto-vanDemden A, Kiebzak GM. Platelet-rich plasma injection reduces pain in patients with recalcitrant epicondylitis. Orthopedics. 2011;34:92.
    1. Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cuscó X, Garcia-Balletbó M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011;131:311–317. doi: 10.1007/s00402-010-1167-3.
    1. Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2010;19:528–535.
    1. Randelli P, Arrigoni P, Ragone V, Aliprandi A, Cabitza P. Platelet rich plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year follow-up. J Shoulder Elbow Surg. 2011;20:518–528. doi: 10.1016/j.jse.2011.02.008.
    1. Castricini R, Longo UG, De Benedetto M, Panfoli N, Pirani P, Zini R, Maffulli N, Denaro V. Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med. 2011;39:258–265. doi: 10.1177/0363546510390780.
    1. Everts PA, Devilee RJ, Brown Mahoney C, van Erp A, Oosterbos CJ, Stellenboom M, Knape JT, van Zundert A. Exogenous application of platelet-leukocyte gel during open subacromial decompression contributes to improved patient outcome. A prospective randomized double-blind study. Eur Surg Res. 2008;40:203–210. doi: 10.1159/000110862.
    1. Everts PA, Knape JT, Weibrich G, Schönberger JP, Hoffmann J, Overdevest EP, Box HA, van Zundert A. Platelet-rich plasma and platelet gel: a review. J Extra Corpor Technol. 2006;38:174–187.
    1. Anitua E, Orive G. Short implants in maxillae and mandibles: a retrospective study with 1 to 8 years of follow-up. J Periodontol. 2010;81:819–826. doi: 10.1902/jop.2010.090637.
    1. Anitua E, Orive G, Aguirre JJ, Ardanza B, Andía I. 5-year clinical experience with BTI dental implants: risk factors for implant failure. J Clin Periodontol. 2008;35:724–732. doi: 10.1111/j.1600-051X.2008.01248.x.
    1. Spero JA. Bovine thrombin-induced inhibitor of factor V and bleeding risk in postoperative neurosurgical patients. Report of three cases. J Neurosurg. 1993;78:817–820. doi: 10.3171/jns.1993.78.5.0817.
    1. Cmolik BL, Spero JA, Magovern GJ, Clark R. Redo cardiac surgery: late bleeding complications from topical thrombin-induced factor V deficiency. J Thorac Cardiovasc Surg. 1993;105:222–227. discussion 227-228.
    1. Ortel TL, Mercer MC, Thames EH, Moore KD, Lawson JH. Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin. Ann Surg. 2001;233:88–96. doi: 10.1097/00000658-200101000-00014.
    1. World Anti-Doping Agency. The World Anti-Doping Code. The 2010 Prohibited List. International Standard.
    1. World Anti-Doping Agency. The World Anti-Doping Code. The 2010 Prohibited List. International Standard.
    1. Wright-Carpenter T, Klein P, Schäferhoff P, Appell HJ, Mir LM, Wehling P. Treatment of muscle injuries by local administration of autologous conditioned serum: a pilot study on sportsmen with muscle strains. Int J Sports Med. 2004;25:588–593. doi: 10.1055/s-2004-821304.
    1. Borselli C, Storrie H, Benesch-Lee F, Shvartsman D, Cezar C, Lichtman JW, Vandenburgh HH, Mooney DJ. Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc Natl Acad Sci USA. 2010;107:3287–3292. doi: 10.1073/pnas.0903875106.
    1. Daugherty K, Porucznik MA. Treating tendons, bones, and cartilage with PRP.
    1. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med. 2006;34:1774–1778. doi: 10.1177/0363546506288850.
    1. Porucznik MA. PRP an unproven option, agree forum experts.
    1. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plastic Reconstruct Surg. 2004;114:1502–1508.
    1. Engebretsen L, Steffen K, Alsousou J, Anitua E, Bachl N, Devilee R, Everts P, Hamilton B, Huard J, Jenoure P, Kelberine F, Kon E, Maffulli N, Matheson G, Mei-Dan O, Menetrey J, Philippon M, Randelli P, Schamasch P, Schwellnus M, Vernec A, Verrall G. IOC consensus paper on the use of platelet-rich plasma in sports medicine. Br J Sports Med. 2010;44:1072–1081. doi: 10.1136/bjsm.2010.079822.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj