Treatment of Tendon and Muscle Using Platelet-Rich Plasma

      Tendon and muscle injuries are common in elite and weekend athletes. Treatment of these injuries in both groups is rapidly evolving. Sports medicine patients are demanding better and less invasive solutions for all types of musculoskeletal disorders. In this context, platelet-rich plasma (PRP) has emerged as a potential solution. PRP is a fraction of whole blood containing concentrated growth factors and proteins. These cytokines direct tissue healing through autocrine and paracrine effects. The number of basic science, animal, and human investigations of PRP for tendon and muscle injuries worldwide has risen sharply in recent years. These studies are helping clinicians better understand the mechanisms of PRP and are guiding novel treatment protocols. In this paper, the value of PRP as a treatment for acute or chronic tendon and muscle disorders is explored.

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      References

      1. The burden of musculoskeletal diseases in the United States. Source: medical expenditures panel survey, Agency for Healthcare and Quality, U.S. Department of Health and Human services, 1996–2004.

        • Knighton D.R.
        • Hunt T.K.
        • Thakral K.K.
        • et al.
        Role of platelets and fibrin in the healing sequence: an in vivo study of angiogenesis and collagen synthesis.
        Ann Surg. 1982; 196: 379-388
        • Dallari D.
        • Savarino L.
        • Stagni C.
        • et al.
        Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells.
        J Bone Joint Surg Am. 2007; 89: 2413-2420
        • Carreon L.
        • Glassman S.
        • Anekstein Y.
        • et al.
        Platelet gel (AGF) fails to increase fusion rates in instrumented posterolateral fusions.
        Spine. 2005; 30 ([discussion: E247]): E243-E246
        • Ranly D.M.
        • Lohmann C.H.
        • Andreacchio D.
        • et al.
        Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in nude mice.
        J Bone Joint Surg Am. 2007; 89: 139-147
        • Weiner B.K.
        • Walker M.
        Autologous growth factors and lumbar intertransverse fusions.
        Spine. 2003; 28 ([discussion: 1971]): 1968-1970
        • Jenis L.G.
        • Banco R.J.
        • Kwon B.
        A prospective study of autologous growth factors (AGF) in lumbar interbody fusion.
        Spine J. 2006; 6 ([E pub 2005 Dec 6]): 14-20
        • Kitoh H.
        • Kitakoji T.
        • Tsuchiya H.
        • et al.
        Distraction osteogenesis of the lower extremity with achondroplasia/hypochondroplasia treated with transplantation of culture-expanded bone marrow cells and platelet-rich plasma.
        J Pediatr Orthop. 2007; 27: 629-634
        • Mishra A.
        • Pavelko T.
        Treatment of chronic elbow tendinosis with buffered platelet-rich plasma.
        Am J Sports Med. 2006; 34: 1774-1778
        • Sanchez M.
        • Anitua E.
        • Azofra J.
        • et al.
        Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices.
        Am J Sports Med. 2007; 35: 245-251
        • Marx R.
        Platelet rich plasma (PRP): what is PRP and what is not PRP?.
        Implant Dent. 2001; 10: 225-228
        • Horsburgh Jr., C.R.
        • Clark R.A.
        • Kirkpatrick C.H.
        Lymphokines and platelets promote human monocyte adherence to fibrinogen and fibronectin in vitro.
        J Leukoc Biol. 1987; 41: 14-24
        • Bielecki T.M.
        • Gazdzik T.S.
        • Arendt J.
        • et al.
        Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study.
        J Bone Joint Surg Br. 2007; 89: 417-420
        • Moojem D.J.
        • Everts P.A.
        • Schure R.M.
        • et al.
        Antimicrobial activity of platelet-leukocyte gel against Staphyloccus aureus.
        J Orthop Res. 2008; 26: 404-410
        • Fufa D.
        • Shealy B.
        • Jacobson M.
        • et al.
        Activation of platelet-rich plasma using soluble Type I collagen.
        J Oral Maxillofac Surg. 2008; 66: 684-690
        • Rodeo S.
        Biologic augmentation of rotator cuff tendon repair.
        J Shoulder Elbow Surg. 2007; 16: S191-S197
        • Liu Y.
        • Kalén A.
        • Risto O.
        • et al.
        Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent.
        Wound Repair Regen. 2002; 10: 336-340
        • Borzini P.
        • Mazzucco I.
        Platelet-rich plasma (PRP) and platelet derivatives for topical therapy. What is true from the biologic view point?.
        ISBT Science Series. 2007; 2: 272-281
        • Eppley B.L.
        • Woodell J.E.
        • Higgins J.
        Platelet quantification and growth factor analysis from platelet rich plasma: implications for wound healing.
        Plast Reconstr Surg. 2004; 114: 1502-1508
        • Everts P.A.
        • Jakimowicz J.J.
        • van Beek M.
        • et al.
        Reviewing the structural features of autologous platelet-leukocyte gel and suggestions for use in surgery.
        Eur Surg Res. 2007; 39: 199-207
        • Eppley B.L.
        • Pietrzak W.S.
        • Blanton M.
        Platelet-rich plasma: a review of biology and applications in plastic surgery.
        Plast Reconstr Surg. 2006; 118 ([review]): 147e-159e
        • Hope M.
        • Saxby T.S.
        Tendon healing.
        Foot Ankle Clin. 2007; 12: 553-567
        • Awad A.S.
        • Huang L.
        • Ye H.
        • et al.
        Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy.
        Am J Physiol Renal Physiol. 2006; 290 ([Epub 2005 Dec 6]): F828-F837
        • Cronstein B.M.
        Adenosine receptors and wound healing, revised.
        ScientificWorldJournal. 2006; 6: 984-991
        • Németh Z.H.
        • Lutz C.S.
        • Csóka B.
        • et al.
        Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism.
        J Immunol. 2005; 175: 8260-8270
        • Cruz C.M.
        • Rinna A.
        • Forman H.J.
        • et al.
        ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages.
        J Biol Chem. 2007; 282 ([Epub 2006 Nov 27]): 2871-2879
        • Parratt J.R.
        • West G.B.
        Release of 5-hydroxytryptamine and histamine from tissues of the rat.
        J Physiol. 1957; 137: 179-192
        • Los G.
        • De Weger R.A.
        • Van den Berg D.T.
        • et al.
        Macrophage infiltration in tumors and tumor-surrounding tissue: influence of serotonin and sensitized lymphocytes.
        Cancer Immunol Immunother. 1988; 26: 145-152
        • Sternberg E.M.
        • Trial J.
        • Parker C.W.
        Effect of serotonin on murine macrophages: suppression of Ia expression by serotonin and its reversal by 5-HT2 serotonergic receptor antagonists.
        J Immunol. 1986; 137: 276-282
        • Majno G.
        • Gilmore V.
        • Leventhal M.
        On the mechanism of vascular leakage caused by histaminetype mediators. A microscopic study in vivo.
        Circ Res. 1967; 21: 833-847
        • Lansdown A.B.
        Calcium: a potential central regulator in wound healing in the skin.
        Wound Repair Regen. 2002; 10 ([review]): 271-285
        • Nho S.J.
        • Yadav H.
        • Shindle M.K.
        • et al.
        Rotator cuff degeneration: etiology and pathogenesis.
        Am J Sports Med. 2008; 36 ([Epub 2008 Apr 15]): 987-993
        • Khaliq Y.
        • Zhanel G.G.
        Fluoroquinolone-associated tendinopathy: a critical review of the literature.
        Clin Infect Dis. 2003; 36 ([review]) ([Epub 2003 May 20]): 1404-1410
        • Xu Y.
        • Murrell G.A.
        The basic science of tendinopathy.
        Clin Orthop Relat Res. 2008; 466: 1528-1538
        • Wang J.H.
        • Iosifidis M.I.
        • Fu F.H.
        Biomechanical basis for tendinopathy.
        Clin Orthop Relat Res. 2006; 443: 320-332
        • Sharma P.
        • Maffulli N.
        Tendon injury and tendinopathy: healing and repair.
        J Bone Joint Surg Am. 2005; 87 ([review]): 187-202
        • Würgler-Hauri C.C.
        • Dourte L.M.
        • Baradet T.C.
        • et al.
        Temporal expression of 8 growth factors in tendon-to-bone healing in a rat supraspinatus model.
        J Shoulder Elbow Surg. 2007; 16: S198-S203
        • Lucarelli E.
        • Beccheroni A.
        • Donati D.
        • et al.
        Platelet-derived growth factors enhance proliferation of human stromal stem cells.
        Biomaterials. 2003; 24: 3095-3100
        • Woodall J.R.
        • Tucci M.
        • Mishra A.
        • et al.
        Cellular effects of platelet rich plasma: a study on HL-60 macrophage-like cells.
        Biomed Sci Instrum. 2007; 43: 266-271
        • Woodall Jr., J.
        • Mishra A.
        • Tucci M.
        • et al.
        Cellular Effects of Platelet Rich Plasma: Interleukin-1 release from PRP treated macrophage cells.
        Biomed Sci Instrum. 2008; 44: 489-494
        • Kawamura S.
        • Ying L.
        • Kim H.J.
        • et al.
        Macrophages accumulate in the early phase of tendon-bone healing.
        J Orthop Res. 2005; 23 ([Epub 2005 Aug 19]): 1425-1432
        • Bi Y.
        • Ehirchiou D.
        • Kilts T.M.
        • et al.
        Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.
        Nat Med. 2007; 13 ([Epub 2007 Sep 9]): 1219-1227
        • Schnabel L.V.
        • Mohammed H.O.
        • Miller B.J.
        • et al.
        Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons.
        J Orthop Res. 2007; 25: 230-240
        • de Mos M.
        • van der Windt A.
        • Jahr H.
        • et al.
        Can platelet-rich plasma enhance tendon repair? A cell culture study.
        Am J Sports Med. 2008; 36: 1171-1178
        • Anitua E.
        • Sanchez M.
        • Nurden A.T.
        • et al.
        Reciprocal actions of platelet-secreted TGF-beta1 on the production of VEGF and HGF by human tendon cells.
        Plast Reconstr Surg. 2007; 119: 950-959
        • Aspenberg P.
        • Virchenko O.
        Platelet concentrate injection improves Achilles tendon repair in rats.
        Acta Orthop Scand. 2004; 75: 93-99
        • Virchenko O.
        • Aspenberg P.
        How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation.
        Acta Orthop Scand. 2006; 77: 806-812
        • Kajikawa Y.
        • Morihara T.
        • Sakamoto H.
        • et al.
        Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing.
        J Cell Physiol. 2008; 215: 837-845
        • Randelli P.
        • Arrigoni P.
        • Cabitza P.
        • et al.
        Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study.
        Disabil Rehabil. 2008; 00: 1-6
        • Gamradt S.C.
        • Rodeo S.A.
        • Warren R.F.
        Platelet rich plasma in rotator cuff repair.
        Tech Orthop Surg. 2007; 22: 26-33
      2. Gosen T, Sluimer J. Prospective randomized study on the effect of autologous platelets injection in lateral epicondylitis compared with corticosteroid injection. Poster presented at: 13th Congress of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA); May 21–24, 2008; Porto, Portugal. Poster P25–444.

        • Jarvinen T.A.
        • Jarvinen T.L.
        • Kaariainen M.
        • et al.
        Muscle injuries: biology and treatment.
        Am J Sports Med. 2005; 33: 745-764
        • Ryan A.J.
        Quadriceps strain, rupture, and Charlie horse.
        Med Sci Sports. 1969; 1: 106-111
        • Yokota K.
        • Ishida O.
        • Sunagawa T.
        • et al.
        Platelet-rich plasma accelerated surgical angiogenesis in vascular-implanted necrotic bone: an experimental study in rabbits.
        Acta Orthop. 2008; 79: 106-110
        • Sariguney Y.
        • Yavuzer R.
        • Elmas C.
        • et al.
        Effect of platelet-rich plasma on peripheral nerve regeneration.
        J Reconstr Microsurg. 2008; 24: 159-167
        • Shen W.
        • Prisk V.
        • Li Y.
        • et al.
        Inhibited skeletal muscle healing in cyclooxygenase-2 gene-deficient mice: the role of PGE2 and PGF2alpha.
        J Appl Phys. 2006; 101: 1215-1221
        • Kasemkijwattana C.
        • Menetrey J.
        • Bosch P.
        • et al.
        Use of growth factors to improve muscle healing after strain injury.
        Clin Orthop Relat Res. 2000; 370: 272-285
        • Shen W.
        • Li Y.
        • Zhu J.
        • et al.
        Interaction between macrophages, TGF-beta1, and the COX-2 pathway during inflammatory phase of skeletal muscle healing after injury.
        J Cell Physiol. 2008; 214: 405-412
        • Menetrey J.
        • Kasemkijwattana C.
        • Day C.
        • et al.
        Growth factors improve muscle healing in vivo.
        J Bone Joint Surg Br. 2000; 82-B: 131-137
        • Wright-Carpenter T.
        • Opolon P.
        • Appell J.
        • et al.
        Treatment of muscle injuries by local administration of autologous conditioned serum: animal experiments using a muscle contusion model.
        Int J Sports Med. 2004; 25: 582-587
        • Sanchez M.
        • Anitua E.
        • Andia I.
        Application of autologous growth factors on skeletal muscle healing.
        Regmed. 2005; (Poster Presentation. Available at:) (Accessed May 15, 2008)
        • Vogel J.P.
        • Szalay K.
        • Geiger F.
        • et al.
        Platelet-rich plasma improves expansion of human mesenchymal stem cells and retains differentiation capacity and in vivo bone formation in calcium phosphate.
        Platelets. 2006; 17: 462-469
        • Aspenberg P.
        Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review.
        Int Orthop. 2007; 31 ([Epub 2007 Jun]): 783-789