Abstract
Platelet concentrates such as platelet-rich plasma (PRP) have gained considerable popularity in regenerative medicine. In orthopedic surgery they are of special interest in the management of tissues that heal only slowly or not at all. Tendons and ligaments, for example the rotator cuff of the shoulder and the anterior cruciate ligament (ACL) of the knee, are prime candidates. Our research has focused on the effect of PRP on ACL healing as an alternative to ACL reconstruction with a graft after injury. In this chapter we will explain in detail what we have come to know about PRP production, about PRP constituents, and about the use of PRP in tendon and ligament repair with a special focus on the ACL. Briefly, we recommend the use of a 3X or lower platelet concentration within the PRP and suggest allowing for leukocyte and maybe even erythrocyte “contamination”, owing to the microbicidal effect and plentiful growth-factor release of leukocytes and the stimulation of collagen production by erythrocytes. Most importantly, we suggest that each clinical application should have a PRP preparation tailored for it. Finally, in the light of the added benefit of cell types other than platelets we encourage researchers and commercial providers of PRP machines to describe the cell mix of the employed platelet concentrates as exactly as possible.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abe S, Kurosaka M, Iguchi T (1993) Light and electron microscopic study of remodeling and maturation process in autogenous graft for anterior cruciate ligament reconstruction. Arthroscopy 9:394–405
Adachi N, Ochi M, Uchio Y, Iwasa J, Ryoke K, Kuriwaka M (2002) Mechanoreceptors in the anterior cruciate ligament contribute to the joint position sense. Acta Orthop Scand 73(3):330–334
Andrade MG, de Freitas Brandão CJ, Sá CN, de Bittencourt TC, Sadigursky M (2008) Evaluation of factors that can modify platelet-rich plasma properties. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(1):e5–e12
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(4):529–535
Aspenberg P (2007) Stimulation of tendon repair: mechanical loading, GDFs and platelets: a mini review. Int Orthop 31(6):783–789
Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008) Growth factors and cytokine in wound healing. Wound Repair Regen 16(5):585–601
Boyce DE, Jones WD, Ruge F, Harding KG, Moore K (2000) The role of lymphocytes in human dermal wound healing. Br J Dermatol 143(1):59–65
Castillo TN, Pouliot MA, Kim HJ, Dragoo JL (2010) Comparison of growth factor and platelet concentrations from commercial platelet-rich plasma separation systems. Am J Sports Med 39:266–271
Castricini R, Longo UG, De Benedetto M, Panfoli N, Pirani P, Zini R et al (2010) Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med 39(2):258–265
Chircop MP, Yu Y, Berney CR, Yang JL, Crowe PJ, Walsh WR (2002) Wound healing and growth factor expression in T lymphocyte deficiency. ANZ J Surg 72(7):491–495
Cho S, Muneta T, Ito S (2004) Electron microscopic evaluation of two-bundle anatomically reconstructed anterior cruciate ligament graft. J Orthop Sci 9:296–301
Cieslik-Bielecka A, Gazdik TS, Bielecki TM, Cieslik T (2007) Why the platelet-rich gel has antimicrobial activity? Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:303–305
de Vos RJ, Weir A, Tol JL, Verhaar JA, Weinans H, van Schie HT (2010a) No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midportion Achilles tendinopathy. Br J Sports Med 45(5):387–392
de Vos RJ, Weir A, van Schie HT, Bierma-Zeinstra SM, Verhaar JA, Weinans H et al (2010b) Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA 303(2):144–149
Efron JE, Frankel HL, Lazarou SA, Wasserkrug HL, Barbul A (1990) Wound healing and T-lymphocytes. J Surg Res 1990 48(5):460–463
Dohan Ehrenfest DM (2010) Shedding light in the controversial terminology for platelet-rich products: Platelet-rich plasma (PRP), platelet-rich fibrin (PRF), platelet-leukocyte gel (PLG), preparation rich in growth factors (PRGF), classification and commercialism. J Biomed Mater Res A 95(4):1280–1282
Dohan Ehrenfest DM, Rasmusson L, Albrektsson T (2009) Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol 27(3):158–167
Ekdahl M, Wang JH, Ronga M, Fu FH (2008) Graft healing in anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 16(10):935–947
Everts PA, van Zundert A, Schönberger JP, Devilee RJ, Knape JT (2008) What do we use: platelet-rich plasma or platelet-leukocyte gel? J Biomed Mater Res A 85(4):1135–1136
Falconiero R, DiStefano V, Cook T (1998) Revascularization and ligamentization of autogenous anterior cruciate ligament grafts in humans. Arthroscopy 14:197–205
Fredriksson K, Stridh H, Lundahl J, Rennard SI, Skold CM (2004) Red blood cells inhibit proliferation and stimulate apoptosis in human lung fibroblasts in vitro. Scand J Immunol 59(6):559–565
Ferrara N (1999) Vascular endothelial growth factor: molecular and biological aspects. Curr Top Microbiol Immunol 237:1–30
Gomez-Barrena E, Bonsfills N, Martin JG, Ballesteros-Masso R, Foruria A, Nunez-Molina A (2008) Insufficient recovery of neuromuscular activity around the knee after experimental anterior cruciate ligament reconstruction. Acta Orthop 79(1):39–47
Gow AJ, Stamler JS (1998) Reactions between nitric oxide and haemoglobin under physiological conditions. Nature 391:169–173
Griffin L, Albohm M, Arendt E (2006) Understanding and preventing noncontact anterior cruciate ligament injuries. Am J Sports Med 34:1512–1532
Hantash BM, Zhao L, Knowles JA, Lorenz HP (2008) Adult and fetal wound healing. Front Biosci 13:51–61
Harrison SL, Vavken P, Murray MM (2011) Erythrocytes inhibit ligament fibroblast proliferation in a collagen scaffold. J Orthop Res. doi:10.1002/jor.21321
Howell S, Knox K, Farley T, Taylor M (1995) Revascularization of a human anterior cruciate ligament graft during the first two years of implantation. Am J Sports Med 23:42–49
Jacobson M, Fufa D, Abreu EL, Kevy S, Murray MM (2008) Platelets, but not erythrocytes, significantly affect cytokine release and scaffold contraction in a provisional scaffold model. Wound Repair Regen 16:370–378
Jia L, Bonaventura C, Bonaventura J, Stamler JS (1996) S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 380:221–226
Johnson L (1993) The outcome of a free autogenous semitendinosus tendon graft in human anterior cruciate reconstructive surgery: a histological study. Arthroscopy 9:131–142
Joshi S, Mastrangelo A, Murray M (2009) Collagen-platelet composite enhances histologic healing of the ACL. 55th ORS, Las Vegas, 22–25 Feb. 2009
Kasama T, Miwa Y, Isozaki T, Odai T, Adachi M, Kunkel SL (2005) Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy 4(3):273–279
Keen D (2008) A review of research examining the regulatory role of lymphocytes in normal wound healing. J Wound Care 17(5):218–220
Lanzetta A, Corradini C, Verdoia C, Miani A, Castano S, Castano P (2004) The nervous structures of anterior cruciate ligament of human knee, healthy and lesioned, studied with confocal scanning laser microscopy. Ital J Anat Embryol 109(3):167–176
Li WY, Chong SS, Huang EY, Tuan TL (2003) Plasminogen activator/plasmin system: a major player in wound healing? Wound repair Regen 11(4):239–247
Lyras DN, Kazakos K, Tryfonidis M, Agrogiannis G, Botaitis S, Kokka A et al (2010) Temporal and spatial expression of TGF-beta1 in an Achilles tendon section model after application of platelet-rich plasma. Foot Ankle Surg 16(3):137–141
Lyras DN, Kazakos K, Verettas D, Polychronidis A, Tryfonidis M, Botaitis S et al (2009) The influence of platelet-rich plasma on angiogenesis during the early phase of tendon healing. Foot Ankle Int 30(11):1101–1106
Malech HL (2007) The role of neutrophils in the immune system: an overview. Methods Mol Biol 412:3–11
Maniscalco P, Gambera D, Lunati A, Vox G, Fossombroni V, Beretta R et al (2008) The “Cascade” membrane: a new PRP device for tendon ruptures. Description and case report on rotator cuff tendon. Acta Biomed 79(3):223–226
Martin CW, Muir IF (1990) The role of lymphocytes in wound healing. Br J Plast Surg 43:655–662
Mastrangelo AN, Vavken P, Fleming BC, Harrison SL, Murray MM (2011) Reduced platelet concentration does not harm PRP effectiveness for ACL repair in a porcine in vivo model. J Orthop Res 29(7):1002–1007
Moojen DJ, Everts PA, Schure RM, Overdevest EP, van Zundert A, Knape JT, Castelein RM, Creemers LB, Dhert WJ (2008) Antimicrobial activity of platelet-leukocyte gel against Staphylococcus aureus. J Orthop Res 26:404–410
Murray MM, Spindler KP, Abreu E, Muller JA, Nedder A, Kelly M et al (2007) Collagen-platelet rich plasma hydrogel enhances primary repair of the porcine anterior cruciate ligament. J Orthop Res 25(1):81–91
Nishio N, Ito S, Suzuki H, Isobe K (2009) Antibodies to wounded tissue enhance cutaneous wound healing. Immunology 128(3):369–380
Ochi M, Iwasa J, Uchio Y, Adachi N, Sumen Y (1999) The regeneration of sensory neurones in the reconstruction of the anterior cruciate ligament. J Bone Joint Surg Br 81(5):902–906
Orrego M, Larrain C, Rosales J, Valenzuela L, Matas J, Durruty J et al (2008) Effects of platelet concentrate and a bone plug on the healing of hamstring tendons in a bone tunnel. Arthroscopy 24(12):1373–1380
Park JE, Barbul A (2004) Understanding the role of immune regulation in wound healing. Am J Surg 187(5):S115–S116
Peterson JM, Barbul A, Breslin RJ, Wasserkrug HL, Efron G (1987) Significance of T-lymphocytes in wound healing. Surgery 102(2):300–305
Radice F, Yanez R, Gutierrez V, Rosales J, Pinedo M, Coda S (2010) Comparison of magnetic resonance imaging findings in anterior cruciate ligament grafts with and without autologous platelet-derived growth factors. Arthroscopy 26(1):50–57
Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N (2008) Autologous platelet rich plasma for arthroscopic rotator cuff repair: a pilot study. Disabil Rehabil 30(20–22):1584–1589
Riddle JM, Barnhart MI (1965) The eosinophil as a source of profibrinolysin in acute inflammation. Blood 25:776–794
Rodeo SA (2007) Biologic augmentation of rotator cuff tendon repair. J Shoulder Elbow Surg 16(5 Suppl):S191–S197
Savill JS, Wylie AH, Henson JE et al (1989) Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J Clin Invest 83(3):865–875
Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6(12):1191–1197
Shaffer MR, Efron PA, Thornton FJ (1997) Nitric oxide, an autocrine regulator of wound fibroblast synthetic function. J Immunol 158:2375–2381
Silvers HJ, Mandelbaum BR (2007) Prevention of anterior cruciate ligament injury in the female athlete. Br J Sports Med 41(1 Suppl):i52–i59
Singer AJ, Clark RA (1999) Cutaneous wound healing. NEJM 341(10):738–746
Song BZ, Donoff RB, Tsuji T, Todd R, Gallagher GT, Wong DT (1993) Identification of rabbit eosinophils and heterophils in cutaneous healing wounds. Histochem J 25(10):762–771
Tanimoto Y, Takahashi K, Kimura I (1992) Effects of cytokines on human basophil chemotaxis. Clin Exp Allergy 22(11):1020–1025
Tohidnezhad M, Varoga D, Wruck CJ, Brandenburg LO, Seekamp A, Shakibaei M et al (2011) Platelet-released growth factors can accelerate tenocyte proliferation and activate the anti-oxidant response element. Histochem Cell Biol 135(5):453–460
Valeriani M, Restuccia D, Di Lazzaro V, Franceschi F, Fabbriciani C, Tonali P (1999) Clinical and neurophysiological abnormalities before and after reconstruction of the anterior cruciate ligament of the knee. Acta Neurol Scand 99(5):303–307
Ventura A, Terzaghi C, Bordo E, Verdoia C, Gallazi M, Failoni S (2005) Use of growth factors in ACL surgery: preliminary study. J Orthopaed Traumatol 6:76–79
Virchenko O, Aspenberg P (2006) 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 77(5):806–812
Vogrin M, Rupreht M, Dinevski D, Haspl M, Kuhta M, Jevsek M et al (2010) Effects of a platelet gel on early graft revascularization after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind, clinical trial. Eur Surg Res 45(2):77–85
Weibrich G et al (2005) Comparison of the platelet concentrate collection system with the platelet-rich-in growth-factors kit to produce platelet-rich plasma: a technical report
Weiler A, Peine R, Pashmineh-Azar A, Abel C, Sudkamp NP, Hoffmann RF (2002a) Tendon healing in a bone tunnel. Part I. Biomechanical results after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep. Arthroscopy 18(2):113–123
Weiler A, Hoffmann RF, Bail HJ, Rehm O, Sudkamp NP (2002b) Tendon healing in a bone tunnel. Part II. Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep. Arthroscopy 18(2):124–135
Witte MB, Thornton FJ, Efron DT (2000) Enhancement of fibroblast collagen synthesis by nitric oxide. Nitric Oxide 4:572–582
Zeinoun T, Aftimos G, Bou Saba S, Nammour S (2009) Eosinophils and mastocytes in healing laser excision wounds. Lasers Med Sci 24(3):307–312
Zimmerman R et al (2001) Different preparation methods to obtain platelet components as a source of growth factors for local application. Transfusion 41(10):1217–1224
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Chao, L., Murray, M.M., Vavken, P. (2014). Platelet-Rich Plasma (PRP) in Ligament and Tendon Repair. In: Lana, J., Andrade Santana, M., Dias Belangero, W., Malheiros Luzo, A. (eds) Platelet-Rich Plasma. Lecture Notes in Bioengineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40117-6_10
Download citation
DOI: https://doi.org/10.1007/978-3-642-40117-6_10
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-40116-9
Online ISBN: 978-3-642-40117-6
eBook Packages: EngineeringEngineering (R0)