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Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction

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Abstract

Platelet-rich plasma (PRP) has been tested in vitro, in animal models, and clinically for its efficacy in enhancing the rate of wound healing, reducing pain associated with injuries, and promoting axon regeneration. Although extensive data indicate that PRP-released factors induce these effects, the claims are often weakened because many studies were not rigorous or controlled, the data were limited, and other studies yielded contrary results. Critical to assessing whether PRP is effective are the large number of variables in these studies, including the method of PRP preparation, which influences the composition of PRP; type of application; type of wounds; target tissues; and diverse animal models and clinical studies. All these variables raise the question of whether one can anticipate consistent influences and raise the possibility that most of the results are correct under the circumstances where PRP was tested. This review examines evidence on the potential influences of PRP and whether PRP-released factors could induce the reported influences and concludes that the preponderance of evidence suggests that PRP has the capacity to induce all the claimed influences, although this position cannot be definitively argued. Well-defined and rigorously controlled studies of the potential influences of PRP are required in which PRP is isolated and applied using consistent techniques, protocols, and models. Finally, it is concluded that, because of the purported benefits of PRP administration and the lack of adverse events, further animal and clinical studies should be performed to explore the potential influences of PRP.

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References

  1. Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E et al (2012) Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am 94:298

    Article  PubMed  Google Scholar 

  2. 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 25:81

    Article  PubMed  Google Scholar 

  3. Oliveira MR, deC Silva A, Ferreira S, Avelino CC, Garcia IR, Jr., Mariano RC (2015) Influence of the association between platelet-rich fibrin and bovine bone on bone regeneration. A histomorphometric study in the calvaria of rats. Int J Oral Maxillofac Surg 44(5):649–655

  4. Sanchez M, Anitua E, Delgado D, Sanchez P, Orive G, Padilla S (2014) Muscle repair: platelet-rich plasma derivates as a bridge from spontaneity to intervention. Injury 45(4):S7

    Article  PubMed  Google Scholar 

  5. Nacopoulos C, Dontas I, Lelovas P, Galanos A, Vesalas AM, Raptou P et al (2014) Enhancement of bone regeneration with the combination of platelet-rich fibrin and synthetic graft. J Craniofac Surg 25:2164

    PubMed  Google Scholar 

  6. Viswanatham V, Snehalatha C, Mathai T, Jayaraman M, Ramachandran A (1998) Cardio vascular morbidity in proteinuric south Indian NIDDM patients. Diabetes Res Clin Pract 39:63

    Article  CAS  PubMed  Google Scholar 

  7. Karunakar P, Prasanna JS, Jayadev M, Shravani GS (2014) Platelet-rich fibrin, “a faster healing aid” in the treatment of combined lesions: a report of two cases. J Indian Soc Periodontol 18:651

    Article  PubMed Central  PubMed  Google Scholar 

  8. Su CY, Kuo YP, Nieh HL, Tseng YH, Burnouf T (2008) Quantitative assessment of the kinetics of growth factors release from platelet gel. Transfusion 48:2414

    Article  CAS  PubMed  Google Scholar 

  9. Peterson JE, Zurakowski D, Italiano JE Jr, Michel LV, Fox L, Klement GL et al (2010) Normal ranges of angiogenesis regulatory proteins in human platelets. Am J Hematol 85:487

    Article  CAS  PubMed  Google Scholar 

  10. Kakudo N, Morimoto N, Kushida S, Ogawa T, Kusumoto K (2014) Platelet-rich plasma releasate promotes angiogenesis in vitro and in vivo. Med Mol Morphol 47(2):83–89

    Article  CAS  PubMed  Google Scholar 

  11. Kuffler DP (2013) Platelet-rich plasma and the elimination of neuropathic pain. Mol Neurobiol 48:315

    Article  CAS  PubMed  Google Scholar 

  12. Kuo YP, Lee YL, Tseng YH, Su CH, Burnouf T, Su CY (2010) Influence of ethanol on the release of growth factors in human blood-derived platelet gels. Biologicals 38:120

    Article  CAS  PubMed  Google Scholar 

  13. Burnouf T, Goubran HA, Chen TM, Ou KL, El-Ekiaby M, Radosevic M (2013) Blood-derived biomaterials and platelet growth factors in regenerative medicine. Blood Rev 27:77

    Article  CAS  PubMed  Google Scholar 

  14. Martinello T, Bronzini I, Perazzi A, Testoni S, De Benedictis GM, Negro A et al (2013) Effects of in vivo applications of peripheral blood-derived mesenchymal stromal cells (PB-MSCs) and platelet-rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep. J Orthop Res 31:306

    Article  CAS  PubMed  Google Scholar 

  15. Lichtenfels M, Colome L, Sebben AD, Braga-Silva J (2013) Effect of platelet rich plasma and platelet rich fibrin on sciatic nerve regeneration in a rat model. Microsurgery 33:383

    Article  PubMed  Google Scholar 

  16. 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 30:1101

    Article  PubMed  Google Scholar 

  17. 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 45:77

    Article  CAS  PubMed  Google Scholar 

  18. Lyras DN, Kazakos K, Georgiadis G, Mazis G, Middleton R, Richards S et al (2011) Does a single application of PRP alter the expression of IGF-I in the early phase of tendon healing? J Foot Ankle Surg 50:276

    Article  PubMed  Google Scholar 

  19. Sarrafian TL, Wang H, Hackett ES, Yao JQ, Shih MS, Ramsay HL et al (2010) Comparison of Achilles tendon repair techniques in a sheep model using a cross-linked acellular porcine dermal patch and platelet-rich plasma fibrin matrix for augmentation. J Foot Ankle Surg 49:128

    Article  PubMed  Google Scholar 

  20. Milano G, Sanna Passino E, Deriu L, Careddu G, Manunta L, Manunta A et al (2010) The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: an experimental study in a sheep model. Osteoarthritis Cartilage/OARS 18:971

    Article  CAS  Google Scholar 

  21. Bosch G, Rene van Weeren P, Barneveld A, van Schie HT (2011) Computerised analysis of standardised ultrasonographic images to monitor the repair of surgically created core lesions in equine superficial digital flexor tendons following treatment with intratendinous platelet rich plasma or placebo. Vet J 187:92

    Article  PubMed  Google Scholar 

  22. Tsuzuki N, Otsuka K, Seo J, Yamada K, Haneda S, Furuoka H et al (2012) In vivo osteoinductivity of gelatin beta-tri-calcium phosphate sponge and bone morphogenetic protein-2 on an equine third metacarpal bone defect. Res Vet Sci 93:1021

    Article  CAS  PubMed  Google Scholar 

  23. Matsunaga D, Akizuki S, Takizawa T, Omae S, Kato H (2013) Compact platelet-rich fibrin scaffold to improve healing of patellar tendon defects and for medial collateral ligament reconstruction. Knee 20:545

    Article  PubMed  Google Scholar 

  24. Mishra A, Velotta J, Brinton TJ, Wang X, Chang S, Palmer O et al (2011) RevaTen platelet-rich plasma improves cardiac function after myocardial injury. Cardiovasc Revasc Med 12:158

    Article  PubMed  Google Scholar 

  25. Gigante A, Del Torto M, Manzotti S, Cianforlini M, Busilacchi A, Davidson PA et al (2012) Platelet rich fibrin matrix effects on skeletal muscle lesions: an experimental study. J Biol Regul Homeost Agents 26:475

    CAS  PubMed  Google Scholar 

  26. Hammond JW, Hinton RY, Curl LA, Muriel JM, Lovering RM (2009) Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med 37:1135

    Article  PubMed Central  PubMed  Google Scholar 

  27. Kazakos K, Lyras DN, Verettas D, Tilkeridis K, Tryfonidis M (2009) The use of autologous PRP gel as an aid in the management of acute trauma wounds. Injury 40:801

    Article  CAS  PubMed  Google Scholar 

  28. Farrag TY, Lehar M, Verhaegen P, Carson KA, Byrne PJ (2007) Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model. Laryngoscope 117:157

    Article  PubMed  Google Scholar 

  29. Giannessi E, Coli A, Stornelli MR, Miragliotta V, Pirone A, Lenzi C et al (2014) An autologously generated platelet-rich plasma suturable membrane may enhance peripheral nerve regeneration after neurorrhaphy in an acute injury model of sciatic nerve neurotmesis. J Reconstr Microsurg 30:617

    Article  PubMed  Google Scholar 

  30. Ye F, Li H, Qiao G, Chen F, Tao H, Ji A et al (2012) Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury. Neural Regen Res 7:2286

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Nin JR, Gasque GM, Azcarate AV, Beola JD, Gonzalez MH (2009) Has platelet-rich plasma any role in anterior cruciate ligament allograft healing? Arthroscopy 25:1206

    Article  PubMed  Google Scholar 

  32. Castricini R, Longo UG, De Benedetto M, Panfoli N, Pirani P, Zini R et al (2011) Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med 39:258

    Article  PubMed  Google Scholar 

  33. Silva A, Sampaio R (2009) Anatomic ACL reconstruction: does the platelet-rich plasma accelerate tendon healing? Knee Surg Sports Traumatol Arthrosc 17:676

    Article  PubMed  Google Scholar 

  34. Saur SJ, Sangkhae V, Geddis AE, Kaushansky K, Hitchcock IS (2010) Ubiquitination and degradation of the thrombopoietin receptor c-Mpl. Blood 115:1254

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. 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 26:50

    Article  PubMed  Google Scholar 

  36. Barber FA, Hrnack SA, Snyder SJ, Hapa O (2011) Rotator cuff repair healing influenced by platelet-rich plasma construct augmentation. Arthroscopy 27:1029

    Article  PubMed  Google Scholar 

  37. Randelli P, Arrigoni P, Ragone V, Aliprandi A, Cabitza P (2011) Platelet rich plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year follow-up. J Shoulder Elbow Surg/Am Shoulder Elbow Surg 20(4):518–528

    Article  Google Scholar 

  38. Filardo G, Kon E, Della Villa S, Vincentelli F, Fornasari PM, Marcacci M (2010) Use of platelet-rich plasma for the treatment of refractory jumper’s knee. Int Orthop 34:909

    Article  PubMed Central  PubMed  Google Scholar 

  39. Donoghoe N, Rosson GD, Dellon AL (2007) Reconstruction of the human median nerve in the forearm with the Neurotube. Microsurgery 27:595

    Article  PubMed  Google Scholar 

  40. Creaney L (2011) Platelet-rich plasma and the biological complexity of tissue regeneration. Br J Sports Med 45:611

    Article  PubMed  Google Scholar 

  41. Mifune Y, Matsumoto T, Takayama K, Ota S, Li H, Meszaros LB et al (2013) The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthritis Cartilage 21:175

    Article  CAS  PubMed  Google Scholar 

  42. Sanchez M, Anitua E, Azofra J, Prado R, Muruzabal F, Andia I (2010) Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology. Arthroscopy 26:470

    Article  PubMed  Google Scholar 

  43. Uysal AC, Mizuno H (2011) Differentiation of adipose-derived stem cells for tendon repair. Methods Mol Biol 702:443

    Article  CAS  PubMed  Google Scholar 

  44. Lusini M, Di Martino A, Spadaccio C, Rainer A, Chello M, Fabbrocini M et al (2012) Resynthesis of sternal dehiscence with autologous bone graft and autologous platelet gel. J Wound Care 21:74

    Article  CAS  PubMed  Google Scholar 

  45. Vavken P, Saad FA, Fleming BC, Murray MM (2011) VEGF receptor mRNA expression by ACL fibroblasts is associated with functional healing of the ACL. Knee Surg Sports Traumatol Arthrosc 19:1675

    Article  PubMed Central  PubMed  Google Scholar 

  46. Uysal CA, Tobita M, Hyakusoku H, Mizuno H (2012) Adipose-derived stem cells enhance primary tendon repair: biomechanical and immunohistochemical evaluation. J Plast Reconstr Aesthet Surg 65:1712

    Article  PubMed  Google Scholar 

  47. Jo CH, Kim JE, Yoon KS, Shin S (2012) Platelet-rich plasma stimulates cell proliferation and enhances matrix gene expression and synthesis in tenocytes from human rotator cuff tendons with degenerative tears. Am J Sports Med 40:1035

    Article  PubMed  Google Scholar 

  48. Lee JW, Kwon OH, Kim TK, Cho YK, Choi KY, Chung HY et al (2013) Platelet-rich plasma: quantitative assessment of growth factor levels and comparative analysis of activated and inactivated groups. Arch Plast Surg 40:530

    Article  PubMed Central  PubMed  Google Scholar 

  49. Li H, Usas A, Poddar M, Chen CW, Thompson S, Ahani B et al (2013) Platelet-rich plasma promotes the proliferation of human muscle derived progenitor cells and maintains their stemness. PLoS One 8:e64923

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Zhang J, Wang JH (2010) Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. Am J Sports Med 38:2477

    Article  PubMed  Google Scholar 

  51. Visser LC, Arnoczky SP, Caballero O, Egerbacher M (2010) Platelet-rich fibrin constructs elute higher concentrations of transforming growth factor-beta1 and increase tendon cell proliferation over time when compared to blood clots: a comparative in vitro analysis. Vet Surg: VS 39:811

    Article  PubMed  Google Scholar 

  52. Lyras DN, Kazakos K, Agrogiannis G, Verettas D, Kokka A, Kiziridis G et al (2010) Experimental study of tendon healing early phase: is IGF-1 expression influenced by platelet rich plasma gel? Orthop Traumatol Surg Res 96:381

    Article  CAS  PubMed  Google Scholar 

  53. 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 16:137

    Article  PubMed  Google Scholar 

  54. von der Mark K, Osdoby P, Caplan AI (1982) Effect of 4-methylumbelliferyl-beta-d-xyloside on collagen synthesis in chick limb bud mesenchymal cell cultures. Dev Biol 90:24

    Article  PubMed  Google Scholar 

  55. Lohmander LS, Hascall VC, Caplan AI (1979) Effects of 4-methyl umbelliferyl-beta-D-xylopyranoside on chondrogenesis and proteoglycan synthesis in chick limb bud mesenchymal cell cultures. J Biol Chem 254:10551

    CAS  PubMed  Google Scholar 

  56. Carvalho MD, Suaid FF, Santamaria MP, Casati MZ, Nociti FH Jr, Sallum AW et al (2011) Platelet-rich plasma plus bioactive glass in the treatment of intra-bony defects: a study in dogs. J Appl Oral Sci : revista FOB 19:82

    Article  PubMed Central  PubMed  Google Scholar 

  57. Ozdemir B, Kurtis B, Tuter G, Senguven B, Tokman B, Pinar-Ozdemir S et al (2012) Double-application of platelet-rich plasma on bone healing in rabbits. Med Oral Patol Oral Cir Bucal 17:e171

    Article  PubMed Central  PubMed  Google Scholar 

  58. Miloro M, Haralson DJ, Desa V (2010) Bone healing in a rabbit mandibular defect using platelet-rich plasma. J Oral Maxillofac Surg 68:1225

    Article  PubMed  Google Scholar 

  59. Broggini N, Hofstetter W, Hunziker E, Bosshardt DD, Bornstein MM, Seto I et al (2011) The influence of PRP on early bone formation in membrane protected defects. A histological and histomorphometric study in the rabbit calvaria. Clin Implant Dent Relat Res 13:1

    Article  PubMed  Google Scholar 

  60. Giovanini AF, Deliberador TM, Gonzaga CC, de Oliveira Filho MA, Gohringer I, Kuczera J et al (2010) Platelet-rich plasma diminishes calvarial bone repair associated with alterations in collagen matrix composition and elevated CD34+ cell prevalence. Bone 46:1597

    Article  CAS  PubMed  Google Scholar 

  61. Li H, Hamza T, Tidwell JE, Clovis N, Li B (2013) Unique antimicrobial effects of platelet-rich plasma and its efficacy as a prophylaxis to prevent implant-associated spinal infection. Adv Healthcare Mater 2(9):1277–1284

    Article  CAS  Google Scholar 

  62. Suaid FF, Carvalho MD, Ambrosano GM, Nociti FH Jr, Casati MZ, Sallum EA (2012) Platelet-rich plasma in the treatment of class II furcation defects: a histometrical study in dogs. J Appl Oral Sci : revista FOB 20:162

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Montanari M, Callea M, Yavuz I, Maglione M (2013) A new biological approach to guided bone and tissue regeneration. BMJ Case Rep. doi:10.1136/bcr-2012-008240

  64. Hakimi M, Jungbluth P, Sager M, Betsch M, Herten M, Becker J et al (2010) Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs. Injury 41:717

    Article  CAS  PubMed  Google Scholar 

  65. Ezirganli S, Kazancioglu HO, Mihmanli A, Sharifov R, Aydin MS (2014) Effects of different biomaterials on augmented bone volume resorptions. Clin Oral Implants Res. doi:10.1111/clr.12495

  66. Batista MA, Leivas TP, Rodrigues CJ, Arenas GC, Belitardo DR, Guarniero R (2011) Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia. Clinics 66:1787

    Article  PubMed Central  PubMed  Google Scholar 

  67. Zhang YD, Wang G, Sun Y, Zhang CQ (2011) Combination of platelet-rich plasma with degradable bioactive borate glass for segmental bone defect repair. Acta Orthop Belg 77:110

    PubMed  Google Scholar 

  68. Gallo I, Saenz A, Artinano E, Esquide J (2010) Autologous platelet-rich plasma: effect on sternal healing in the sheep model. Interact Cardiovasc Thorac Surg 11:223

    Article  PubMed  Google Scholar 

  69. Monteiro BS, Argolo-Neto NM, Nardi NB, Chagastelles PC, Carvalho PH, Bonfa LP et al (2012) Treatment of critical defects produced in calvaria of mice with mesenchymal stem cells. An Acad Bras Cienc 84:841

    Article  CAS  PubMed  Google Scholar 

  70. Panda S, Jayakumar ND, Sankari M, Varghese SS, Kumar DS (2014) Platelet rich fibrin and xenograft in treatment of intrabony defect. Contemp Clin Dent 5:550

    Article  PubMed Central  PubMed  Google Scholar 

  71. Passaretti F, Tia M, D’Esposito V, De Pascale M, Del Corso M, Sepulveres R et al (2014) Growth-promoting action and growth factor release by different platelet derivatives. Platelets 25:252

    Article  CAS  PubMed  Google Scholar 

  72. Serra-Mestre JM, Serra-Renom JM, Martinez L, Almadori A, D’Andrea F (2014) Platelet-rich plasma mixed-fat grafting: a reasonable prosurvival strategy for fat grafts? Aesthetic Plast Surg 38:1041

    Article  PubMed  Google Scholar 

  73. Shiu HT, Goss B, Lutton C, Crawford R, Xiao Y (2014) Formation of blood clot on biomaterial implants influences bone healing. Tissue Eng Part B Rev 20:697

    Article  CAS  PubMed  Google Scholar 

  74. Toffler M (2014) Guided bone regeneration (GBR) using cortical bone pins in combination with leukocyte- and platelet-rich fibrin (L-PRF). Compend Contin Educ Dent 35:192

    PubMed  Google Scholar 

  75. Xuan F, Lee CU, Son JS, Jeong SM, Choi BH (2014) A comparative study of the regenerative effect of sinus bone grafting with platelet-rich fibrin-mixed Bio-Oss(R) and commercial fibrin-mixed Bio-Oss(R): an experimental study. J Craniomaxillofac Surg 42:e47

    Article  PubMed  Google Scholar 

  76. Yoon JS, Lee SH, Yoon HJ (2014) The influence of platelet-rich fibrin on angiogenesis in guided bone regeneration using xenogenic bone substitutes: a study of rabbit cranial defects. J Craniomaxillofac Surg 42:1071

    Article  PubMed  Google Scholar 

  77. Jiang ZQ, Liu HY, Zhang LP, Wu ZQ, Shang DZ (2011) Repair of calvarial defects in rabbits with platelet-rich plasma as the scaffold for carrying bone marrow stromal cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 113(3):327–333

    Article  Google Scholar 

  78. Davis VL, Abukabda AB, Radio NM, Witt-Enderby PA, Clafshenkel WP, Cairone JV et al (2014) Platelet-rich preparations to improve healing. Part II: platelet activation and enrichment, leukocyte inclusion, and other selection criteria. J Oral Implantol 40:511

    Article  PubMed  Google Scholar 

  79. Ji B, Sheng L, Chen G, Guo S, Xie L, Yang B et al (2015) The combination use of platelet-rich fibrin and treated dentin matrix for tooth root regeneration by cell homing. Tissue Eng Part A 21:26

    Article  CAS  PubMed  Google Scholar 

  80. Nagaveni NB, Kumari KN, Poornima P, Reddy VS (2015) Management of an endo-perio lesion in an immature tooth using autologous platelet-rich fibrin: a case report. J Indian Soc Pedod Prev Dent 33:69

    Article  CAS  PubMed  Google Scholar 

  81. Panda S, Doraiswamy J, Malaiappan S, Varghese SS, Del Fabbro M (2014) Additive effect of autologous platelet concentrates in treatment of intrabony defects: a systematic review and meta-analysis. J Investig Clin Dent. doi:10.1111/jicd.12117

  82. Badr M, Coulthard P, Alissa R, Oliver R (2010) The efficacy of platelet-rich plasma in grafted maxillae. A randomised clinical trial. Eur J Oral Implantol 3:233

    PubMed  Google Scholar 

  83. Alissa R, Esposito M, Horner K, Oliver R (2010) The influence of platelet-rich plasma on the healing of extraction sockets: an explorative randomised clinical trial. Eur J Oral Implantol 3:121

    PubMed  Google Scholar 

  84. Inchingolo F, Tatullo M, Marrelli M, Inchingolo AM, Inchingolo AD, Dipalma G et al (2012) Regenerative surgery performed with platelet-rich plasma used in sinus lift elevation before dental implant surgery: an useful aid in healing and regeneration of bone tissue. Eur Rev Med Pharmacol Sci 16:1222

    CAS  PubMed  Google Scholar 

  85. Goyal B, Tewari S, Duhan J, Sehgal PK (2011) Comparative evaluation of platelet-rich plasma and guided tissue regeneration membrane in the healing of apicomarginal defects: a clinical study. J Endod 37:773

    Article  PubMed  Google Scholar 

  86. Quesada-Garcia MP, Prados-Sanchez E, Olmedo-Gaya MV, Munoz-Soto E, Vallecillo-Capilla M, Bravo M (2012) Dental implant stability is influenced by implant diameter and localization and by the use of plasma rich in growth factors. J Oral Maxillofac Surg 70:2761

    Article  PubMed  Google Scholar 

  87. Peck MT, Marnewick J, Stephen LX, Singh A, Patel N, Majeed A (2012) The use of leukocyte- and platelet-rich fibrin (L-PRF) to facilitate implant placement in bone-deficient sites: a report of two cases. SADJ: J South African Dent Assoc = tydskrif van die Suid-Afrikaanse Tandheelkundige Vereniging 67:54

    CAS  Google Scholar 

  88. Mooren RE, Dankers AC, Merkx MA, Bronkhorst EM, Jansen JA, Stoelinga PJ (2010) The effect of platelet-rich plasma on early and late bone healing using a mixture of particulate autogenous cancellous bone and Bio-Oss: an experimental study in goats. Int J Oral Maxillofac Surg 39:371

    Article  CAS  PubMed  Google Scholar 

  89. Curi MM, Cossolin GS, Koga DH, Zardetto C, Christianini S, Feher O et al (2011) Bisphosphonate-related osteonecrosis of the jaws—an initial case series report of treatment combining partial bone resection and autologous platelet-rich plasma. J Oral Maxillofac Surg 69:2465

    Article  PubMed  Google Scholar 

  90. Mariano R, Messora M, de Morais A, Nagata M, Furlaneto F, Avelino C et al (2010) Bone healing in critical-size defects treated with platelet-rich plasma: a histologic and histometric study in the calvaria of diabetic rat. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:72

    Article  PubMed  Google Scholar 

  91. Dominijanni A, Cristofaro MG, Brescia A, Giudice M (2012) Platelet gel in oral and maxillofacial surgery: a single-centre experience. Blood Transfus 10:200

    PubMed Central  PubMed  Google Scholar 

  92. Scala M, Gipponi M, Mereu P, Strada P, Corvo R, Muraglia A et al (2010) Regeneration of mandibular osteoradionecrosis defect with platelet rich plasma gel. In Vivo 24:889

    CAS  PubMed  Google Scholar 

  93. Celio-Mariano R, de Melo WM, Carneiro-Avelino C (2012) Comparative radiographic evaluation of alveolar bone healing associated with autologous platelet-rich plasma after impacted mandibular third molar surgery. J Oral Maxillofac Surg 70:19

    Article  PubMed  Google Scholar 

  94. Rutkowski JL, Johnson DA, Radio NM, Fennell JW (2010) Platelet rich plasma to facilitate wound healing following tooth extraction. J Oral Implantol 36:11

    Article  PubMed  Google Scholar 

  95. Tatullo M, Marrelli M, Cassetta M, Pacifici A, Stefanelli LV, Scacco S et al (2012) Platelet rich fibrin (P.R.F.) in reconstructive surgery of atrophied maxillary bones: clinical and histological evaluations. Int J Med Sci 9:872

    Article  PubMed Central  PubMed  Google Scholar 

  96. Jurkovic R, Holly D, Siebert T, Strecha J (2012) Therapy for missing lower medial incisor by means of reduced diameter implants. J Oral Implantol 38:171

    Article  PubMed  Google Scholar 

  97. Zavadil DP, Satterlee CC, Costigan JM, Holt DW, Shostrom VK (2007) Autologous platelet gel and platelet-poor plasma reduce pain with total shoulder arthroplasty. J Extra Corpor Technol 39:177

    PubMed  PubMed Central  Google Scholar 

  98. Chen L, Lu X, Li S, Sun Q, Li W, Song D (2012) Sustained delivery of BMP-2 and platelet-rich plasma-released growth factors contributes to osteogenesis of human adipose-derived stem cells. Orthopedics 35:e1402

    Article  PubMed  Google Scholar 

  99. Huang S, Jia S, Liu G, Fang D, Zhang D (2012) Osteogenic differentiation of muscle satellite cells induced by platelet-rich plasma encapsulated in three-dimensional alginate scaffold. Oral Surg Oral Med Oral Pathol Oral Radiol 114:S32

    Article  PubMed  Google Scholar 

  100. Man Y, Wang P, Guo Y, Xiang L, Yang Y, Qu Y et al (2012) Angiogenic and osteogenic potential of platelet-rich plasma and adipose-derived stem cell laden alginate microspheres. Biomaterials 33:8802

    Article  CAS  PubMed  Google Scholar 

  101. Zhang AC, Sun XC, Leng WC, Zhou JW (2009) Expression and clinical significance of platelet-derived growth factor A in placenta of pre-eclampsia. Zhonghua Fu Chan Ke Za Zhi 44:809

    CAS  PubMed  Google Scholar 

  102. Shafiei-Sarvestani Z, Oryan A, Bigham AS, Meimandi-Parizi A (2012) The effect of hydroxyapatite-hPRP, and coral-hPRP on bone healing in rabbits: radiological, biomechanical, macroscopic and histopathologic evaluation. Int J Surg 10:96

    Article  PubMed  Google Scholar 

  103. Hwang YJ, Choi JY (2010) Addition of mesenchymal stem cells to the scaffold of platelet-rich plasma is beneficial for the reduction of the consolidation period in mandibular distraction osteogenesis. J Oral Maxillofac Surg 68:1112

    Article  PubMed  Google Scholar 

  104. Jiao H, Yao J, Yang Y, Chen X, Lin W, Li Y et al (2009) Chitosan/polyglycolic acid nerve grafts for axon regeneration from prolonged axotomized neurons to chronically denervated segments. Biomaterials 30:5004

    Article  CAS  PubMed  Google Scholar 

  105. Javed F, Al-Askar M, Al-Rasheed A, Al-Hezaimi K (2011) Significance of the platelet-derived growth factor in periodontal tissue regeneration. Arch Oral Biol 56:1476

    Article  CAS  PubMed  Google Scholar 

  106. Ouyang Y, Nakao A, Han D, Zhang L (2012) Transforming growth factor-beta1 promotes nasal mucosal mast cell chemotaxis in murine experimental allergic rhinitis. ORL J Otorhinolaryngol Relat Spec 74:117

    Article  CAS  PubMed  Google Scholar 

  107. Terai M, Yasukawa K, Narumoto S, Tateno S, Oana S, Kohno Y (1999) Vascular endothelial growth factor in acute Kawasaki disease. Am J Cardiol 83:337

    Article  CAS  PubMed  Google Scholar 

  108. Tanidir ST, Yuksel N, Altintas O, Yildiz DK, Sener E, Caglar Y (2010) The effect of subconjunctival platelet-rich plasma on corneal epithelial wound healing. Cornea 29:664

    PubMed  Google Scholar 

  109. Luengo Gimeno F, Gatto SC, Croxatto JO, Ferro JI, Gallo JE (2010) In vivo lamellar keratoplasty using platelet-rich plasma as a bioadhesive. Eye (Lond) 24:368

    Article  CAS  Google Scholar 

  110. Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA (2009) Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One 4:e7965

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  111. Alio JL, Arnalich-Montiel F, Rodriguez AE (2012) The role of “eye platelet rich plasma” (E-PRP) for wound healing in ophthalmology. Curr Pharm Biotechnol 13:1257

    Article  CAS  PubMed  Google Scholar 

  112. Kim KM, Shin YT, Kim HK (2012) Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis. Jpn J Ophthalmol 56:544

    Article  CAS  PubMed  Google Scholar 

  113. Geremicca W, Fonte C, Vecchio S (2010) Blood components for topical use in tissue regeneration: evaluation of corneal lesions treated with platelet lysate and considerations on repair mechanisms. Blood Transfus 8:107

    PubMed Central  PubMed  Google Scholar 

  114. Marquez De Aracena Del Cid R, Montero De Espinosa Escoriaza I (2009) Subconjunctival application of regenerative factor-rich plasma for the treatment of ocular alkali burns. Eur J Ophthalmol 19:909

    PubMed  Google Scholar 

  115. Panda A, Jain M, Vanathi M, Velpandian T, Khokhar S, Dada T (2012) Topical autologous platelet-rich plasma eyedrops for acute corneal chemical injury. Cornea 31:989

    Article  PubMed  Google Scholar 

  116. Sandri G, Bonferoni MC, Rossi S, Ferrari F, Mori M, Del Fante C et al (2012) Thermosensitive eyedrops containing platelet lysate for the treatment of corneal ulcers. Int J Pharm 426:1

    Article  CAS  PubMed  Google Scholar 

  117. Kim SA, Ryu HW, Lee KS, Cho JW (2013) Application of platelet-rich plasma accelerates the wound healing process in acute and chronic ulcers through rapid migration and upregulation of cyclin A and CDK4 in HaCaT cells. Mol Med Rep 7:476

    CAS  PubMed  Google Scholar 

  118. Anitua E, Sanchez M, Merayo-Lloves J, De la Fuente M, Muruzabal F, Orive G (2011) Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation. Invest Ophthalmol Vis Sci 52:6066

    Article  CAS  PubMed  Google Scholar 

  119. Lopez-Plandolit S, Morales MC, Freire V, Etxebarria J, Duran JA (2010) Plasma rich in growth factors as a therapeutic agent for persistent corneal epithelial defects. Cornea 29:843

    Article  PubMed  Google Scholar 

  120. Ramphul N, Geary U (2009) Caveats in the management and diagnosis of cerebellar infarct and vertebral artery dissection. Emerg Med J 26:303

    Article  CAS  PubMed  Google Scholar 

  121. Anitua E, Muruzabal F, Alcalde I, Merayo-Lloves J, Orive G (2013) Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery. Exp Eye Res 115:153

    Article  CAS  PubMed  Google Scholar 

  122. Anitua E, Sanchez M, Zalduendo MM, de la Fuente M, Prado R, Orive G et al (2009) Fibroblastic response to treatment with different preparations rich in growth factors. Cell Prolif 42:162

    Article  CAS  PubMed  Google Scholar 

  123. Sandri G, Bonferoni MC, Rossi S, Ferrari F, Mori M, Del Fante C et al (2011) Platelet lysate formulations based on mucoadhesive polymers for the treatment of corneal lesions. J Pharm Pharmacol 63:189

    Article  CAS  PubMed  Google Scholar 

  124. Zhang J, Huang C, Feng Y, Li Y, Wang W (2012) Comparison of beneficial factors for corneal wound-healing of rat mesenchymal stem cells and corneal limbal stem cells on the xenogeneic acellular corneal matrix in vitro. Mol Vis 18:161

    PubMed Central  CAS  PubMed  Google Scholar 

  125. Yamada N, Morishige N, Yanai R, Morita Y, Kimura K, Chikama T et al (2012) Open clinical study of eye drops containing the fibronectin-derived peptide PHSRN for treatment of persistent corneal epithelial defects. Cornea 31:1408

    Article  PubMed  Google Scholar 

  126. Anitua E, Troya M, Orive G (2012) Plasma rich in growth factors promote gingival tissue regeneration by stimulating fibroblast proliferation and migration and by blocking transforming growth factor-beta1-induced myodifferentiation. J Periodontol 83:1028

    Article  CAS  PubMed  Google Scholar 

  127. Por YC, Yeow VK, Louri N, Lim TK, Kee I, Song IC (2009) Platelet-rich plasma has no effect on increasing free fat graft survival in the nude mouse. J Plast Reconstr Aesthet Surg 62:1030

    Article  PubMed  Google Scholar 

  128. Argolo Neto NM, Del Carlo RJ, Monteiro BS, Nardi NB, Chagastelles PC, de Brito AF et al (2012) Role of autologous mesenchymal stem cells associated with platelet-rich plasma on healing of cutaneous wounds in diabetic mice. Clin Exp Dermatol 37:544

    Article  CAS  PubMed  Google Scholar 

  129. Sonmez TT, Vinogradov A, Zor F, Kweider N, Lippross S, Liehn EA et al (2013) The effect of platelet rich plasma on angiogenesis in ischemic flaps in VEGFR2-luc mice. Biomaterials 34:2674

    Article  PubMed  CAS  Google Scholar 

  130. Takikawa M, Sumi Y, Ishihara M, Kishimoto S, Nakamura S, Yanagibayashi S et al (2011) PRP&F/P MPs improved survival of dorsal paired pedicle skin flaps in rats. J Surg Res 170:e189

    Article  PubMed  Google Scholar 

  131. Li W, Enomoto M, Ukegawa M, Hirai T, Sotome S, Wakabayashi Y et al (2012) Subcutaneous injections of platelet-rich plasma into skin flaps modulate proangiogenic gene expression and improve survival rates. Plast Reconstr Surg 129:858

    Article  CAS  PubMed  Google Scholar 

  132. Kim HY, Park JH, Han YS, Kim H (2013) The effect of platelet-rich plasma on flap survival in random extension of an axial pattern flap in rabbits. Plast Reconstr Surg 132:85

    Article  CAS  PubMed  Google Scholar 

  133. Carter CA, Jolly DG, Worden CE Sr, Hendren DG, Kane CJ (2003) Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing. Exp Mol Pathol 74:244

    Article  CAS  PubMed  Google Scholar 

  134. DeRossi R, Coelho AC, Mello GS, Frazilio FO, Leal CR, Facco GG et al (2009) Effects of platelet-rich plasma gel on skin healing in surgical wound in horses. Acta Cir Bras 24:276

    Article  PubMed  Google Scholar 

  135. Findikcioglu F, Findikcioglu K, Yavuzer R, Lortlar N, Atabay K (2012) Effect of intraoperative platelet-rich plasma and fibrin glue application on skin flap survival. J Craniofac Surg 23:1513

    Article  PubMed  Google Scholar 

  136. Findikcioglu F, Findikcioglu K, Yavuzer R, Lortlar N, Atabay K (2012) Effect of preoperative subcutaneous platelet-rich plasma and fibrin glue application on skin flap survival. Aesthetic Plast Surg 36:1246

    Article  PubMed  Google Scholar 

  137. Pires Fraga MF, Nishio RT, Ishikawa RS, Perin LF, Helene A Jr, Malheiros CA (2010) Increased survival of free fat grafts with platelet-rich plasma in rabbits. J Plast Reconstr Aesthet Surg 63:e818

    Article  PubMed  Google Scholar 

  138. Shin HS, Oh HY (2012) The effect of platelet-rich plasma on wounds of OLETF Rats using expression of matrix metalloproteinase-2 and -9 mRNA. Arch Plast Surg 39:106

    Article  PubMed Central  PubMed  Google Scholar 

  139. Nakamura S, Ishihara M, Takikawa M, Murakami K, Kishimoto S, Yanagibayashi S et al (2010) Platelet-rich plasma (PRP) promotes survival of fat-grafts in rats. Ann Plast Surg 65:101

    Article  CAS  PubMed  Google Scholar 

  140. Gomez-Caro A, Ausin P, Boada M (2011) Platelet rich plasma improves the healing process after airway anastomosis. Interact Cardiovasc Thorac Surg 13:552

    Article  PubMed  Google Scholar 

  141. Balbo R, Avonto I, Marenchino D, Maddalena L, Menardi G, Peano G (2010) Platelet gel for the treatment of traumatic loss of finger substance. Blood Transfus 8:255

    PubMed Central  PubMed  Google Scholar 

  142. Chen TM, Tsai JC, Burnouf T (2010) A novel technique combining platelet gel, skin graft, and fibrin glue for healing recalcitrant lower extremity ulcers. Dermatol Surg: Off Publ Am Soc Dermatol Surg 36(4):453–460

    Article  CAS  Google Scholar 

  143. Yokota K, Ishida O, Sunagawa T, Suzuki O, Nakamae A, Ochi M (2008) Platelet-rich plasma accelerated surgical angio-genesis in vascular-implanted necrotic bone: an experimental study in rabbits. Acta Orthop 79:106

    Article  PubMed  Google Scholar 

  144. Serra R, Buffone G, Dominijanni A, Molinari V, Montemurro R, de Franciscis S (2013) Application of platelet-rich gel to enhance healing of transmetatarsal amputations in diabetic dysvascular patients. Int Wound J 10(5):612–615

    Article  PubMed  Google Scholar 

  145. Sell SA, Wolfe PS, Spence AJ, Rodriguez IA, McCool JM, Petrella RL et al (2012) A preliminary study on the potential of manuka honey and platelet-rich plasma in wound healing. Int J Biomater 2012:313781

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  146. de Leon JM, Driver VR, Fylling CP, Carter MJ, Anderson C, Wilson J et al (2011) The clinical relevance of treating chronic wounds with an enhanced near-physiological concentration of platelet-rich plasma gel. Adv Skin Wound Care 24:357

    Article  PubMed  Google Scholar 

  147. Frykberg RG, Driver VR, Carman D, Lucero B, Borris-Hale C, Fylling CP et al (2010) Chronic wounds treated with a physiologically relevant concentration of platelet-rich plasma gel: a prospective case series. Ostomy Wound Manage 56:36

    PubMed  Google Scholar 

  148. Cervelli V, Gentile P, De Angelis B, Calabrese C, Di Stefani A, Scioli MG et al (2011) Application of enhanced stromal vascular fraction and fat grafting mixed with PRP in post-traumatic lower extremity ulcers. Stem Cell Res 6:103

    Article  PubMed  Google Scholar 

  149. Bertrand-Duchesne MP, Grenier D, Gagnon G (2010) Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitro. J Periodontal Res 45:87

    Article  CAS  PubMed  Google Scholar 

  150. Guo S, Dipietro LA (2010) Factors affecting wound healing. J Dent Res 89:219

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  151. Notodihardjo FZ, Kakudo N, Kushida S, Suzuki K, Kusumoto K (2012) Bone regeneration with BMP-2 and hydroxyapatite in critical-size calvarial defects in rats. J Craniomaxillofac Surg 40:287

    Article  PubMed  Google Scholar 

  152. Li C, Kuchimanchi M, Hickman D, Poppe L, Hayashi M, Zhou Y et al (2009) In vitro metabolism of the novel, highly selective oral angiogenesis inhibitor motesanib diphosphate in preclinical species and in humans. Drug Metab Dispos 37:1378

    Article  CAS  PubMed  Google Scholar 

  153. Almdahl SM, Veel T, Halvorsen P, Vold MB, Molstad P (2011) Randomized prospective trial of saphenous vein harvest site infection after wound closure with and without topical application of autologous platelet-rich plasma. Eur J Cardiothorac Surg 39:44

    Article  PubMed  Google Scholar 

  154. Drago L, Bortolin M, Vassena C, Taschieri S, Del Fabbro M (2013) Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity. BMC Microbiol 13:47

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  155. Li H, Li B (2013) PRP as a new approach to prevent infection: preparation and in vitro antimicrobial properties of PRP. J Vis Exp. doi:10.3791/50351

  156. Tohidnezhad M, Varoga D, Podschun R, Wruck CJ, Seekamp A, Brandenburg LO et al (2011) Thrombocytes are effectors of the innate immune system releasing human beta defensin-3. Injury 42:682

    Article  PubMed  Google Scholar 

  157. Toba T, Nakamura T, Matsumoto K, Fukuda S, Yoshitani M, Ueda H et al (2002) Influence of dehydrothermal crosslinking on the growth of PC-12 cells cultured on laminin coated collagen. ASAIO J 48:17

    Article  PubMed  Google Scholar 

  158. Kulbatski I, Mothe AJ, Nomura H, Tator CH (2005) Endogenous and exogenous CNS derived stem/progenitor cell approaches for neurotrauma. Curr Drug Targets 6:111

    Article  CAS  PubMed  Google Scholar 

  159. Kuo SP (2008) Plasma assisted decontamination of bacterial spores. Open Biomed Eng J 2:36

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  160. Tohidnezhad M, Varoga D, Wruck CJ, Podschun R, Sachweh BH, Bornemann J et al (2012) Platelets display potent antimicrobial activity and release human beta-defensin 2. Platelets 23:217

    Article  CAS  PubMed  Google Scholar 

  161. Fadeyi E, Adams S, Peterson B, Hackett J, Byrne P, Klein HG et al (2008) Analysis of a high-throughput HLA antibody screening assay for use with platelet donors. Transfusion 48:1174

    Article  PubMed Central  PubMed  Google Scholar 

  162. Rozalski MI, Micota B, Sadowska B, Paszkiewicz M, Wieckowska-Szakiel M, Rozalska B (2013) Antimicrobial/anti-biofilm activity of expired blood platelets and their released products. Postepy Hig Med Dosw (Online) 67:321

    Article  Google Scholar 

  163. Tyner TR, Parks N, Faria S, Simons M, Stapp B, Curtis B et al (2007) Effects of collagen nerve guide on neuroma formation and neuropathic pain in a rat model. Am J Surg 193:e1

    Article  PubMed  Google Scholar 

  164. Coderre TJ, Grimes RW, Melzack R (1986) Deafferentation and chronic pain in animals: an evaluation of evidence suggesting autotomy is related to pain. Pain 26:61

    Article  CAS  PubMed  Google Scholar 

  165. Kauppila T (1998) Correlation between autotomy-behavior and current theories of neuropathic pain. Neurosci Biobehav Rev 23:111

    Article  CAS  PubMed  Google Scholar 

  166. Geddis AE (2009) The regulation of proplatelet production. Haematologica 94:756

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  167. Krogh TP, Fredberg U, Stengaard-Pedersen K, Christensen R, Jensen P, Ellingsen T (2013) Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med 41:625

    Article  PubMed  Google Scholar 

  168. Kesikburun S, Tan AK, Yilmaz B, Yasar E, Yazicioglu K (2013) Platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a randomized controlled trial with 1-year follow-up. Am J Sports Med 41:2609

    Article  PubMed  Google Scholar 

  169. Boswell SG, Schnabel LV, Mohammed HO, Sundman EA, Minas T, Fortier LA (2013) Increasing platelet concentrations in leukocyte-reduced platelet-rich plasma decrease collagen gene synthesis in tendons. Am J Sports Med 42(1):42–49

    Article  PubMed  Google Scholar 

  170. Aggarwal AK, Shashikanth VS, Marwaha N (2014) Platelet-rich plasma prevents blood loss and pain and enhances early functional outcome after total knee arthroplasty: a prospective randomised controlled study. Int Orthop 38(2):387–395

    Article  PubMed Central  PubMed  Google Scholar 

  171. Hechtman KS, Uribe JW, Botto-vanDemden A, Kiebzak GM (2011) Platelet-rich plasma injection reduces pain in patients with recalcitrant epicondylitis. Orthopedics 34:92

    PubMed  Google Scholar 

  172. Cordoba-Fernandez A, Rayo-Rosado R, Juarez-Jimenez JM (2010) The use of autologous platelet gel in toenail surgery: a within-patient clinical trial. Open Biomed Eng J : Off Publ Am Coll Foot Ankle Surg 49:385

    Google Scholar 

  173. Zhang C, Sun A, Zhang P, Wu C, Zhang S, Fu M et al (2010) Aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract 87:211

    Article  CAS  PubMed  Google Scholar 

  174. Thanasas C, Papadimitriou G, Charalambidis C, Paraskevopoulos I, Papanikolaou A (2011) Platelet-rich plasma versus autologous whole blood for the treatment of chronic lateral elbow epicondylitis: a randomized controlled clinical trial. Am J Sports Med 39:2130

    Article  PubMed  Google Scholar 

  175. Finnoff JT, Fowler SP, Lai JK, Santrach PJ, Willis EA, Sayeed YA et al (2011) Treatment of chronic tendinopathy with ultrasound-guided needle tenotomy and platelet-rich plasma injection. PM & R : J Inj Funct Rehabil 3:900

    Article  Google Scholar 

  176. Gosens T, Peerbooms JC, van Laar W, den Oudsten BL (2011) 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 39:1200

    Article  PubMed  Google Scholar 

  177. Sanchez M, Guadilla J, Fiz N, Andia I (2012) Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip. Rheumatology 51:144

    Article  CAS  PubMed  Google Scholar 

  178. Rha DW, Park GY, Kim YK, Kim MT, Lee SC (2013) Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: a randomized controlled trial. Clin Rehabil 27:113

    Article  PubMed  Google Scholar 

  179. Santiago-Figueroa J, Kuffler DP (2009) Reducing and eliminating neuropathic pain. P R Health Sci J 28:289

    PubMed  Google Scholar 

  180. Kuffler DP (2011) A novel technique for reducing and eliminating peripheral neuropathic pain: a clinical study. J Pain Manag 4:386

    Google Scholar 

  181. Kuffler DP, Reyes O, Sosa IJ, Santiago-Figueroa J (2011) Neurological recovery across a 12-cm-long ulnar nerve gap repaired 3.25 years post trauma: case report. Neurosurgery 69:E1321

    Article  PubMed  Google Scholar 

  182. Kim CF, Moalem-Taylor G (2011) Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice. J Pain : Off J Am Pain Soc 12:370

    Article  CAS  Google Scholar 

  183. Benninger M, Walner D (2007) Coblation: improving outcomes for children following adenotonsillectomy. Clin Cornerstone 9(1):S13

    Article  PubMed  Google Scholar 

  184. Nadeau S, Filali M, Zhang J, Kerr BJ, Rivest S, Soulet D et al (2011) Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1beta and TNF: implications for neuropathic pain. J Neurosci : Off J Soc Neurosci 31:12533

    Article  CAS  Google Scholar 

  185. Kanno T, Takahashi T, Tsujisawa T, Ariyoshi W, Nishihara T (2005) Platelet-rich plasma enhances human osteoblast-like cell proliferation and differentiation. J Oral Maxillofac Surg 63:362

    Article  PubMed  Google Scholar 

  186. 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

    Article  PubMed  Google Scholar 

  187. Scudeller L, Del Fante C, Perotti C, Pavesi CF, Coscia D, Scotti V et al (2011) N of 1, two contemporary arm, randomised controlled clinical trial for bilateral epicondylitis: a new study design. BMJ 343:d7653

    Article  PubMed Central  PubMed  Google Scholar 

  188. Li M, Zhang C, Ai Z, Yuan T, Feng Y, Jia W (2011) Therapeutic effectiveness of intra-knee-articular injection of platelet-rich plasma on knee articular cartilage degeneration. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chin J Rep Reconstr Surg 25:1192

    Google Scholar 

  189. Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A et al (2011) Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy : J Arthrosc Relat Surg : Off Publ Arthroscopy Assoc North America Int Arthroscopy Assoc 27:1490

    Article  Google Scholar 

  190. Andia I, Sanchez M, Maffulli N (2011) Platelet rich plasma therapies for sports muscle injuries: any evidence behind clinical practice? Expert Opin Biol Ther 11:509

    Article  PubMed  Google Scholar 

  191. Andia I, Sanchez M, Maffulli N (2012) Joint pathology and platelet-rich plasma therapies. Expert Opin Biol Ther 12:7

    Article  CAS  PubMed  Google Scholar 

  192. Bava ED, Barber FA (2011) Platelet-rich plasma products in sports medicine. Phys Sportsmed 39:94

    Article  PubMed  Google Scholar 

  193. Araki J, Jona M, Eto H, Aoi N, Kato H, Suga H et al (2012) Optimized preparation method of platelet-concentrated plasma and noncoagulating platelet-derived factor concentrates: maximization of platelet concentration and removal of fibrinogen. Tissue engineering. Part C Methods 18:176

    Article  CAS  Google Scholar 

  194. Yu W, Wang J, Yin J (2011) Platelet-rich plasma: a promising product for treatment of peripheral nerve regeneration after nerve injury. Int J Neurosci 121(4):176–180

    Article  PubMed  Google Scholar 

  195. Hibner M, Castellanos ME, Drachman D, Balducci J (2012) Repeat operation for treatment of persistent pudendal nerve entrapment after pudendal neurolysis. J Minim Invasive Gynecol 19:325

    Article  PubMed  Google Scholar 

  196. Semenov FV, Iakobashvili I (2007) Usage of platelet-enriched plasma as hemostatic and analgenic medication in tonsillectomy. Vestn Otorinolaringol (6):48–50

  197. Maffulli N, Del Buono A (2012) Platelet plasma rich products in musculoskeletal medicine: any evidence? Surgeon 10:148

    Article  PubMed  Google Scholar 

  198. Cinotti G, Corsi A, Sacchetti B, Riminucci M, Bianco P, Giannicola G (2013) Bone ingrowth and vascular supply in experimental spinal fusion with platelet-rich plasma. Spine (Phila Pa 1976) 38:385

    Article  Google Scholar 

  199. Mammoto T, Jiang A, Jiang E, Mammoto A (2013) Platelet rich plasma extract promotes angiogenesis through the angiopoietin1-Tie2 pathway. Microvasc Res 89:15

    Article  CAS  PubMed  Google Scholar 

  200. Kurita J, Miyamoto M, Ishii Y, Aoyama J, Takagi G, Naito Z et al (2011) Enhanced vascularization by controlled release of platelet-rich plasma impregnated in biodegradable gelatin hydrogel. Ann Thorac Surg 92:837

    Article  PubMed  Google Scholar 

  201. Bir SC, Esaki J, Marui A, Yamahara K, Tsubota H, Ikeda T et al (2009) Angiogenic properties of sustained release platelet-rich plasma: characterization in-vitro and in the ischemic hind limb of the mouse. J Vasc Surg 50:870

    Article  PubMed  Google Scholar 

  202. Dong Z, Li B, Liu B, Bai S, Li G, Ding A et al (2012) Platelet-rich plasma promotes angiogenesis of prefabricated vascularized bone graft. J Oral Maxillofac Surg 70:2191

    Article  PubMed  Google Scholar 

  203. Moreira DC, Sa CN, Andrade MG, Borio dos Santos Calmon de Bittencourt TC, de Almeida Reis SR, Pithon MM et al (2013) Angiogenesis and osteogenesis at incorporation process of onlay bone graft. J Oral Maxillofac Surg 71:2048

  204. Horimizu M, Kawase T, Nakajima Y, Okuda K, Nagata M, Wolff LF et al (2013) An improved freeze-dried PRP-coated biodegradable material suitable for connective tissue regenerative therapy. Cryobiology 66:223

    Article  CAS  PubMed  Google Scholar 

  205. Farrior E, Ladner K (2011) Platelet gels and hemostasis in facial plastic surgery. Facial Plast Surg 27:308

    Article  CAS  PubMed  Google Scholar 

  206. Betsch M, Schneppendahl J, Thuns S, Herten M, Sager M, Jungbluth P et al (2013) Bone marrow aspiration concentrate and platelet rich plasma for osteochondral repair in a porcine osteochondral defect model. PLoS One 8:e71602

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  207. Kim ES, Kim JJ, Park EJ (2010) Angiogenic factor-enriched platelet-rich plasma enhances in vivo bone formation around alloplastic graft material. J Adv Prosthodont 2:7

    Article  PubMed Central  PubMed  Google Scholar 

  208. Roy S, Driggs J, Elgharably H, Biswas S, Findley M, Khanna S et al (2011) Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation. Wound Repair Regen: official publication of the Wound Healing Society [and] the European Tissue Repair 19:753

    Article  Google Scholar 

  209. Oh DS, Cheon YW, Jeon YR, Lew DH (2011) Activated platelet-rich plasma improves fat graft survival in nude mice: a pilot study. Dermatol Surg 37:619

    Article  CAS  PubMed  Google Scholar 

  210. Rodriguez-Flores J, Palomar-Gallego MA, Enguita-Valls AB, Rodriguez-Peralto JL, Torres J (2011) Influence of platelet-rich plasma on the histologic characteristics of the autologous fat graft to the upper lip of rabbits. Aesthetic Plast Surg 35:480

    Article  PubMed  Google Scholar 

  211. Salgarello M, Visconti G, Rusciani A (2011) Breast fat grafting with platelet-rich plasma: a comparative clinical study and current state of the art. Plast Reconstr Surg 127:2176

    Article  CAS  PubMed  Google Scholar 

  212. Gentile P, Di Pasquali C, Bocchini I, Floris M, Eleonora T, Fiaschetti V et al (2013) Breast reconstruction with autologous fat graft mixed with platelet-rich plasma. Surg Innov 20:370

    Article  PubMed  Google Scholar 

  213. Jin R, Zhang L, Zhang YG (2013) Does platelet-rich plasma enhance the survival of grafted fat? An update review. Int J Clin Exp Med 6:252

    PubMed Central  PubMed  Google Scholar 

  214. Willemsen JC, Lindenblatt N, Stevens HP (2013) Results and long-term patient satisfaction after gluteal augmentation with platelet-rich plasma-enriched autologous fat. Eur J Plast Surg 36:777

    Article  PubMed Central  PubMed  Google Scholar 

  215. Sariguney Y, Yavuzer R, Elmas C, Yenicesu I, Bolay H, Atabay K (2008) Effect of platelet-rich plasma on peripheral nerve regeneration. J Reconstr Microsurg 24:159

    Article  PubMed  Google Scholar 

  216. Piskin A, Kaplan S, Aktas A, Ayyildiz M, Raimondo S, Alic T et al (2009) Platelet gel does not improve peripheral nerve regeneration: an electrophysiological, stereological, and electron microscopic study. Microsurgery 29:144

    Article  PubMed  Google Scholar 

  217. Kaplan S, Piskin A, Ayyildiz M, Aktas A, Koksal B, Ulkay MB et al (2011) The effect of melatonin and platelet gel on sciatic nerve repair: an electrophysiological and stereological study. Microsurgery 31:306

    Article  PubMed  Google Scholar 

  218. Hiraizumi Y, Fujimaki E, Transfeldt EE, Kawahara N, Fiegel VD, Knighton D et al (1996) The effect of the platelet derived wound healing formula and the nerve growth factor on the experimentally injured spinal cord. Spinal Cord 34:394

    Article  CAS  PubMed  Google Scholar 

  219. Elgazzar RF, Mutabagani MA, Abdelaal SE, Sadakah AA (2008) Platelet rich plasma may enhance peripheral nerve regeneration after cyanoacrylate reanastomosis: a controlled blind study on rats. Int J Oral Maxillofac Surg 37:748

    Article  CAS  PubMed  Google Scholar 

  220. Ding XG, Li SW, Zheng XM, Hu LQ, Hu WL, Luo Y (2009) The effect of platelet-rich plasma on cavernous nerve regeneration in a rat model. Asian J Androl 11:215

    Article  PubMed Central  PubMed  Google Scholar 

  221. Cho HH, Jang S, Lee SC, Jeong HS, Park JS, Han JY et al (2010) Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model. Laryngoscope 120:907

    Article  CAS  PubMed  Google Scholar 

  222. Sabongi RG, De Rizzo LA, Fernandes M, Valente SG, Gomes dos Santos JB, Faloppa F et al (2014) Nerve regeneration: is there an alternative to nervous graft? J Reconstr Microsurg 30:607

    Article  PubMed  Google Scholar 

  223. Zheng C, Zhu Q, Liu X, Huang X, He C, Jiang L et al (2014) Improved peripheral nerve regeneration using acellular nerve allografts loaded with platelet-rich plasma. Tissue Eng Part A 20:3228

    Article  PubMed  PubMed Central  Google Scholar 

  224. Dagum AB (1998) Peripheral nerve regeneration, repair, and grafting. J Hand Ther 11:111

    Article  CAS  PubMed  Google Scholar 

  225. Menovsky T, van Overbeeke JJ (1997) Full functional recovery after surgical repair of transected abducens nerve: case report. Neurosurgery 41:998

    Article  CAS  PubMed  Google Scholar 

  226. Murray JA, Mountain R, Willins M (1994) Best method for facial nerve anastomosis. Eur Arch Otorhinolaryngol:S416

  227. Kalbermatten DF, Pettersson J, Kingham PJ, Pierer G, Wiberg M, Terenghi G (2009) New fibrin conduit for peripheral nerve repair. J Reconstr Microsurg 25:27

    Article  PubMed  Google Scholar 

  228. Palazzi S, Vila-Torres J, Lorenzo JC (1995) Fibrin glue is a sealant and not a nerve barrier. J Reconstr Microsurg 11:135

    Article  CAS  PubMed  Google Scholar 

  229. Zeng L, Huck S, Redl H, Schlag G (1995) Fibrin sealant matrix supports outgrowth of peripheral sensory axons. Scand J Plast Reconstr Surg Hand Surg 29:199

    Article  CAS  PubMed  Google Scholar 

  230. Pettersson J, Kalbermatten D, McGrath A, Novikova LN (2010) Biodegradable fibrin conduit promotes long-term regeneration after peripheral nerve injury in adult rats. J Plast Reconstr Aesthet Surg 63(11):1893–1899

    Article  PubMed  Google Scholar 

  231. Lee AC, Yu VM, Lowe JB 3rd, Brenner MJ, Hunter DA, Mackinnon SE et al (2003) Controlled release of nerve growth factor enhances sciatic nerve regeneration. Exp Neurol 184:295

    Article  CAS  PubMed  Google Scholar 

  232. Galla TJ, Vedecnik SV, Halbgewachs J, Steinmann S, Friedrich C, Stark GB (2004) Fibrin/Schwann cell matrix in poly-epsilon-caprolactone conduits enhances guided nerve regeneration. Int J Artif Organs 27:127

    CAS  PubMed  Google Scholar 

  233. Povlsen B (1994) A new fibrin seal in primary repair of peripheral nerves. J Hand Surg (Br) 19:43

    Article  CAS  Google Scholar 

  234. Gao C, Ma S, Ji Y, Wang JE, Li J (2008) Siatic nerve regeneration in rats stimulated by fibrin glue containing nerve growth factor: an experimental study. Injury 39:1414

    Article  PubMed  Google Scholar 

  235. Johnson PJ, Tatara A, Shiu A, Sakiyama-Elbert SE (2010) Controlled release of neurotrophin-3 and platelet-derived growth factor from fibrin scaffolds containing neural progenitor cells enhances survival and differentiation into neurons in a subacute model of SCI. Cell Transplant 19:89

    Article  PubMed Central  PubMed  Google Scholar 

  236. Willerth SM, Rader A, Sakiyama-Elbert SE (2008) The effect of controlled growth factor delivery on embryonic stem cell differentiation inside fibrin scaffolds. Stem Cell Res 1:205

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  237. Wood MD, Moore AM, Hunter DA, Tuffaha S, Borschel GH, Mackinnon SE et al (2009) Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration. Acta Biomater 5:959

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  238. Emel E, Ergun SS, Kotan D, Gursoy EB, Parman Y, Zengin A et al (2011) Effects of insulin-like growth factor-I and platelet-rich plasma on sciatic nerve crush injury in a rat model. J Neurosurg 114:522

    Article  CAS  PubMed  Google Scholar 

  239. Reyes O, Sosa IJ, Santiago J, Kuffler DP (2007) A novel technique leading to complete sensory and motor recovery across a long peripheral nerve gap. P R Health Sci J 26:225

    PubMed  Google Scholar 

  240. Reyes O, Sosa I, Kuffler DP (2005) Promoting neurological recovery following a traumatic peripheral nerve injury. P R Health Sci J 24:215

    PubMed  Google Scholar 

  241. Kuffler DP (2014) An assessment of current techniques for inducing axon regeneration and neurological recovery following peripheral nerve trauma. Prog Neurobiol 116:1

    Article  PubMed  Google Scholar 

  242. Anjayani S, Wirohadidjojo YW, Adam AM, Suwandi D, Seweng A, Amiruddin MD (2014) Sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma. Int J Dermatol 53:109

    Article  CAS  PubMed  Google Scholar 

  243. Takeuchi M, Kamei N, Shinomiya R, Sunagawa T, Suzuki O, Kamoda H et al (2012) Human platelet-rich plasma promotes axon growth in brain-spinal cord coculture. Neuroreport 23:712

    Article  PubMed  Google Scholar 

  244. Shen YX, Fan ZH, Zhao JG, Zhang P (2009) The application of platelet-rich plasma may be a novel treatment for central nervous system diseases. Med Hypotheses 73:1038

    Article  CAS  PubMed  Google Scholar 

  245. Mligiliche NL, Tabata Y, Ide C (1999) Nerve regeneration through biodegradable gelatin conduits in mice. East Afr Med J 76:400

    CAS  PubMed  Google Scholar 

  246. Ogata T, Yamamoto S, Nakamura K, Tanaka S (2006) Signaling axis in Schwann cell proliferation and differentiation. Mol Neurobiol 33:51

    Article  CAS  PubMed  Google Scholar 

  247. Monje PV, Rendon S, Athauda G, Bates M, Wood PM, Bunge MB (2009) Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation. Glia 57:947

    Article  PubMed Central  PubMed  Google Scholar 

  248. Oya T, Zhao YL, Takagawa K, Kawaguchi M, Shirakawa K, Yamauchi T et al (2002) Platelet-derived growth factor-b expression induced after rat peripheral nerve injuries. Glia 38:303

    Article  PubMed  Google Scholar 

  249. Tohill M, Mantovani C, Wiberg M, Terenghi G (2004) Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett 362:200

    Article  CAS  PubMed  Google Scholar 

  250. Kalbermatten DF, Kingham PJ, Mahay D, Mantovani C, Pettersson J, Raffoul W et al (2008) Fibrin matrix for suspension of regenerative cells in an artificial nerve conduit. J Plast Reconstr Aesthet Surg 61:669

    Article  CAS  PubMed  Google Scholar 

  251. Mantovani C, Terenghi G, Shawcross SG (2012) Isolation of adult stem cells and their differentiation to Schwann cells. Methods Mol Biol 916:47

    Article  CAS  PubMed  Google Scholar 

  252. Tomita K, Madura T, Mantovani C, Terenghi G (2012) Differentiated adipose-derived stem cells promote myelination and enhance functional recovery in a rat model of chronic denervation. J Neurosci Res 90:1392

    Article  CAS  PubMed  Google Scholar 

  253. Waniczek D, Kozowicz A, Muc-Wierzgon M, Kokot T, Swietochowska E, Nowakowska-Zajdel E (2013) Adjunct methods of the standard diabetic foot ulceration therapy. Evid Based Complement Alternat Med 2013:243568

    Article  PubMed Central  PubMed  Google Scholar 

  254. Goto E, Mukozawa M, Mori H, Hara M (2010) A rolled sheet of collagen gel with cultured Schwann cells: model of nerve conduit to enhance neurite growth. J Biosci Bioeng 109:512

    Article  CAS  PubMed  Google Scholar 

  255. Pan HC, Chen CJ, Cheng FC, Ho SP, Liu MJ, Hwang SM et al (2009) Combination of G-CSF administration and human amniotic fluid mesenchymal stem cell transplantation promotes peripheral nerve regeneration. Neurochem Res 34:518

    Article  CAS  PubMed  Google Scholar 

  256. Liu GB, Cheng YX, Feng YK, Pang CJ, Li Q, Wang Y et al (2011) Adipose-derived stem cells promote peripheral nerve repair. Arch Med Sci 7:592

    Article  PubMed Central  PubMed  Google Scholar 

  257. Zwezdaryk KJ, Coffelt SB, Figueroa YG, Liu J, Phinney DG, LaMarca HL et al (2007) Erythropoietin, a hypoxia-regulated factor, elicits a pro-angiogenic program in human mesenchymal stem cells. Exp Hematol 35:640

    Article  CAS  PubMed  Google Scholar 

  258. Zuo J, Neubauer D, Dyess K, Ferguson TA, Muir D (1998) Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue. Exp Neurol 154:654

    Article  CAS  PubMed  Google Scholar 

  259. Zuo J, Hernandez YJ, Muir D (1998) Chondroitin sulfate proteoglycan with neurite-inhibiting activity is up-regulated following peripheral nerve injury. J Neurobiol 34:41

    Article  CAS  PubMed  Google Scholar 

  260. Heine W, Conant K, Griffin JW, Hoke A (2004) Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves. Exp Neurol 189:231

    Article  CAS  PubMed  Google Scholar 

  261. Ding Y, Yan Q, Ruan JW, Zhang YQ, Li WJ, Zeng X et al (2013) Electroacupuncture promotes the differentiation of transplanted bone marrow mesenchymal stem cells overexpressing TrkC into neuron-like cells in transected spinal cord of rats. Cell Transplant 22:65

    Article  PubMed  Google Scholar 

  262. Lundborg G, Dahlin LB, Danielsen N, Hansson HA, Johannesson A, Longo FM et al (1982) Nerve regeneration across an extended gap: a neurobiological view of nerve repair and the possible involvement of neuronotrophic factors. J Hand Surg [Am] 7:580

    Article  CAS  Google Scholar 

  263. Williams LR (1987) Exogenous fibrin matrix precursors stimulate the temporal progress of nerve regeneration within a silicone chamber. Neurochem Res 12:851

    Article  CAS  PubMed  Google Scholar 

  264. Williams LR, Danielsen N, Muller H, Varon S (1987) Exogenous matrix precursors promote functional nerve regeneration across a 15-mm gap within a silicone chamber in the rat. J Comp Neurol 264:284

    Article  CAS  PubMed  Google Scholar 

  265. Williams LR, Powell HC, Lundborg G, Varon S (1984) Competence of nerve tissue as distal insert promoting nerve regeneration in a silicone chamber. Brain Res 293:201

    Article  CAS  PubMed  Google Scholar 

  266. Williams LR, Varon S (1985) Modification of fibrin matrix formation in situ enhances nerve regeneration in silicone chambers. J Comp Neurol 231:209

    Article  CAS  PubMed  Google Scholar 

  267. Lundborg G, Dahlin LB, Danielsen NP, Hansson HA, Larsson K (1981) Reorganization and orientation of regenerating nerve fibres, perineurium, and epineurium in preformed mesothelial tubes—an experimental study on the sciatic nerve of rats. J Neurosci Res 6:265

    Article  CAS  PubMed  Google Scholar 

  268. Mackinnon SE, Dellon AL (1988) A comparison of nerve regeneration across a sural nerve graft and a vascularized pseudosheath. J Hand Surg [Am] 13:935

    Article  CAS  Google Scholar 

  269. Mackinnon SE, Dellon AL (1990) Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube. Plast Reconstr Surg 85:419

    Article  CAS  PubMed  Google Scholar 

  270. Mackinnon SE, Dellon AL (1992) Reinnervation of distal sensory nerve environments by regenerating sensory axons. Neuroscience 46:595

    Article  CAS  PubMed  Google Scholar 

  271. Kuffler DP (1987) Long-distance regulation of regenerating frog axons. J Exp Biol 132:151

    CAS  PubMed  Google Scholar 

  272. Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA (2010) Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med 5:933

    Article  PubMed Central  PubMed  Google Scholar 

  273. Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG (2006) Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 198:54

    Article  CAS  PubMed  Google Scholar 

  274. Park HW, Lim MJ, Jung H, Lee SP, Paik KS, Chang MS (2010) Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury. Glia 58:1118

    Article  PubMed  Google Scholar 

  275. Ao Q, Fung CK, Tsui AY, Cai S, Zuo HC, Chan YS et al (2011) The regeneration of transected sciatic nerves of adult rats using chitosan nerve conduits seeded with bone marrow stromal cell-derived Schwann cells. Biomaterials 32:787

    Article  CAS  PubMed  Google Scholar 

  276. Dadon-Nachum M, Sadan O, Srugo I, Melamed E, Offen D (2011) Differentiated mesenchymal stem cells for sciatic nerve injury. Stem Cell Rev 7:664

    Article  PubMed  Google Scholar 

  277. Satar B, Hidir Y, Serdar MA, Kucuktag Z, Ural AU, Avcu F et al (2012) Protein profiling of anastomosed facial nerve treated with mesenchymal stromal cells. Cytotherapy 14(5):522–528

    Article  CAS  PubMed  Google Scholar 

  278. Fuhrmann T, Montzka K, Hillen LM, Hodde D, Dreier A, Bozkurt A et al (2010) Axon growth-promoting properties of human bone marrow mesenchymal stromal cells. Neurosci Lett 474:37

    Article  PubMed  CAS  Google Scholar 

  279. Pei YY, Duan SB, Cai WJ, Yi XN, Zeng ZC, Zhang JW et al (2005) Effects of transforming growth factor-beta 1 on the peripheral nerve regeneration of rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban 30:447

    CAS  PubMed  Google Scholar 

  280. Oliveira JT, Almeida FM, Biancalana A, Baptista AF, Tomaz MA, Melo PA et al (2010) Mesenchymal stem cells in a polycaprolactone conduit enhance median-nerve regeneration, prevent decrease of creatine phosphokinase levels in muscle, and improve functional recovery in mice. Neuroscience 170:1295

    Article  CAS  PubMed  Google Scholar 

  281. Ladak A, Olson J, Tredget EE, Gordon T (2011) Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model. Exp Neurol 228:242

    Article  CAS  PubMed  Google Scholar 

  282. di Summa PG, Kalbermatten DF, Pralong E, Raffoul W, Kingham PJ, Terenghi G (2011) Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts. Neuroscience 181:278

    Article  PubMed  CAS  Google Scholar 

  283. Bumol TF, Walker LE, Reisfeld RA (1984) Biosynthetic studies of proteoglycans in human melanoma cells with a monoclonal antibody to a core glycoprotein of chondroitin sulfate proteoglycans. J Biol Chem 259:12733

    CAS  PubMed  Google Scholar 

  284. McGrath AM, Brohlin M, Kingham PJ, Novikov LN, Wiberg M, Novikova LN (2012) Fibrin conduit supplemented with human mesenchymal stem cells and immunosuppressive treatment enhances regeneration after peripheral nerve injury. Neurosci Lett 516:171

    Article  CAS  PubMed  Google Scholar 

  285. Liu C, Zhang J (1995) Acute cholangitis due to bile duct stones: clinical analysis of 85 cases. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 17:461

    CAS  PubMed  Google Scholar 

  286. Coppinger JA, Maguire PB (2007) Insights into the platelet releasate. Curr Pharm Des 13:2640

    Article  CAS  PubMed  Google Scholar 

  287. Yabanoglu S, Akkiki M, Seguelas MH, Mialet-Perez J, Parini A, Pizzinat N (2009) Platelet derived serotonin drives the activation of rat cardiac fibroblasts by 5-HT2A receptors. J Mol Cell Cardiol 46:518

    Article  CAS  PubMed  Google Scholar 

  288. Joung I, Yoo M, Woo JH, Chang CY, Heo H, Kwon YK (2010) Secretion of EGF-like domain of heregulinbeta promotes axonal growth and functional recovery of injured sciatic nerve. Mol Cells 30:477

    Article  CAS  PubMed  Google Scholar 

  289. Tsai NP, Tsui YC, Pintar JE, Loh HH, Wei LN (2010) Kappa opioid receptor contributes to EGF-stimulated neurite extension in development. Proc Natl Acad Sci U S A 107:3216

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  290. Hermann PM, Nicol JJ, Nagle GT, Bulloch AG, Wildering WC (2005) Epidermal growth factor-dependent enhancement of axonal regeneration in the pond snail Lymnaea stagnalis: role of phagocyte survival. J Comp Neurol 492:383

    Article  CAS  PubMed  Google Scholar 

  291. Goldshmit Y, Greenhalgh CJ, Turnley AM (2004) Suppressor of cytokine signalling-2 and epidermal growth factor regulate neurite outgrowth of cortical neurons. Eur J Neurosci 20:2260

    Article  PubMed  Google Scholar 

  292. Brinkmann BG, Agarwal A, Sereda MW, Garratt AN, Muller T, Wende H et al (2008) Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. Neuron 59:581

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  293. Cornejo M, Nambi D, Walheim C, Somerville M, Walker J, Kim L et al (2010) Effect of NRG1, GDNF, EGF and NGF in the migration of a Schwann cell precursor line. Neurochem Res 35:1643

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  294. Xian CJ, Zhou XF (1999) Roles of transforming growth factor-alpha and related molecules in the nervous system. Mol Neurobiol 20:157

    Article  CAS  PubMed  Google Scholar 

  295. Ortega MC, Bribian A, Peregrin S, Gil MT, Marin O, de Castro F (2012) Neuregulin-1/ErbB4 signaling controls the migration of oligodendrocyte precursor cells during development. Exp Neurol 235:610

    Article  CAS  PubMed  Google Scholar 

  296. Newbern J, Birchmeier C (2010) Nrg1/ErbB signaling networks in Schwann cell development and myelination. Semin Cell Dev Biol 21:922

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  297. Yamazaki T, Sabit H, Oya T, Ishii Y, Hamashima T, Tokunaga A et al (2009) Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves. J Peripher Nerv Syst 14:165

    Article  CAS  PubMed  Google Scholar 

  298. Hermanson M, Olsson T, Westermark B, Funa K (1995) PDGF and its receptors following facial nerve axotomy in rats: expression in neurons and surrounding glia. Exp Brain Res 102:415

    Article  CAS  PubMed  Google Scholar 

  299. Oudega M, Xu XM, Guenard V, Kleitman N, Bunge MB (1997) A combination of insulin-like growth factor-I and platelet-derived growth factor enhances myelination but diminishes axonal regeneration into Schwann cell grafts in the adult rat spinal cord. Glia 19:247

    Article  CAS  PubMed  Google Scholar 

  300. Cheng HL, Russell JW, Feldman EL (1999) IGF-I promotes peripheral nervous system myelination. Ann N Y Acad Sci 883:124

    Article  CAS  PubMed  Google Scholar 

  301. Liang G, Cline GW, Macica CM (2007) IGF-1 stimulates de novo fatty acid biosynthesis by Schwann cells during myelination. Glia 55:632

    Article  PubMed  Google Scholar 

  302. Sondell M, Fex-Svenningsen A, Kanje M (1997) The insulin-like growth factors I and II stimulate proliferation of different types of Schwann cells. Neuroreport 8:2871

    Article  CAS  PubMed  Google Scholar 

  303. Fex Svenningsen A, Kanje M (1996) Insulin and the insulin-like growth factors I and II are mitogenic to cultured rat sciatic nerve segments and stimulate [3H]thymidine incorporation through their respective receptors. Glia 18:68

    Article  PubMed  Google Scholar 

  304. Cheng HL, Feldman EL (1997) Insulin-like growth factor-I (IGF-I) and IGF binding protein-5 in Schwann cell differentiation. J Cell Physiol 171:161

    Article  CAS  PubMed  Google Scholar 

  305. Thompson JS, Kampfe PW, Newland JR, Vanderhoof JA (1986) Growth of intestinal neomucosa on prosthetic materials. J Surg Res 41:484

    Article  CAS  PubMed  Google Scholar 

  306. Siemionow M, Bozkurt M, Zor F (2010) Regeneration and repair of peripheral nerves with different biomaterials: review. Microsurgery 30:574

    Article  PubMed  Google Scholar 

  307. Nasir S, Krokowicz L, Bozkurt M, Siemionow M (2008) Inlay technique for large skin graft replacement in the small animal. Plast Reconstr Surg 122:167e

    Article  PubMed  Google Scholar 

  308. Hoke A, Sun HS, Gordon T, Zochodne DW (2001) Do denervated peripheral nerve trunks become ischemic? The impact of chronic denervation on vasa nervorum. Exp Neurol 172:398

    Article  CAS  PubMed  Google Scholar 

  309. Hobson MI, Green CJ, Terenghi G (2000) VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J Anat 197(Pt 4):591

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  310. Hou SY, Zhang HY, Quan DP, Liu XL, Zhu JK (2006) Tissue-engineered peripheral nerve grafting by differentiated bone marrow stromal cells. Neuroscience 140:101

    Article  CAS  PubMed  Google Scholar 

  311. Kokai LE, Bourbeau D, Weber D, McAtee J, Marra KG (2011) Sustained growth factor delivery promotes axonal regeneration in long gap peripheral nerve repair. Tissue Eng Part A 17:1263

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  312. Pale T, Frisch EB, McClellan AD (2013) Cyclic AMP stimulates neurite outgrowth of lamprey reticulospinal neurons without substantially altering their biophysical properties. Neuroscience 245:74

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  313. Cui Q, Yip HK, Zhao RC, So KF, Harvey AR (2003) Intraocular elevation of cyclic AMP potentiates ciliary neurotrophic factor-induced regeneration of adult rat retinal ganglion cell axons. Mol Cell Neurosci 22:49

    Article  CAS  PubMed  Google Scholar 

  314. Gordon T (2009) The role of neurotrophic factors in nerve regeneration. Neurosurg Focus 26:E3

    Article  PubMed  Google Scholar 

  315. Gao Y, Nikulina E, Mellado W, Filbin MT (2003) Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. J Neurosci 23:11770

    CAS  PubMed  Google Scholar 

  316. Kimura-Kuroda J, Teng X, Komuta Y, Yoshioka N, Sango K, Kawamura K et al (2010) An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury. Mol Cell Neurosci 43:177

    Article  CAS  PubMed  Google Scholar 

  317. Steinhubl SR, Badimon JJ, Bhatt DL, Herbert JM, Luscher TF (2007) Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease. Vasc Med 12:113

    Article  PubMed  Google Scholar 

  318. Knoferle J, Ramljak S, Koch JC, Tonges L, Asif AR, Michel U et al (2010) TGF-beta 1 enhances neurite outgrowth via regulation of proteasome function and EFABP. Neurobiol Dis 38:395

    Article  PubMed  CAS  Google Scholar 

  319. Abe K, Chu PJ, Ishihara A, Saito H (1996) Transforming growth factor-beta 1 promotes re-elongation of injured axons of cultured rat hippocampal neurons. Brain Res 723:206

    Article  CAS  PubMed  Google Scholar 

  320. Lindholm D, Hengerer B, Zafra F, Thoenen H (1990) Transforming growth factor-beta 1 stimulates expression of nerve growth factor in the rat CNS. Neuroreport 1:9

    Article  CAS  PubMed  Google Scholar 

  321. Dobretsov M, Dobretsov A, Kuffler DP (1994) Influence of factors released from sciatic nerve on adult dorsal root ganglion neurons. J Neurobiol 25:1249

    Article  CAS  PubMed  Google Scholar 

  322. Sulaiman OA, Gordon T (2002) Transforming growth factor-beta and forskolin attenuate the adverse effects of long-term Schwann cell denervation on peripheral nerve regeneration in vivo. Glia 37:206

    Article  PubMed  Google Scholar 

  323. Han QJ, Gao NN, Guo Q, Zhang ZN, Yu WH, Pan J et al (2013) IPP5 inhibits neurite growth in primary sensory neurons by maintaining TGF-beta/Smad signaling. J Cell Sci 126:542

    Article  CAS  PubMed  Google Scholar 

  324. Bielecki T, Dohan Ehrenfest DM, Everts PA, Wiczkowski A (2012) The role of leukocytes from L-PRP/L-PRF in wound healing and immune defense: new perspectives. Curr Pharm Biotechnol 13:1153

    Article  CAS  PubMed  Google Scholar 

  325. McCarrel TM, Minas T, Fortier LA (2012) Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy. J Bone Joint Surg Am 94:e143(1–8)

    Article  Google Scholar 

  326. Everts PA, Hoffmann J, Weibrich G, Mahoney CB, Schonberger JP, van Zundert A et al (2006) Differences in platelet growth factor release and leucocyte kinetics during autologous platelet gel formation. Transfus Med 16:363

    Article  CAS  PubMed  Google Scholar 

  327. Jo CH, Roh YH, Kim JE, Shin S, Yoon KS (2013) Optimizing platelet-rich plasma gel formation by varying time and gravitational forces during centrifugation. J Oral Implantol 39:525

    Article  PubMed  Google Scholar 

  328. Pelletier MH, Malhotra A, Brighton T, Walsh WR, Lindeman R (2013) Platelet function and constituents of platelet rich plasma. Int J Sports Med 34:74

    CAS  PubMed  Google Scholar 

  329. Araki J, Jona M, Eto H, Aoi N, Kato H, Suga H et al (2012) Optimized preparation method of platelet-concentrated plasma and noncoagulating platelet-derived factor concentrates: maximization of platelet concentration and removal of fibrinogen. Tissue Eng Part C Methods 18:176

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  330. Soomekh DJ (2010) Using platelet-rich plasma in the foot and ankle. Foot Ankle Spec 3:88

    Article  PubMed  Google Scholar 

  331. Davis VL, Abukabda AB, Radio NM, Witt-Enderby PA, Clafshenkel WP, Cairone JV et al (2012) Platelet-rich preparations to improve healing. Part II: platelet activation and enrichment, leukocyte inclusion, and other selection criteria. J Oral Implantol

  332. Li M, Zhang C, Yuan T, Chen S, Lu R (2011) Assessment study on a set of platelet-rich plasma preparation. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 25:112

    PubMed  Google Scholar 

  333. Li XJ, Ma SX, Liu JH, Sun GX, Ouyang XL (2004) Effects of preparation and quality control of cryopreserved platelets. Zhongguo Shi Yan Xue Ye Xue Za Zhi 12:519

    PubMed  Google Scholar 

  334. Boswell SG, Cole BJ, Sundman EA, Karas V, Fortier LA (2012) Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy 28:429

    Article  PubMed  Google Scholar 

  335. Dadsetan M, Mirzadeh H, Sharifi-Sanjani N, Salehian P (2001) In vitro studies of platelet adhesion on laser-treated polyethylene terephthalate surface. J Biomed Mater Res 54:540

    Article  CAS  PubMed  Google Scholar 

  336. Mazzocca AD, McCarthy MB, Chowaniec DM, Dugdale EM, Hansen D, Cote MP et al (2012) The positive effects of different platelet-rich plasma methods on human muscle, bone, and tendon cells. Am J Sports Med 40:1742

    Article  PubMed  Google Scholar 

  337. Mazzocca AD, McCarthy MB, Chowaniec DM, Cote MP, Romeo AA, Bradley JP et al (2012) Platelet-rich plasma differs according to preparation method and human variability. J Bone Joint Surg Am 94:308

    Article  PubMed  Google Scholar 

  338. Kaux JF, Le Goff C, Renouf J, Peters P, Lutteri L, Gothot A et al (2011) Comparison of the platelet concentrations obtained in platelet-rich plasma (PRP) between the GPS II and GPS III systems. Pathol Biol (Paris) 59:275

    Article  CAS  Google Scholar 

  339. Perez AG, Lichy R, Lana JF, Rodrigues AA, Luzo AC, Belangero WD et al (2013) Prediction and modulation of platelet recovery by discontinuous centrifugation of whole blood for the preparation of pure platelet-rich plasma. Biores Open Access 2:307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  340. Perazzi A, Busetto R, Martinello T, Drigo M, Pasotto D, Cian F et al (2013) Description of a double centrifugation tube method for concentrating canine platelets. BMC Vet Res 9:146

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  341. Amable PR, Carias RB, Teixeira MV, da Cruz Pacheco I, Correa do Amaral RJ, Granjeiro JM et al (2013) Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther 4:67

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  342. DeLong JM, Russell RP, Mazzocca AD (2012) Platelet-rich plasma: the PAW classification system. Arthroscopy 28:998

    Article  PubMed  Google Scholar 

  343. Kawazoe T, Kim HH (2012) Tissue augmentation by white blood cell-containing platelet-rich plasma. Cell Transplant 21:601

    Article  PubMed  Google Scholar 

  344. Arnoczky SP, Shebani-Rad S (2013) The basic science of platelet-rich plasma (PRP): what clinicians need to know. Sports Med Arthrosc 21:180

    Article  PubMed  Google Scholar 

  345. Rodrigues SV, Acharya AB, Thakur SL (2011) An evaluation of platelet-rich plasma without thrombin activation with or without anorganic bone mineral in the treatment of human periodontal intrabony defects. Platelets 22:353

    Article  CAS  PubMed  Google Scholar 

  346. Cruz O, Kuffler DP (2005) Neuroprotection of adult rat dorsal root ganglion neurons by combined hypothermia and alkalinization against prolonged ischemia. Neuroscience 132:115

    Article  CAS  PubMed  Google Scholar 

  347. Lorbach O, Tompkins M (2012) Rotator cuff: biology and current arthroscopic techniques. Knee Surg Sports Traumatol Arthrosc 20:1003

    Article  PubMed  Google Scholar 

  348. Filardo G, Kon E (2012) PRP: more words than facts. Knee Surg Sports Traumatol Arthrosc 20:1655

    Article  PubMed  Google Scholar 

  349. Al-Majed AA, Neumann CM, Brushart TM, Gordon T (2000) Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J Neurosci 20:2602

    CAS  PubMed  Google Scholar 

  350. Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E et al (2012) Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg 94:298

    Article  PubMed  Google Scholar 

  351. Sanchez M, Anitua E, Orive G, Mujika I, Andia I (2009) Platelet-rich therapies in the treatment of orthopaedic sport injuries. Sports Med 39:345

    Article  PubMed  Google Scholar 

  352. Rabago D, Best TM, Zgierska AE, Zeisig E, Ryan M, Crane D (2009) A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma. Br J Sports Med 43:471

    Article  CAS  PubMed  Google Scholar 

  353. Smith SE, Roukis TS (2009) Bone and wound healing augmentation with platelet-rich plasma. Clin Podiatr Med Surg 26:559

    Article  PubMed  Google Scholar 

  354. Yuan T, Guo SC, Han P, Zhang CQ, Zeng BF (2012) Applications of leukocyte- and platelet-rich plasma (L-PRP) in trauma surgery. Curr Pharm Biotechnol 13:1173

    Article  CAS  PubMed  Google Scholar 

  355. Hildebrandt J (2001) Relevance of nerve blocks in treating and diagnosing low back pain—is the quality decisive? Schmerz 15:474

    Article  CAS  PubMed  Google Scholar 

  356. Sanchez M, Anitua E, Lopez-Vidriero E, Andia I (2010) The future: optimizing the healing environment in anterior cruciate ligament reconstruction. Sports Med Arthrosc 18:48

    Article  PubMed  Google Scholar 

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Correspondence to Damien P. Kuffler.

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Kuffler, D.P. Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction. Mol Neurobiol 52, 990–1014 (2015). https://doi.org/10.1007/s12035-015-9251-x

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