Why menisci show higher healing rate when repaired during ACL reconstruction? Growth factors release can be the explanation

  • L. de GirolamoEmail author
  • E. Galliera
  • P. Volpi
  • M. Denti
  • G. Dogliotti
  • A. Quaglia
  • P. Cabitza
  • M. M. Corsi Romanelli
  • P. Randelli
Experimental Study



Healing rate of meniscus repair is higher when the suture is associated with anterior cruciate ligament reconstruction. A possible explanation can be a different pattern of release of growth factors between anterior cruciate ligament reconstruction and isolated meniscus surgery. Hypothesis of this study is that the concentrations of bFGF, TGF-β and platelet-derived growth factor (PDGF) in joint fluid, immediately after single-bundle anterior cruciate ligament reconstruction and arthroscopic partial meniscectomy, can be different.


Twenty consecutive patients underwent partial medial meniscectomy and twenty consecutive patients underwent single-bundle anterior cruciate ligament reconstruction with hamstring grafts were enrolled in the study. Thirty minutes after the end of the surgical procedure, a sample of joint fluid, as well of venous blood, was collected from all the patients. Concentrations of growth factors were determined by enzyme-linked immunosorbent assay.


The peripheral blood concentration of TGF-β, bFGF and PDGF was comparable between partial meniscectomy and anterior cruciate ligament reconstruction groups. No differences between the two surgical techniques were also found in term of TGF-β and bFGF joint fluid concentration, whereas joint PDGF concentration of anterior cruciate ligament reconstruction patients was significantly higher than the one found in partial meniscectomy patients.


A significant growth factors release was detected in the knee joint during arthroscopic surgery. PDGF concentration was significantly higher in anterior cruciate ligament reconstructed knee than in the meniscectomy group. PDGF can play an important role enhancing the healing response of meniscus suture and can be one of the biological reasons of the higher meniscal healing rate in anterior cruciate ligament reconstructed knee.


Meniscal repair ACL reconstruction Platelet-derived growth factor Basic fibroblastic growth factor Transforming growth factor-β Tissue healing Tissue remodelling 


Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Allen CR, Wong EK, Livesay GA, Sakane M, Fu FH, Woo SL (2000) Importance of the medial meniscus in the anterior cruciate ligament-deficient knee. J Orthop Res 18:109–115PubMedCrossRefGoogle Scholar
  2. 2.
    Anitua E, Sanchez M, Zalduendo MM, de la Fuente M, Prado R, Orive G, Andía I (2009) Fibroblastic response to treatment with different preparations rich in growth factors. Cell Prolif 42:162–170PubMedCrossRefGoogle Scholar
  3. 3.
    Anz AW, Rodkey WG (2012) Biological enhancement of meniscus repair and replacement. Sports Med Arthrosc 20:115–120PubMedCrossRefGoogle Scholar
  4. 4.
    Arnoczky SP, Warren RF (1982) Microvasculature of the human meniscus. Am J Sports Med 10:90–95Google Scholar
  5. 5.
    Barber FA, Bava ED (2012) Meniscal repair: the newest fixators. Sports Med Arthrosc 20:95–100PubMedCrossRefGoogle Scholar
  6. 6.
    Bhargava MM, Hidaka C, Hannafin JA, Doty S, Warren RF (2005) Effects of hepatocyte growth factor and platelet-derived growth factor on the repair of meniscal defects in vitro. In Vitro Cell Dev Biol Anim 41:305–310PubMedCrossRefGoogle Scholar
  7. 7.
    Collier S, Ghosh P (1995) Effects of transforming growth factor beta on proteoglycan synthesis by cell and explant cultures derived from the knee joint meniscus. Osteoarthritis Cartilage 3:127–138PubMedCrossRefGoogle Scholar
  8. 8.
    Creaney L, Hamilton B (2008) Growth factor delivery methods in the management of sports injuries: the state of play. Br J Sports Med 42:314–320PubMedCrossRefGoogle Scholar
  9. 9.
    Delos D, Rodeo SA (2011) Enhancing meniscal repair through biology: platelet-rich plasma as an alternative strategy. Instr Course Lect 60:453–460PubMedGoogle Scholar
  10. 10.
    Freedman KB, Nho SJ, Cole BJ (2003) Marrow stimulating technique to augment meniscus repair. Arthroscopy 19:794–798PubMedCrossRefGoogle Scholar
  11. 11.
    Galliera E, de Girolamo L, Randelli P, Volpi P, Dogliotti G, Quaglia A, Banfi G, Cabitza P, Corsi MM, Denti M (2011) High articular levels of the angiogenetic factors VEGF (Vascular Endothelial Growth Factor) and VEGF-Receptor 2 as tissue healing biomarkers after single bundle anterior cruciate ligament reconstruction. J Biol Regul Homeost Agents 25:85–91PubMedGoogle Scholar
  12. 12.
    Hayward AL, Deehan DJ, Aspden RM, Sutherland AG (2011) Analysis of sequential cytokine release after ACL reconstruction. Knee Surg Sports Traumatol Arthrosc 19:1709–1715PubMedCrossRefGoogle Scholar
  13. 13.
    Henning CE, Lynch MA, Yearout KM, Vequist SW, Stallbaumer RJ, Decker KA (1990) Arthroscopic meniscal repair using an exogenous fibrin clot. Clin Orthop Relat Res 252:64–72Google Scholar
  14. 14.
    Henning CE, Yearout KM, Vequist SW, Stallbaumer RJ, Decker KA (1991) Use of the fascia sheath coverage and exogenous fibrin clot in the treatment of complex meniscal tears. Am J Sports Med 19:626–631PubMedCrossRefGoogle Scholar
  15. 15.
    Huey DJ, Athanasiou KA (2011) Maturational growth of self-assembled, functional menisci as a result of TGF-β1 and enzymatic chondroitinase-ABC stimulation. Biomaterials 32:2052–2058PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Kasemkijwattana C, Menetrey J, Goto H, Niyibizi C, Fu FH, Huard J (2000) The use of growth factors, gene therapy and tissue engineering to improve meniscal healing. Mater Sci Eng C Mater Biol Appl 13:19–28CrossRefGoogle Scholar
  17. 17.
    Liu C, Toma IC, Mastrogiacomo M, Krettek C, von Lewinski G, Jagodzinski M (2013) Meniscus reconstruction: today’s achievements and premises for the future. Arch Orthop Trauma Surg 133:95–109PubMedCrossRefGoogle Scholar
  18. 18.
    Lohmander LS, Englund PM, Dahl LL, Roos EM (2007) The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med 35:1756–1769PubMedCrossRefGoogle Scholar
  19. 19.
    Makris EA, Hadidi P, Athanasiou KA (2011) The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials 32:7411–7431PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Meister K, Indelicato PA, Spanier S, Franklin J, Batts J (2004) Histology of the torn meniscus: a comparison of histologic differences in meniscal tissue between tears in anterior cruciate ligament-intact and anterior cruciate ligament-deficient knees. Am J Sports Med 32:1479–1483PubMedCrossRefGoogle Scholar
  21. 21.
    Musahl V, Citak M, O’Loughlin PF, Choi D, Bedi A, Pearle AD (2010) The effect of medial versus lateral meniscectomy on the stability of the anterior cruciate ligament-deficient knee. Am J Sports Med 38:1591–1597PubMedCrossRefGoogle Scholar
  22. 22.
    Mustoe TA, Pierce GF, Morishima C, Deuel TF (1991) Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. J Clin Invest 87:694–703PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Noyes FR, Barber-Westin SD (2012) Treatment of meniscus tears during anterior cruciate ligament reconstruction. Arthroscopy 28:123–130PubMedCrossRefGoogle Scholar
  24. 24.
    Pangborn CA, Athanasiou KA (2005) Effects of growth factors on meniscal fibrochondrocytes. Tissue Eng 11:1141–1148PubMedCrossRefGoogle Scholar
  25. 25.
    Paxton ES, Stock MV, Brophy RH (2011) Meniscal repair versus partial meniscectomy: a systematic review comparing reoperation rates and clinical outcomes. Arthroscopy 27:1275–1288PubMedCrossRefGoogle Scholar
  26. 26.
    Popescu D, Sastre S, Garcia AI, Tomas X, Reategui D, Caballero M (2013) MR-arthrography assessment after repair of chronic meniscal tears. Knee Surg Sports Traumatol Arthrosc. (Epub ahead of print)Google Scholar
  27. 27.
    Rangger C, Klestil T, Gloetzer W, Kemmler G, Benedetto KP (1995) Osteoarthritis after arthroscopic partial meniscectomy. Am J Sports Med 23:240–244PubMedCrossRefGoogle Scholar
  28. 28.
    Rhee S, Grinnell F (2006) P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human fibroblasts. J Cell Biol 172:423–432PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Robson MC, Phillips LG, Thomason A, Robson LE, Pierce GF (1992) Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet 339:23–25PubMedCrossRefGoogle Scholar
  30. 30.
    Ronnstrand L, Heldin CH (2001) Mechanisms of platelet-derived growth factor-induced chemotaxis. Int J Cancer 91:757–762PubMedCrossRefGoogle Scholar
  31. 31.
    Roos EM, Ostenberg A, Roos H, Ekdahl C, Lohmander LS (2001) Long-term outcome of meniscectomy: symptoms, function, and performance tests in patients with or without radiographic osteoarthritis compared to matched controls. Osteoarthritis Cartilage 9:316–324PubMedCrossRefGoogle Scholar
  32. 32.
    Sanchez M, Anitua E, Cugat R, Azofra J, Guadilla J, Seijas R, Andia I (2009) Nonunions treated with autologous preparation rich in growth factors. J Orthop Trauma 23:52–59PubMedCrossRefGoogle Scholar
  33. 33.
    Scordino LE, Deberardino TM (2012) Biologic enhancement of meniscus repair. Clin Sports Med 31:91–100PubMedCrossRefGoogle Scholar
  34. 34.
    Shelbourne KD, Carr DR (2003) Meniscal repair compared with meniscectomy for bucket-handle medial meniscal tears in anterior cruciate ligament-reconstructed knees. Am J Sports Med 31:718–723PubMedGoogle Scholar
  35. 35.
    Shelbourne KD, Gray T (2009) Minimum 10-year results after anterior cruciate ligament reconstruction: how the loss of normal knee motion compounds other factors related to the development of osteoarthritis after surgery. Am J Sports Med 37:471–480PubMedCrossRefGoogle Scholar
  36. 36.
    Smith JP 3rd, Barrett GR (2001) Medial and lateral meniscal tear patterns in anterior cruciate ligament-deficient knees. A prospective analysis of 575 tears. Am J Sports Med 29:415–419PubMedGoogle Scholar
  37. 37.
    Stärke C, Kopf S, Petersen W, Becker R (2009) Meniscal repair. Arthroscopy 25:1033–1044PubMedCrossRefGoogle Scholar
  38. 38.
    Stewart K, Pabbruwe M, Dickinson S, Sims T, Hollander AP, Chaudhuri JB (2007) The effect of growth factor treatment on meniscal chondrocyte proliferation and differentiation on polyglycolic acid scaffolds. Tissue Eng 13:271–280PubMedCrossRefGoogle Scholar
  39. 39.
    Tachibana Y, Sakaguchi K, Goto T, Oda H, Yamazaki K, Iida S (2010) Repair integrity evaluated by second-look arthroscopy after arthroscopic meniscal repair with the FasT-Fix during anterior cruciate ligament reconstruction. Am J Sports Med 38:965–971PubMedCrossRefGoogle Scholar
  40. 40.
    Tandogan RN, Taşer O, Kayaalp A, Taşkiran E, Pinar H, Alparslan B, Alturfan A (2004) Analysis of meniscal and chondral lesions accompanying anterior cruciate ligament tears: relationship with age, time from injury, and level of sport. Knee Surg Sports Traumatol Arthrosc 12:262–270PubMedCrossRefGoogle Scholar
  41. 41.
    Taylor SA, Rodeo SA (2013) Augmentation techniques for isolated meniscal tears. Curr Rev Musculoskelet Med 6:95–101PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Toman CV, Dunn WR, Spindler KP, Amendola A, Andrish JT, Bergfeld JA, Flanigan D, Jones MH, Kaeding CC, Marx RG, Matava MJ, McCarty EC, Parker RD, Wolcott M, Vidal A, Wolf BR, Huston LJ, Harrell FE Jr, Wright RW (2009) Success of meniscal repair at anterior cruciate ligament reconstruction. Am J Sports Med 37:1111–1115PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    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 19:1675–1682PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Wasserstein D, Dwyer T, Gandhi R, Austin PC, Mahomed N, Ogilvie-Harris D (2013) A matched-cohort population study of reoperation after meniscal repair with and without concomitant anterior cruciate ligament reconstruction. Am J Sports Med 41:349–355PubMedCrossRefGoogle Scholar
  45. 45.
    Wieman TJ, Smiell JM, Su Y (1998) Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care 21:822–827PubMedCrossRefGoogle Scholar
  46. 46.
    Wu L, Brucker M, Gruskin E, Roth SI, Mustoe TA (1997) Differential effects of platelet-derived growth factor BB in accelerating wound healing in aged versus young animals: the impact of tissue hypoxia. Plast Reconstr Surg 99:815–822PubMedCrossRefGoogle Scholar
  47. 47.
    Wu WH, Hackett T, Richmond JC (2002) Effects of meniscal and articular surface status on knee stability, function, and symptoms after anterior cruciate ligament reconstruction: a long-term prospective study. Am J Sports Med 30:845–850PubMedGoogle Scholar
  48. 48.
    Zaleskas JM, Kinner B, Freyman TM, Yannas IV, Gibson LJ, Spector M (2001) Growth factor regulation of smooth muscle actin expression and contraction of human articular chondrocytes and meniscal cells in a collagen GAG matrix. Exp Cell Res 270:21–31PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • L. de Girolamo
    • 1
    Email author
  • E. Galliera
    • 1
    • 2
  • P. Volpi
    • 3
  • M. Denti
    • 3
  • G. Dogliotti
    • 4
  • A. Quaglia
    • 3
  • P. Cabitza
    • 4
    • 5
  • M. M. Corsi Romanelli
    • 4
    • 5
  • P. Randelli
    • 4
    • 5
  1. 1.IRCCS Istituto Ortopedico GaleazziMilanItaly
  2. 2.Dipartimento di Scienze Biomediche, Chirurgiche ed OdontoiatricheUniversità degli Studi di MilanoMilanItaly
  3. 3.Istituto Clinico Humanitas IRCCSRozzanoItaly
  4. 4.Dipartimento di Scienze Biomediche per la SaluteUniversità degli Studi di MilanoMilanItaly
  5. 5.IRCCS Policlinico San DonatoSan Donato MilaneseItaly

Personalised recommendations