Skip to main content

Advertisement

SpringerLink
Log in

Updates in biological therapies for knee injuries: anterior cruciate ligament

  • Knee: Stem Cells (M Ferretti, Section Editor)
  • Published:
Current Reviews in Musculoskeletal Medicine Aims and scope Submit manuscript

Abstract

There have been many advances in anterior cruciate ligament reconstruction (ACLR) techniques incorporating biological treatment. The aim of this review is to discuss the recent contributions that may enlighten our understanding of biological therapies for anterior cruciate ligament (ACL) injuries and improve management decisions involving these enhancement options. Three main biological procedures will be analyzed: bio-enhanced ACL repair, bio-enhanced ACLR scrutinized under the four basic principles of tissue engineering (scaffolds, cell sources, growth factors/cytokines including platelet-rich plasma, and mechanical stimuli), and remnant-preserving ACLR. There is controversial information regarding remnant-preserving ACLR, since different procedures are grouped under the same designation. A new definition for remnant-preserving ACLR surgery is proposed, dividing it into its three major procedures (selective bundle augmentation, augmentation, and nonfunctional remnant preservation); also, an ACL lesion pattern classification and a treatment algorithm, which will hopefully standardize these terms and procedures for future studies, are presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ajuied A, Wong F, Smith C, Norris M, Earnshaw P, Back D, et al. Anterior cruciate ligament injury and radiologic progression of knee osteoarthritis: a systematic review and meta-analysis. Am J Sports Med. 2013. doi:10.1177/0363546513508376.

    PubMed  Google Scholar 

  2. Chalmers PN, Mall NA, Moric M, Sherman SL, Paletta GP, Cole BJ, et al. Does ACL reconstruction alter natural history?: a systematic literature review of long-term outcomes. J Bone Joint Surg Am. 2014;96(4):292–300. doi:10.2106/JBJS.L.01713.

    Article  PubMed  Google Scholar 

  3. Franciozi CE, Tarini VA, Reginato RD, Goncalves PR, Medeiros VP, Ferretti M, et al. Gradual strenuous running regimen predisposes to osteoarthritis due to cartilage cell death and altered levels of glycosaminoglycans. Osteoarthr Cartil / Osteoarthr Res Soc. 2013;21(7):965–72. doi:10.1016/j.joca.2013.04.007.

    Article  CAS  Google Scholar 

  4. Ferretti M, Levicoff EA, Macpherson TA, Moreland MS, Cohen M, Fu FH. The fetal anterior cruciate ligament: an anatomic and histologic study. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2007;23(3):278–83. doi:10.1016/j.arthro.2006.11.006.

    Article  Google Scholar 

  5. Middleton KK, Hamilton T, Irrgang JJ, Karlsson J, Harner CD, Fu FH. Anatomic anterior cruciate ligament (ACL) reconstruction: a global perspective. Part 1. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2014. doi:10.1007/s00167-014-2846-3.

    Google Scholar 

  6. Leong NL, Petrigliano FA, McAllister DR. Current tissue engineering strategies in anterior cruciate ligament reconstruction. J Biomed Mater Res A. 2013. doi:10.1002/jbm.a.34820.

    Google Scholar 

  7. Anitua E, Sanchez M, Orive G, Andia I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials. 2007;28(31):4551–60. doi:10.1016/j.biomaterials.2007.06.037.

    Article  CAS  PubMed  Google Scholar 

  8. Butler DL, Dyment NA, Shearn JT, Kinneberg KR, Breidenbach AP, Lalley AL, et al. Evolving strategies in mechanobiology to more effectively treat damaged musculoskeletal tissues. J Biomech Eng. 2013;135(2):020301. doi:10.1115/1.4023479.

    Article  PubMed  Google Scholar 

  9. Hsu SL, Liang R, Woo SL. Functional tissue engineering of ligament healing. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:12. doi:10.1186/1758-2555-2-12.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Murray MM, Fleming BC. Biology of anterior cruciate ligament injury and repair: Kappa delta ann doner vaughn award paper 2013. J Orthop Res Off Publ Orthop Res Soc. 2013;31(10):1501–6. doi:10.1002/jor.22420.

    Google Scholar 

  11. Murray MM, Martin SD, Martin TL, Spector M. Histological changes in the human anterior cruciate ligament after rupture. J Bone Joint Surg Am. 2000;82-A(10):1387–97.

    CAS  PubMed  Google Scholar 

  12. Murray E, McKenna EO, Burch LR, Dillon J, Langridge-Smith P, Kolch W, et al. Microarray-formatted clinical biomarker assay development using peptide aptamers to anterior gradient-2. Biochemistry. 2007;46(48):13742–51. doi:10.1021/bi7008739.

    Article  CAS  PubMed  Google Scholar 

  13. Murray MM, Fleming BC. Use of a bioactive scaffold to stimulate anterior cruciate ligament healing also minimizes posttraumatic osteoarthritis after surgery. Am J Sports Med. 2013;41(8):1762–70. doi:10.1177/0363546513483446.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Robayo LM, Moulin VJ, Tremblay P, Cloutier R, Lamontagne J, Larkin AM, et al. New ligament healing model based on tissue-engineered collagen scaffolds. Wound Repair Regen Off Publ Wound Healing Society Eur Tissue Repair Soc. 2011;19(1):38–48. doi:10.1111/j.1524-475X.2010.00640.x.

    Google Scholar 

  15. Vavken P, Fleming BC, Mastrangelo AN, Machan JT, Murray MM. Biomechanical outcomes after bioenhanced anterior cruciate ligament repair and anterior cruciate ligament reconstruction are equal in a porcine model. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2012;28(5):672–80. doi:10.1016/j.arthro.2011.10.008.

    Article  Google Scholar 

  16. Fisher MB, Liang R, Jung HJ, Kim KE, Zamarra G, Almarza AJ, et al. Potential of healing a transected anterior cruciate ligament with genetically modified extracellular matrix bioscaffolds in a goat model. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2012;20(7):1357–65. doi:10.1007/s00167-011-1800-x.

    Article  Google Scholar 

  17. Magarian EM, Fleming BC, Harrison SL, Mastrangelo AN, Badger GJ, Murray MM. Delay of 2 or 6 weeks adversely affects the functional outcome of augmented primary repair of the porcine anterior cruciate ligament. Am J Sports Med. 2010;38(12):2528–34. doi:10.1177/0363546510377416.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Mastrangelo AN, Haus BM, Vavken P, Palmer MP, Machan JT, Murray MM. Immature animals have higher cellular density in the healing anterior cruciate ligament than adolescent or adult animals. J Orthop Res Off Publ Orthop Res Soc. 2010;28(8):1100–6. doi:10.1002/jor.21070.

    Google Scholar 

  19. Steinert AF, Kunz M, Prager P, Barthel T, Jakob F, Noth U, et al. Mesenchymal stem cell characteristics of human anterior cruciate ligament outgrowth cells. Tissue Eng A. 2011;17(9–10):1375–88. doi:10.1089/ten.TEA.2010.0413.

    Article  CAS  Google Scholar 

  20. Shao HJ, Chen CS, Lee YT, Wang JH, Young TH. The phenotypic responses of human anterior cruciate ligament cells cultured on poly(epsilon-caprolactone) and chitosan. J Biomed Mater Res A. 2010;93(4):1297–305. doi:10.1002/jbm.a.32629.

    PubMed  Google Scholar 

  21. James R, Toti US, Laurencin CT, Kumbar SG. Electrospun nanofibrous scaffolds for engineering soft connective tissues. Methods Mol Biol. 2011;726:243–58. doi:10.1007/978-1-61779-052-2_16. This article deliberated about the electrospinning technique as a reliable and promising option to fabricate nanofiber matrices nanostructured to mimic the collagen fiber dimensions in extracellular matrix as a potential tissue-engineered scaffold, given its improved biological performance over more bulk materials in aspects of cellular infiltration and in vivo integration.

    Article  CAS  PubMed  Google Scholar 

  22. Peach MS, Kumbar SG, James R, Toti US, Balasubramaniam D, Deng M, et al. Design and optimization of polyphosphazene functionalized fiber matrices for soft tissue regeneration. J Biomed Nanotechnol. 2012;8(1):107–24.

    Article  CAS  PubMed  Google Scholar 

  23. Chung AS, Hwang HS, Das D, Zuk P, McAllister DR, Wu BM. Lamellar stack formation and degradative behaviors of hydrolytically degraded poly(epsilon-caprolactone) and poly(glycolide-epsilon-caprolactone) blended fibers. J Biomed Mater Res B Appl Biomater. 2012;100(1):274–84. doi:10.1002/jbm.b.31950.

    Article  PubMed  Google Scholar 

  24. Laurent CP, Durville D, Mainard D, Ganghoffer JF, Rahouadj R. A multilayer braided scaffold for Anterior Cruciate Ligament: mechanical modeling at the fiber scale. J Mech Behav Biomed Mater. 2012;12:184–96. doi:10.1016/j.jmbbm.2012.03.005.

    Article  CAS  PubMed  Google Scholar 

  25. Hansson A, Hashom N, Falson F, Rousselle P, Jordan O, Borchard G. In vitro evaluation of an RGD-functionalized chitosan derivative for enhanced cell adhesion. Carbohydr Polym. 2012;90(4):1494–500. doi:10.1016/j.carbpol.2012.07.020.

    Article  CAS  PubMed  Google Scholar 

  26. Erisken C, Zhang X, Moffat KL, Levine WN, Lu HH. Scaffold fiber diameter regulates human tendon fibroblast growth and differentiation. Tissue Eng A. 2013;19(3–4):519–28. doi:10.1089/ten.tea.2012.0072. This article demonstrated that scaffold fiber diameter modulates the response of human tendon fibroblasts and can be used as a driving parameter in soft tissue healing response.

    Article  CAS  Google Scholar 

  27. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7. doi:10.1080/14653240600855905.

    Article  CAS  PubMed  Google Scholar 

  28. Eagan MJ, Zuk PA, Zhao KW, Bluth BE, Brinkmann EJ, Wu BM, et al. The suitability of human adipose-derived stem cells for the engineering of ligament tissue. J Tissue Eng Regen Med. 2011. doi:10.1002/term.474.

    PubMed  Google Scholar 

  29. Matsumoto T, Kubo S, Sasaki K, Kawakami Y, Oka S, Sasaki H, et al. Acceleration of tendon-bone healing of anterior cruciate ligament graft using autologous ruptured tissue. Am J Sports Med. 2012;40(6):1296–302. doi:10.1177/0363546512439026.

    Article  PubMed  Google Scholar 

  30. Mifune Y, Matsumoto T, Ota S, Nishimori M, Usas A, Kopf S, et al. Therapeutic potential of anterior cruciate ligament-derived stem cells for anterior cruciate ligament reconstruction. Cell Transplant. 2012;21(8):1651–65. doi:10.3727/096368912X647234.

    Article  PubMed  Google Scholar 

  31. Mifune Y, Matsumoto T, Takayama K, Terada S, Sekiya N, Kuroda R, et al. Tendon graft revitalization using adult anterior cruciate ligament (ACL)-derived CD34+ cell sheets for ACL reconstruction. Biomaterials. 2013;34(22):5476–87. doi:10.1016/j.biomaterials.2013.04.013.

    Article  CAS  PubMed  Google Scholar 

  32. Canseco JA, Kojima K, Penvose AR, Ross JD, Obokata H, Gomoll AH, et al. Effect on ligament marker expression by direct-contact co-culture of mesenchymal stem cells and anterior cruciate ligament cells. Tissue Eng A. 2012;18(23–24):2549–58. doi:10.1089/ten.TEA.2012.0030. This study demonstrated a better ligament marker expression using a 50% co-culture of ACL cells and MSCs, instead of either cell population alone presenting as a potential cell-source option for ACL-enhanced healing therapies.

    Article  CAS  Google Scholar 

  33. Deehan DJ, Dowen DJ, Sprowson A, Ferguson L, Prathalingham N, Isaacs J, et al. Differential release of heterogeneous human mesenchymal stem cell populations from haemarthrotic traumatic knee injury. Am J Stem Cell Res. 2012;1:1–8.

    Google Scholar 

  34. Knuth CA, Clark ME, Meeson AP, Khan SK, Dowen DJ, Deehan DJ, et al. Low oxygen tension is critical for the culture of human mesenchymal stem cells with strong osteogenic potential from haemarthrosis fluid. Stem Cell Rev. 2013;9(5):599–608. doi:10.1007/s12015-013-9446-3.

    Article  CAS  PubMed  Google Scholar 

  35. Rogers CM, Deehan DJ, Knuth CA, Rose FR, Shakesheff KM, Oldershaw RA. Biocompatibility and enhanced osteogenic differentiation of human mesenchymal stem cells in response to surface engineered poly(d, l-lactic-co-glycolic acid) microparticles. J Biomed Mater Res A. 2013. doi:10.1002/jbm.a.35063.

    PubMed  Google Scholar 

  36. Sun L, Hou C, Wu B, Tian M, Zhou X. Effect of muscle preserved on tendon graft on intra-articular healing in anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2013;21(8):1862–8. doi:10.1007/s00167-012-2181-5.

    Article  Google Scholar 

  37. Muller B, Bowman Jr KF, Bedi A. ACL graft healing and biologics. Clin Sports Med. 2013;32(1):93–109. doi:10.1016/j.csm.2012.08.010.

    Article  PubMed  Google Scholar 

  38. Wang Y, Tang Z, Xue R, Singh GK, Lv Y, Shi K, et al. TGF-beta1 promoted MMP-2 mediated wound healing of anterior cruciate ligament fibroblasts through NF-kappaB. Connect Tissue Res. 2011;52(3):218–25. doi:10.3109/03008207.2010.516849.

    Article  CAS  PubMed  Google Scholar 

  39. Wang CJ, Weng LH, Hsu SL, Sun YC, Yang YJ, Chan YS, et al. pCMV-BMP-2-transfected cell-mediated gene therapy in anterior cruciate ligament reconstruction in rabbits. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2010;26(7):968–76. doi:10.1016/j.arthro.2009.11.014.

    Article  CAS  Google Scholar 

  40. Magnussen RA, Flanigan DC, Pedroza AD, Heinlein KA, Kaeding CC. Platelet rich plasma use in allograft ACL reconstructions: two-year clinical results of a MOON cohort study. Knee. 2013;20(4):277–80. doi:10.1016/j.knee.2012.12.001.

    Article  PubMed  Google Scholar 

  41. Mirzatolooei F, Alamdari MT, Khalkhali HR. The impact of platelet-rich plasma on the prevention of tunnel widening in anterior cruciate ligament reconstruction using quadrupled autologous hamstring tendon: a randomised clinical trial. Bone Joint J. 2013;95-B(1):65–9. doi:10.1302/0301-620X.95B1.30487.

    Article  CAS  PubMed  Google Scholar 

  42. Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev. 2013;12, CD010071. doi:10.1002/14651858.CD010071.pub2. This judicious systematic review concluded that there is currently insufficient evidence to support the use of PRP for treating musculoskeletal soft tissue injuries, including ACL lesions.

    PubMed  Google Scholar 

  43. Cervellin M, de Girolamo L, Bait C, Denti M, Volpi P. Autologous platelet-rich plasma gel to reduce donor-site morbidity after patellar tendon graft harvesting for anterior cruciate ligament reconstruction: a randomized, controlled clinical study. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2012;20(1):114–20. doi:10.1007/s00167-011-1570-5.

    Article  CAS  Google Scholar 

  44. de Almeida AM, Demange MK, Sobrado MF, Rodrigues MB, Pedrinelli A, Hernandez AJ. Patellar tendon healing with platelet-rich plasma: a prospective randomized controlled trial. Am J Sports Med. 2012;40(6):1282–8. doi:10.1177/0363546512441344.

    Article  PubMed  Google Scholar 

  45. Debandi A, Maeyama A, Hoshino Y, Asai S, Goto B, Smolinski P, et al. The effect of tunnel placement on rotational stability after ACL reconstruction: evaluation with use of triaxial accelerometry in a porcine model. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2013;21(3):589–95. doi:10.1007/s00167-012-1961-2.

    Article  Google Scholar 

  46. Ekdahl M, Nozaki M, Ferretti M, Tsai A, Smolinski P, Fu FH. The effect of tunnel placement on bone-tendon healing in anterior cruciate ligament reconstruction in a goat model. Am J Sports Med. 2009;37(8):1522–30. doi:10.1177/0363546509332503.

    Article  PubMed  Google Scholar 

  47. Kondo E, Merican AM, Yasuda K, Amis AA. Biomechanical comparison of anatomic double-bundle, anatomic single-bundle, and nonanatomic single-bundle anterior cruciate ligament reconstructions. Am J Sports Med. 2011;39(2):279–88. doi:10.1177/0363546510392350.

    Article  PubMed  Google Scholar 

  48. Lim HC, Yoon YC, Wang JH, Bae JH. Anatomical versus non-anatomical single bundle anterior cruciate ligament reconstruction: a cadaveric study of comparison of knee stability. Clin Orthop Surg. 2012;4(4):249–55. doi:10.4055/cios.2012.4.4.249.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Okafor EC, Utturkar GM, Widmyer MR, Abebe ES, Collins AT, Taylor DC, et al. The effects of femoral graft placement on cartilage thickness after anterior cruciate ligament reconstruction. J Biomech. 2014;47(1):96–101. doi:10.1016/j.jbiomech.2013.10.003.

    Article  PubMed  Google Scholar 

  50. Subramony SD, Su A, Yeager K, Lu HH. Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds. J Biomech. 2013. doi:10.1016/j.jbiomech.2013.10.016. This experimental study aligned all the four tissue-engineering basic principles (biomaterial scaffold, cell source, growth factor, and mechanical stimulation) to analyze optimal strategies for MSCs differentiation in a potential nanofiber ligament scaffold.

    PubMed  Google Scholar 

  51. Abat F, Gelber PE, Erquicia JI, Pelfort X, Tey M, Monllau JC. Promising short-term results following selective bundle reconstruction in partial anterior cruciate ligament tears. Knee. 2013;20(5):332–8. doi:10.1016/j.knee.2013.05.006.

    Article  PubMed  Google Scholar 

  52. Borbon CA, Mouzopoulos G, Siebold R. Why perform an ACL augmentation? Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2012;20(2):245–51. doi:10.1007/s00167-011-1565-2.

    Article  Google Scholar 

  53. Buda R, Ruffilli A, Parma A, Pagliazzi G, Luciani D, Ramponi L, et al. Partial ACL tears: anatomic reconstruction versus nonanatomic augmentation surgery. Orthopedics. 2013;36(9):e1108–13. doi:10.3928/01477447-20130821-10.

    PubMed  Google Scholar 

  54. Colombet P, Dejour D, Panisset JC, Siebold R, French Arthroscopy S. Current concept of partial anterior cruciate ligament ruptures. Orthop Traumatol Surg Res. 2010;96(8 Suppl):S109–18. doi:10.1016/j.otsr.2010.09.003.

    Article  CAS  PubMed  Google Scholar 

  55. Crain EH, Fithian DC, Paxton EW, Luetzow WF. Variation in anterior cruciate ligament scar pattern: does the scar pattern affect anterior laxity in anterior cruciate ligament-deficient knees? Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2005;21(1):19–24. doi:10.1016/j.arthro.2004.09.015.

    Article  Google Scholar 

  56. Dejour D, Ntagiopoulos PG, Saggin PR, Panisset JC. The diagnostic value of clinical tests, magnetic resonance imaging, and instrumented laxity in the differentiation of complete versus partial anterior cruciate ligament tears. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2013;29(3):491–9. doi:10.1016/j.arthro.2012.10.013.

    Article  Google Scholar 

  57. Demirag B, Ermutlu C, Aydemir F, Durak K. A comparison of clinical outcome of augmentation and standard reconstruction techniques for partial anterior cruciate ligament tears. Eklem hastaliklari ve cerrahisi = Jt Dis Relat Surg. 2012;23(3):140–4. Randomized clinical trial. Remnant-preserving ACLR (type: augmentation) proved to be as effective as the standard technique; however, it led to less tunnel enlargement, particularly at the tibia.

    Google Scholar 

  58. Gohil S, Annear PO, Breidahl W. Anterior cruciate ligament reconstruction using autologous double hamstrings: a comparison of standard versus minimal debridement techniques using MRI to assess revascularisation. A randomised prospective study with a one-year follow-up. J Bone Joint Surg (Br). 2007;89(9):1165–71. doi:10.1302/0301-620x.89b9.19339.

    Article  CAS  Google Scholar 

  59. Hong L, Li X, Zhang H, Liu X, Zhang J, Shen JW, et al. Anterior cruciate ligament reconstruction with remnant preservation: a prospective, randomized controlled study. Am J Sports Med. 2012;40(12):2747–55. doi:10.1177/0363546512461481. Randomized clinical trial. remnant-preserving aclr (type: nonfunctional remnant preservation) proved to be as effective as the standard technique regarding stability, synovial coverage, and proprioception recovery.

    Article  PubMed  Google Scholar 

  60. Kazusa H, Nakamae A, Ochi M. Augmentation technique for anterior cruciate ligament injury. Clin Sports Med. 2013;32(1):127–40. doi:10.1016/j.csm.2012.08.012.

    Article  PubMed  Google Scholar 

  61. Muneta T, Koga H, Ju YJ, Horie M, Nakamura T, Sekiya I. Remnant volume of anterior cruciate ligament correlates preoperative patients’ status and postoperative outcome. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2013;21(4):906–13. doi:10.1007/s00167-012-2023-5.

    Article  Google Scholar 

  62. Pujol N, Colombet P, Potel JF, Cucurulo T, Graveleau N, Hulet C, et al. Anterior cruciate ligament reconstruction in partial tear: selective anteromedial bundle reconstruction conserving the posterolateral remnant versus single-bundle anatomic ACL reconstruction: preliminary 1-year results of a prospective randomized study. Orthop Traumatol Surg Res. 2012;98(8 Suppl):S171–7. doi:10.1016/j.otsr.2012.09.007. Randomized clinical trial. Remnant-preserving ACLR (type: selective bundle augmentation reconstructing the anteromedial bundle) proved to be as effective as the standard technique regarding clinical results; however, it showed better control of anterior laxity.

    Article  CAS  PubMed  Google Scholar 

  63. Zhang Q, Zhang S, Cao X, Liu L, Liu Y, Li R. The effect of remnant preservation on tibial tunnel enlargement in ACL reconstruction with hamstring autograft: a prospective randomized controlled trial. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2014;22(1):166–73. doi:10.1007/s00167-012-2341-7. Randomized clinical trial. Remnant-preserving ACLR (type: augmentation) proved to be as effective as the standard technique regarding clinical results; however, it led to less tibial tunnel enlargement.

    Article  Google Scholar 

  64. Dhillon MS, Bali K, Prabhakar S. Differences among mechanoreceptors in healthy and injured anterior cruciate ligaments and their clinical importance. Muscles Ligaments Tendons J. 2012;2(1):38–43.

    PubMed Central  PubMed  Google Scholar 

  65. Dhillon MS, Bali K, Vasistha RK. Immunohistological evaluation of proprioceptive potential of the residual stump of injured anterior cruciate ligaments (ACL). Int Orthop. 2010;34(5):737–41. doi:10.1007/s00264-009-0948-1.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Ochi M, Abouheif MM, Kongcharoensombat W, Nakamae A, Adachi N, Deie M. Double bundle arthroscopic Anterior Cruciate Ligament reconstruction with remnant preserving technique using a hamstring autograft. Sports Med Arthrosc Rehabil Ther Technol. 2011;3:30. doi:10.1186/1758-2555-3-30.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Mifune Y, Ota S, Takayama K, Hoshino Y, Matsumoto T, Kuroda R, et al. Therapeutic advantage in selective ligament augmentation for partial tears of the anterior cruciate ligament: results in an animal model. Am J Sports Med. 2013;41(2):365–73. doi:10.1177/0363546512471614.

    Article  PubMed  Google Scholar 

  68. Lee DH, Ng J, Chung JW, Sonn CH, Lee KM, Han SB. Impact of chronicity of injury on the proportion of mesenchymal stromal cells derived from anterior cruciate ligaments. Cytotherapy. 2014. doi:10.1016/j.jcyt.2013.08.001.

    Google Scholar 

  69. Mitani G, Sato M, Yamato M, Kokubo M, Takagaki T, Ebihara G, et al. Potential utility of cell sheets derived from the anterior cruciate ligament and synovium fabricated in temperature-responsive culture dishes. J Biomed Mater Res A. 2013. doi:10.1002/jbm.a.34962.

    PubMed  Google Scholar 

  70. Nohmi S, Yamamoto Y, Mizukami H, Ishibashi Y, Tsuda E, Maniwa K, et al. Post injury changes in the properties of mesenchymal stem cells derived from human anterior cruciate ligaments. Int Orthop. 2012;36(7):1515–22. doi:10.1007/s00264-012-1484-y.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. Mario Ferretti for his support and contribution to this paper.

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Carlos Eduardo da Silveira Franciozi and Rene Jorge Abdall are consultants to PCE- Smith & Nephew distributor in Brazil.

Sheila Jean McNeill Ingham, Guilherme Conforto Gracitelli, and Marcus Vinicius Malheiros Luzo declare that they have no conflict of interest.

Freddie H. Fu received royalties from Arthrocare, deposited to University of Pittsburgh School of Medicine Accounts (ended 11/2012).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Borges Lagoa, 783-5°Andar, Vila Clementino, 04038-032, São Paulo, SP, Brazil

    Carlos Eduardo da Silveira Franciozi, Sheila Jean McNeill Ingham, Guilherme Conforto Gracitelli, Marcus Vinicius Malheiros Luzo & Rene Jorge Abdalla

  2. Knee Institute, Hospital do Coração, São Paulo, SP, Brazil

    Carlos Eduardo da Silveira Franciozi, Sheila Jean McNeill Ingham & Rene Jorge Abdalla

  3. Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 3471 Fifth Avenue, Suite 1011, Pittsburgh, PA, 15213, USA

    Freddie H. Fu

Authors
  1. Carlos Eduardo da Silveira Franciozi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheila Jean McNeill Ingham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guilherme Conforto Gracitelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcus Vinicius Malheiros Luzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Freddie H. Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rene Jorge Abdalla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlos Eduardo da Silveira Franciozi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silveira Franciozi, C.E., Ingham, S.J.M., Gracitelli, G.C. et al. Updates in biological therapies for knee injuries: anterior cruciate ligament. Curr Rev Musculoskelet Med 7, 228–238 (2014). https://doi.org/10.1007/s12178-014-9228-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12178-014-9228-9

Keywords

Search

Navigation