Current Reviews in Musculoskeletal Medicine

, Volume 7, Issue 3, pp 247–255 | Cite as

Updates in biological therapies for knee injuries: menisci

  • Camila Cohen KalekaEmail author
  • Pedro Debieux
  • Diego da Costa Astur
  • Gustavo Gonçalves Arliani
  • Moisés Cohen
Knee: Stem Cells (M Ferretti, Section Editor)


The preservation of meniscal tissue is paramount for long-term joint function, especially in younger patients who are athletically active. Many studies have reported encouraging results following the repair of meniscus tears, including both simple longitudinal tears located in the periphery and complex multiplanar tears that extend into the central third avascular region. However, most types of meniscal lesions are managed with a partial meniscectomy. Options to restore the meniscus range from an allograft transplantation to the use of synthetic and biological technologies. Recent studies have demonstrated good long-term outcomes with meniscal allograft transplantation, although the indications and techniques continue to evolve, and the long-term chondroprotective potential of this approach has yet to be determined. Several synthetic implants, most of which are approved in the European market, have shown some promise for replacing part of or the entire meniscus, including collagen meniscal implants, hydrogels, and polymer scaffolds. Currently, there is no ideal implant generated by means of tissue engineering. However, meniscus tissue engineering is a fast developing field that promises to develop an implant that mimics the histologic and biomechanical properties of a native meniscus.


Meniscus Meniscus repair Replacement Meniscal allograft Meniscus transplantation Review Biological therapies Knee injuries 



The authors thank M. Ferretti for his support and contribution to this paper.

Compliance with Ethics Guidelines

Conflict of Interest

Camila Cohen Kaleka, Pedro Debieux, Diego da Costa Astur, Gustavo Gonçalves Arliani, and Moisés Cohen declare that they have no conflict of interest.

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.


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

  1. 1.
    Englund M, Roos EM, Roos HP, Lohmander LS. Patient-relevant outcomes fourteen years after meniscectomy: influence of type of meniscal tear and size of resection. Rheumatology (Oxford). 2001;40:631–9.CrossRefGoogle Scholar
  2. 2.
    Fairbank TJ. Knee joint changes after meniscectomy. J Bone Joint Surg (Br). 1948;30B:664–70.Google Scholar
  3. 3.
    Lanzer WL, Komenda G. Changes in articular cartilage after meniscectomy. Clin Orthop Relat Res. 1990;252:41–8.PubMedGoogle Scholar
  4. 4.
    Noble J. Clinical features of the degenerate meniscus with the results of meniscectomy. Br J Surg. 1975;62:977–81.PubMedCrossRefGoogle Scholar
  5. 5.
    Roos H, Lauren M, Adalberth T, Roos EM, Jonsson K, Lohmander LS. Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after twenty-one years, compared with matched controls. Arthritis Rheum. 1998;41:687–93.PubMedCrossRefGoogle Scholar
  6. 6.
    McDevitt CA, Webber RJ. The ultrastructure and biochemistry of meniscal cartilage. Clin Orthop Relat Res. 1990;252:8–18.PubMedGoogle Scholar
  7. 7.
    Thompson WO, Thaete FL, Fu FH, Dye SF. Tibial meniscal dynamics using three-dimensional reconstruction of magnetic resonance images. Am J Sports Med. 1991;19:210–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Saamanen AM, Tammi M, Kiviranta I, Helminen HJ. Running exercise as a modulator of proteoglycan matrix in the articular cartilage of young rabbits. Int J Sports Med. 1988;9:127–33.PubMedCrossRefGoogle Scholar
  9. 9.
    Helfet AJ. Mechanism of derangements of the medial semilunar cartilage and their management. J Bone Joint Surg (Br). 1959;41-B:319–36.Google Scholar
  10. 10.••
    Vrancken ACT, Buma P, van Tienen TG. Synthetic meniscus replacement: a review. Int Orthop. 2013;37:291–9. This study consists of a literature review that points to interesting topics and is focused on the treatment of irreparable meniscal tears with synthetic menisci.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Sihvonen R, Paavola M, Malmivaara A, Itälä A, Joukainen A, Nurmi H, et al. Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group. Arthroscopic partial meniscectomy vs sham surgery for a degenerative meniscal tear. N Engl J Med. 2013;26:2515–24.CrossRefGoogle Scholar
  12. 12.
    Rubman MH, Noyes FR, Barber-Westin S. Arthroscopic repair of meniscal tears that extend into the avascular zone. A review of 198 single and complex tears. Am J Sports Med. 1998;26:87–95.PubMedGoogle Scholar
  13. 13.
    Ahn JH, Lee YS, Yoo JC, et al. Clinical and second-look arthroscopic evaluation of repaired medial meniscus in anterior cruciate ligament-reconstructed knees. Am J Sports Med. 2010;38:472–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Noyes FR, Barber-Westin SD. Meniscus tears: diagnosis, repair techniques, clinical outcomes. In: Noyes FR, editor. Noyes’ knee disorders: surgery, rehabilitation, clinical outcomes. Philadelphia: Saunders; 2009. p. 733–71.Google Scholar
  15. 15.
    Noyes FR, Heckmann TP, Barber-Westin SD. Meniscus repair and transplantation: a comprehensive update. J Orthop Sports Phys Ther. 2012;42:274–90.PubMedCrossRefGoogle Scholar
  16. 16.••
    Nepple JJ, Dunn WR, Wright RW. Meniscal repair outcomes at greater than five years: a systematic literature review and meta-analysis. J Bone Joint Surg Am. 2012;94:2222–7. A systematic review of the outcomes of meniscal repair from 13 studies demonstrated very similar rates of meniscal failure for all the techniques investigated.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.••
    Verdonk P, Beaufils P, Bellemans J, Djian P, Heinrichs EL, Huysse, et al. Successful treatment of painful irreparable partial meniscal defects with a polyurethane scaffold two-year safety and clinical outcomes. Am J Sports Med. 2012;40:844–53. This study is important because it presents the outcomes of a new option for the treatment of irreparable meniscal injuries. The study consists of a multicenter series of cases, with 52 patients treated with a new polyurethane scaffold exhibiting good results in a 2-year follow-up.PubMedCrossRefGoogle Scholar
  18. 18.
    Kon E, Filardo G, Zaffagnini S, Di Martino A, Di Matteo B, Muccioli GMM, et al. Biodegradable polyurethane meniscal scaffold for isolated partial lesions or as combined procedure for knees with multiple comorbidities: clinical results at 2 years. Knee Surg Sports Traumatol Arthrosc. 2014;22:128–34.PubMedCrossRefGoogle Scholar
  19. 19.
    Mouzopoulos G, Siebold R. Partial meniscus substitution with tissue-engineered scaffold: an overview. Clin Sports Med. 2012;31:167–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Silver FH, Pins G. Cell growth on collagen: a review of tissue engineering using scaffolds containing extracellular matrix. J Long-Term Eff Med Implants. 1992;2:67–80.PubMedGoogle Scholar
  21. 21.
    Gastel JA, Muirhead WR, Lifrak JT, Fadale PD, Hulstyn MJ, Labrador DP. Meniscal tissue regeneration using a collagenous biomaterial derived from porcine small intestine submucosa. Arthroscopy. 2001;17:151–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Steadman JR, Rodkey WG, Li S-T. The collagen meniscus implant. Development of a prosthetic meniscal replacement. In: Mow VC, Arnoczky SP, Jackson DJ, editors. Knee meniscus: basic and clinical foundation. New York: Raven Press; 1992. p. 165–73.Google Scholar
  23. 23.
    Welch JA, Montgomery RD, Lenz SD, Plouhar P, Shelton WR. Evaluation of small-intestinal submucosa implants for repair of meniscal defects in dogs. Am J Vet Res. 2002;63:427–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Stone KR, Steadman JR, Rodkey WG, et al. Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data. J Bone Joint Surg Am. 1997;79:1770–7.PubMedGoogle Scholar
  25. 25.
    Zaffagnini S, Giordano G, Vascellari A, Bruni D, Neri MP, Iacono F, et al. Arthroscopic collagen meniscus implant results at 6 to 8 years follow up. Knee Surg Sports Traumatol Arthrosc. 2007;15:175–83.PubMedCrossRefGoogle Scholar
  26. 26.••
    Zaffagnini S, Marcheggiani Muccioli GM, Lopomo N, et al. Prospective long-term outcomes of the medial collagen meniscus implant vs partial medial meniscectomy: a minimum 10-year follow-up study. Am J Sports Med. 2011;39:977–85. This study consists of a prospective cohort of 33 patients treated with CMI for irreparable meniscal lesions demonstrating good outcomes after a 10-year follow-up.PubMedCrossRefGoogle Scholar
  27. 27.
    Rodkey WG, DeHaven KE, Montgomery III WH, Baker Jr CL, Beck Jr CL, Hormel SE, et al. Comparison of the collagen meniscus implant with partial meniscectomy. A prospective randomized trial. J Bone Joint Surg Am. 2008;90:1413–26.PubMedCrossRefGoogle Scholar
  28. 28.
    Spencer SJ, Saithna A, Carmont MR, et al. Meniscal scaffolds: early experience and review of the literature. Knee. 2012;19:760–5.PubMedCrossRefGoogle Scholar
  29. 29.•
    Verdonk R, Verdonk P, Huysse W, Forsyth R, Heinrichs E. Tissue ingrowth after implantation of a novel, biodegradable polyurethane scaffold for treatment of partial meniscal lesions. Am J Sports Med. 2011;39:774–82. This study consists of a case series of 52 patients, which shows the proper integration of the polyurethane scaffold with the native meniscal tissue, as well as tissue ingrowth within this scaffold.PubMedCrossRefGoogle Scholar
  30. 30.••
    De Coninck T, Huysse W, Willemot L, Verdonk R, Verstraete K, Verdonk P. Two-year follow-up study on clinical and radiological outcomes of polyurethane meniscal scaffolds. Am J Sports Med. 2013;41:64–72. This is the first study to correlate the radial displacement of the scaffold measured via MRI with clinical outcomes, and it concludes that there is no correlation between the scaffold displacement and the clinical outcome score, either pre- or postoperatively.PubMedCrossRefGoogle Scholar
  31. 31.
    Zuidema J, van Minnen B, Span MM, Hissink CE, van Kooten TG, Bos RR. In vitro degradation of a biodegradable polyurethane foam, based on 1,4-butanediisocyanate: a three-year study at physiological and elevated temperature. J Biomed Mater Res A. 2009;90:920–30.PubMedCrossRefGoogle Scholar
  32. 32.••
    Elattar M, Dhollander A, Verdonk R, et al. Twenty-six years of meniscal allograft transplantation: is it still experimental? A meta-analysis of 44 trials. Knee Surg Sports Traumatol Arthrosc. 2011;19:147–57. This meta-analysis demonstrates satisfactory outcomes after meniscal allograft transplantation; the procedure was considered safe and reliable for the treatment of refractory postmeniscectomy symptoms in selected patients.PubMedCrossRefGoogle Scholar
  33. 33.
    Lee AS, Kang RW, Kroin E, Verma NN, Cole BJ. Allograft meniscus transplantation. Sports Med Arthrosc Rev. 2012;20:106–14.CrossRefGoogle Scholar
  34. 34.
    Packer JD, Rodeo SA. Meniscal allograft transplantation. Clin Sports Med. 2009;28:259–83.PubMedCrossRefGoogle Scholar
  35. 35.
    Lee SR, Kim JG, Nam SW. The tips and pitfalls of meniscus allograft transplantation. Knee Surg Relat Res. 2012;24:137–45.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Brophy R, Matava MJ. Surgical options for meniscal replacement. J Am Acad Orthop Surg. 2012;20:265–72.PubMedCrossRefGoogle Scholar
  37. 37.
    Lubowitz JH, Verdonk PC, Reid III JB, Verdonk R. Meniscus allograft transplantation: a current concepts review. Knee Surg Sports Traumatol Arthrosc. 2007;15:476–92.PubMedCrossRefGoogle Scholar
  38. 38.
    Van Thiel GS, Verma N, Yanke A, Basu S, Farr J, Cole B. Meniscal allograft size can be predicted by height, weight, and gender. Arthroscopy. 2009;25:722–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Pollard ME, Kang Q, Berg EE. Radiographic sizing for meniscal transplantation. Arthroscopy. 1995;11:684–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Yoon JR, Kim TS, Lim HC, Lim HT, Yang JH. Is radiographic measurement of bony landmarks reliable for lateral meniscal sizing? Am J Sports Med. 2011;39:582–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Verdonk PC, Demurie A, Almqvist KF, Veys EM, Verbruggen G, Verdonk R. Transplantation of viable meniscal allografts: survivorship analysis and clinical outcome of one hundred cases. J Bone Joint Surg Am. 2005;87:715–24.PubMedCrossRefGoogle Scholar
  42. 42.
    Cole BJ, Dennis MG, Lee SJ, et al. Prospective evaluation of allograft meniscus transplantation: a minimum 2-year follow-up. Am J Sports Med. 2006;34:919–27.PubMedCrossRefGoogle Scholar
  43. 43.••
    Vangsness Jr CT, Farr II J, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014;96:90–8. A multicenter study evaluating 55 patients who underwent a partial meniscectomy; patients treated with mesenchymal stem cells were compared with a control group. Although not definitive, the study presents a good outcome over time.PubMedCrossRefGoogle Scholar
  44. 44.
    Zellner J, Mueller M, Berner A, Dienstknecht T, Kujat R, Nerlich M, et al. Role of mesenchymal stem cells in tissue engineering of meniscus. J Biomed Mater Res A. 2010;94:1150–61.PubMedGoogle Scholar
  45. 45.
    Liu C, Toma IC, Mastrogiacomo M, Krettek C, von Lewinski G, Jagodzinski M. Meniscus reconstruction: today's achievements and premises for the future. Arch Orthop Trauma Surg. 2013;133:95–109.PubMedCrossRefGoogle Scholar
  46. 46.
    Ishida K, Kuroda R, Miwa M, et al. The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. Tissue Eng. 2007;13:1103–12.PubMedCrossRefGoogle Scholar
  47. 47.
    Braun HJ, Wasterlain AS, Dragoo JL. The use of PRP in ligament and meniscal healing. Sports Med Arthrosc. 2013;21:206–12.PubMedCrossRefGoogle Scholar
  48. 48.
    Goto H, Shuler FD, Niyibizi C, Fu FH, Robbins PD, Evans CH. Gene therapy for meniscal injury: enhanced synthesis of proteoglycan and collagen by meniscal cells transduced with a TGFbeta (1) gene. Osteoarthr Cartil. 2000;8:266–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Hidaka C, Ibarra C, Hannafin JA, Torzilli PA, Quitoriano M, Jen SS, et al. Formation of vascularized meniscal tissue by combining gene therapy with tissue engineering. Tissue Eng. 2002;8:93–105.PubMedCrossRefGoogle Scholar
  50. 50.
    Scotti C, Hirschmann MT, Antinolfi P, Martin I, Peretti GM. Meniscus repair and regeneration: review on current methods and research potential. Eur Cell Mater. 2013;26:150–70.PubMedGoogle Scholar
  51. 51.
    de Mulder EL, Hannink G, Giele M, Verdonschot N, Buma P. Proliferation of meniscal fibrochondrocytes cultured on a new polyurethane scaffold is stimulated by TGF-β. J Biomater Appl. 2013;27:617–26.PubMedCrossRefGoogle Scholar
  52. 52.•
    de Girolamo L, Galliera E, Volpi P, Denti M, Dogliotti G, Quaglia A, et al. Why menisci show higher healing rate when repaired during ACL reconstruction? Growth factors release can be the explanation. Knee Surg Sports Traumatol Arthrosc. 2013; [Epub ahead of print]. The authors try to find a difference between the concentration of the growth factors in the knee joint, with and without ACL reconstruction, to find out why meniscus repair has better outcomes with this concomitant surgery. Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Camila Cohen Kaleka
    • 1
    • 2
    Email author
  • Pedro Debieux
    • 2
    • 3
  • Diego da Costa Astur
    • 2
    • 4
  • Gustavo Gonçalves Arliani
    • 2
    • 4
  • Moisés Cohen
    • 2
    • 5
  1. 1.Department of OrthopedicsKnee Surgery Division of the Santa Casa School of Medicine and Hospitals of São PauloSão PauloBrazil
  2. 2.Cohen’s Institute of Orthopedics and RehabilitationSão PauloBrazil
  3. 3.Orthopedics DepartmentKnee Arthroscopy Division of the Federal University of São PauloSão PauloBrazil
  4. 4.Department of Orthopedics–Knee Surgery DivisionTraumatology and Sports Division of the Federal University of São PauloSão PauloBrazil
  5. 5.Department of Orthopedics of the Federal University of São PauloSão PauloBrazil

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