Skip to main content

Advanced Regenerative Strategies for Human Knee Meniscus

  • Chapter
  • First Online:
Regenerative Strategies for the Treatment of Knee Joint Disabilities

Abstract

The meniscus tissue has important roles in the function and biomechanics of the knee. Despite the great advances in the treatment of meniscus lesions, the clinical need is still not fulfilled. To overcome the challenges of regeneration, tissue engineering-based strategies have been attempted with limited success. The process of meniscus tissue regeneration is very complex and has many parameters that are evident only to a certain degree. Today, the regenerative strategies have been advancing beyond the traditional tissue engineering concept by growing the utilization of the expertises of complementary areas that include, but not limited to, bioreactor engineering, bioprinting coupled to reverse engineering, biology, nanotechnology and gene therapy approaches. Herein, the recent reported advanced strategies involving bioreactors, self-assembling process, and somatic gene therapy for meniscus regeneration are overviewed.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Allen AA, Caldwell GL Jr, Fu FH (1995) Anatomy and biomechanics of the meniscus. Oper Tech Orthop 5(1):2–9

    Article  Google Scholar 

  2. McDermott ID, Masouros SD, Amis AA (2008) Biomechanics of the menisci of the knee. Curr Orthop 22(3):193–201

    Article  Google Scholar 

  3. Fetzer GB, Spindler KP, Amendola A, Andrish JT, Bergfeld JA, Dunn WR, Flanigan DC, Jones M, Kaeding CC, Marx RG (2009) Potential market for new meniscus repair strategies: evaluation of the MOON cohort. J Knee Surg 22(3):180

    Article  Google Scholar 

  4. Tudor F, McDermott ID, Myers P (2014) Meniscal repair: a review of current practice. Orthop Trauma 28(2):88–96

    Article  Google Scholar 

  5. Fairbank T (1948) Knee joint changes after meniscectomy. J Bone Joint Surg Br 30(4):664–670

    Google Scholar 

  6. McDermott I, Amis A (2006) The consequences of meniscectomy. J Bone Joint Surg Br 88(12):1549–1556

    Article  Google Scholar 

  7. Mordecai SC, Al-Hadithy N, Ware HE, Gupte CM (2014) Treatment of meniscal tears: an evidence based approach. World J Orthop 5(3):233

    Article  Google Scholar 

  8. Arnoczky SP, Warren RF (1982) Microvasculature of the human meniscus. Am J Sports Med 10(2):90–95

    Article  Google Scholar 

  9. Makris EA, Hadidi P, Athanasiou KA (2011) The knee meniscus: structure–function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials 32(30):7411–7431

    Article  Google Scholar 

  10. Scotti C, Hirschmann MT, Antinolfi P, Martin I, Peretti GM (2013) Meniscus repair and regeneration: review on current methods and research potential. Eur Cells Mater 26:150–170

    Google Scholar 

  11. Pereira H, Frias AM, Oliveira JM, Espregueira-Mendes J, Reis RL (2011) Tissue engineering and regenerative medicine strategies in meniscus lesions. Arthroscopy 27(12):1706–1719

    Article  Google Scholar 

  12. Kang SW, Sun-Mi S, Jae-Sun L, Eung-Seok L, Kwon-Yong L, Sang-Guk P, Jung-Ho P, Byung-Soo K (2006) Regeneration of whole meniscus using meniscal cells and polymer scaffolds in a rabbit total meniscectomy model. J Biomed Mater Res Part A 77(4):659–671

    Article  Google Scholar 

  13. Zellner J, Mueller M, Berner A, Dienstknecht T, Kujat R, Nerlich M, Hennemann B, Koller M, Prantl L, Angele M (2010) Role of mesenchymal stem cells in tissue engineering of meniscus. J Biomed Mater Res Part A 94(4):1150–1161

    Google Scholar 

  14. Stone KR, Rodkey WG, Webber R, McKinney L, Steadman JR (1992) Meniscal regeneration with copolymeric collagen scaffolds in vitro and in vivo studies evaluated clinically, histologically, and biochemically. Am J Sports Med 20(2):104–111

    Article  Google Scholar 

  15. Verdonk R, Verdonk P, Huysse W, Forsyth R, Heinrichs E-L (2011) Tissue ingrowth after implantation of a novel, biodegradable polyurethane scaffold for treatment of partial meniscal lesions. Am J Sports Med 39(4):774–782

    Article  Google Scholar 

  16. Gu Y, Wang Y, Dai H, Lu L, Cheng Y, Zhu W (2012) Chondrogenic differentiation of canine myoblasts induced by cartilage-derived morphogenetic protein-2 and transforming growth factor-β1 in vitro. Mol Med Rep 5(3):767–772

    Google Scholar 

  17. Ishida K, Kuroda R, Miwa M, Tabata Y, Hokugo A, Kawamoto T, Sasaki K, Doita M, Kurosaka M (2007) The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. Tissue Eng 13(5):1103–1112

    Article  Google Scholar 

  18. Ballyns JJ, Wright TM, Bonassar LJ (2010) Effect of media mixing on ECM assembly and mechanical properties of anatomically-shaped tissue engineered meniscus. Biomaterials 31(26):6756–6763

    Article  Google Scholar 

  19. Puetzer JL, Ballyns JJ, Bonassar LJ (2012) The effect of the duration of mechanical stimulation and post-stimulation culture on the structure and properties of dynamically compressed tissue-engineered menisci. Tissue Eng Part A 18(13–14):1365–1375

    Article  Google Scholar 

  20. 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(1):95–109

    Article  Google Scholar 

  21. Pereira H, Silva-Correia J, Oliveira J, Reis R, Espregueira-Mendes J (2013) Future trends in the treatment of meniscus lesions: from repair to regeneration. In: Verdonk R, Espregueira-Mendes J, Monllau JC (eds) Meniscal transplantation. Springer, Berlin, pp 103–112

    Google Scholar 

  22. Oliveira J, Pereira H, Yan L, Silva-Correia J, Oliveira A, Espregueira-Mendes J, Reis R (2013) Scaffold that enables segmental vascularization for the engineering of complex tissues and methods of making the same, PT Patent 106174, Priority date: 161/2013, 26-08-2013

    Google Scholar 

  23. Zhong J-J (2010) Recent advances in bioreactor engineering. Korean J Chem Eng 27(4):1035–1041

    Article  Google Scholar 

  24. Wang D, Liu W, Han B, Xu R (2005) The bioreactor: a powerful tool for large-scale culture of animal cells. Curr Pharm Biotechnol 6(5):397–403

    Article  Google Scholar 

  25. Hansmann J, Groeber F, Kahlig A, Kleinhans C, Walles H (2013) Bioreactors in tissue engineering—principles, applications and commercial constraints. Biotechnol J 8(3):298–307

    Article  Google Scholar 

  26. Pörtner R, Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM (2005) Bioreactor design for tissue engineering. J Biosci Bioeng 100(3):235–245

    Article  Google Scholar 

  27. Martin Y, Vermette P (2005) Bioreactors for tissue mass culture: design, characterization, and recent advances. Biomaterials 26(35):7481–7503

    Article  Google Scholar 

  28. Neves AA, Medcalf N, Brindle KM (2005) Influence of stirring-induced mixing on cell proliferation and extracellular matrix deposition in meniscal cartilage constructs based on polyethylene terephthalate scaffolds. Biomaterials 26(23):4828–4836

    Article  Google Scholar 

  29. Neves AA, Medcalf N, Brindle K (2003) Functional assessment of tissue-engineered meniscal cartilage by magnetic resonance imaging and spectroscopy. Tissue Eng 9(1):51–62

    Article  Google Scholar 

  30. Marsano A, Wendt D, Quinn T, Sims T, Farhadi J, Jakob M, Heberer M, Martin I (2006) Bi-zonal cartilaginous tissues engineered in a rotary cell culture system. Biorheology 43(3):553–560

    Google Scholar 

  31. Petri M, Ufer K, Toma I, Becher C, Liodakis E, Brand S, Haas P, Liu C, Richter B, Haasper C (2012) Effects of perfusion and cyclic compression on in vitro tissue engineered meniscus implants. Knee Surg Sports Traumatol Arthrosc 20(2):223–231

    Article  Google Scholar 

  32. Fox DB, Warnock JJ, Stoker AM, Luther JK, Cockrell M (2010) Effects of growth factors on equine synovial fibroblasts seeded on synthetic scaffolds for avascular meniscal tissue engineering. Res Vet Sci 88(2):326–332

    Article  Google Scholar 

  33. Aufderheide AC, Athanasiou KA (2005) Comparison of scaffolds and culture conditions for tissue engineering of the knee meniscus. Tissue Eng 11(7–8):1095–1104

    Article  Google Scholar 

  34. Gunja NJ, Athanasiou KA (2010) Effects of hydrostatic pressure on leporine meniscus cell-seeded PLLA scaffolds. J Biomed Mater Res Part A 92(3):896–905

    Google Scholar 

  35. Gunja NJ, Uthamanthil RK, Athanasiou KA (2009) Effects of TGF-β1 and hydrostatic pressure on meniscus cell-seeded scaffolds. Biomaterials 30(4):565–573

    Article  Google Scholar 

  36. Weinand C, Xu JW, Peretti GM, Bonassar LJ, Gill TJ (2009) Conditions affecting cell seeding onto three-dimensional scaffolds for cellular-based biodegradable implants. J Biomed Mater Res B Appl Biomater 91(1):80–87

    Article  Google Scholar 

  37. McNulty AL, Estes BT, Wilusz RE, Weinberg JB, Guilak F (2010) Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1. Osteoarthr Cartil 18(6):830–838

    Article  Google Scholar 

  38. Ballyns JJ, Bonassar LJ (2011) Dynamic compressive loading of image-guided tissue engineered meniscal constructs. J Biomech 44(3):509–516

    Article  Google Scholar 

  39. Martínez H, Brackmann C, Enejder A, Gatenholm P (2012) Mechanical stimulation of fibroblasts in micro-channeled bacterial cellulose scaffolds enhances production of oriented collagen fibers. J Biomed Mater Res Part A 100(4):948–957

    Article  Google Scholar 

  40. Liu C, Abedian R, Meister R, Haasper C, Hurschler C, Krettek C, von Lewinski G, Jagodzinski M (2012) Influence of perfusion and compression on the proliferation and differentiation of bone mesenchymal stromal cells seeded on polyurethane scaffolds. Biomaterials 33(4):1052–1064

    Article  Google Scholar 

  41. Connelly JT, Vanderploeg EJ, Mouw JK, Wilson CG, Levenston ME (2010) Tensile loading modulates bone marrow stromal cell differentiation and the development of engineered fibrocartilage constructs. Tissue Eng Part A 16(6):1913–1923

    Article  Google Scholar 

  42. Upton ML, Chen J, Guilak F, Setton LA (2003) Differential effects of static and dynamic compression on meniscal cell gene expression. J Orthop Res 21(6):963–969

    Article  Google Scholar 

  43. Ferretti M, Madhavan S, Deschner J, Rath-Deschner B, Wypasek E, Agarwal S (2006) Dynamic biophysical strain modulates proinflammatory gene induction in meniscal fibrochondrocytes. Am J Physiol Cell Physiol 290(6):C1610–C1615

    Article  Google Scholar 

  44. Pereira H, Caridade SG, Frias AM, Silva-Correia J, Pereira DR, Cengiz IF, Mano JF, Oliveira JM, Espregueira-Mendes J, Reis RL (2014) Biomechanical and cellular segmental characterization of human meniscus: building the basis for tissue engineering therapies. Osteoarthr Cartil 22(9):1271–1281

    Article  Google Scholar 

  45. Athanasiou KA, Eswaramoorthy R, Hadidi P, Hu JC (2013) Self-organization and the self-assembling process in tissue engineering. Annu Rev Biomed Eng 15:115–136

    Article  Google Scholar 

  46. Hu JC, Athanasiou KA (2006) A self-assembling process in articular cartilage tissue engineering. Tissue Eng 12(4):969–979

    Article  Google Scholar 

  47. Araujo V, Figueiredo C, Joazeiro P, Mora O, Toledo O (2002) In vitro rapid organization of rabbit meniscus fibrochondrocytes into chondro-like tissue structures. J Submicrosc Cytol Pathol 34(3):335–343

    Google Scholar 

  48. Hoben GM, Athanasiou KA (2008) Creating a spectrum of fibrocartilages through different cell sources and biochemical stimuli. Biotechnol Bioeng 100(3):587–598

    Article  Google Scholar 

  49. Hoben GM, Hu JC, James RA, Athanasiou KA (2007) Self-assembly of fibrochondrocytes and chondrocytes for tissue engineering of the knee meniscus. Tissue Eng 13(5):939–946

    Article  Google Scholar 

  50. Aufderheide AC, Athanasiou KA (2007) Assessment of a bovine co-culture, scaffold-free method for growing meniscus-shaped constructs. Tissue Eng 13(9):2195–2205

    Article  Google Scholar 

  51. MacBarb RF, Makris EA, Hu JC, Athanasiou KA (2013) A chondroitinase-ABC and TGF-β1 treatment regimen for enhancing the mechanical properties of tissue-engineered fibrocartilage. Acta Biomater 9(1):4626–4634

    Article  Google Scholar 

  52. Huey DJ, Athanasiou KA (2011) Tension-compression loading with chemical stimulation results in additive increases to functional properties of anatomic meniscal constructs. PLoS ONE 6(11):e27857

    Article  Google Scholar 

  53. 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(8):2052–2058

    Article  Google Scholar 

  54. Adachi N, Pelinkovic D, Lee CW, Fu FH, Huard J (2001) Gene therapy and the future of cartilage repair. Oper Tech Orthop 11(2):138–144

    Article  Google Scholar 

  55. Chen Y (2001) Orthopedic applications of gene therapy. J Orthop Sci 6(2):199–207

    Article  Google Scholar 

  56. Evans C (1995) Current concepts review: possible orthopaedic applications of gene therapy. J Bone Joint Surg Am 77(7):1103–1114

    Google Scholar 

  57. Evans C, Ghivizzani S, Robbins P (2012) Orthopedic gene therapy—lost in translation? J Cell Physiol 227(2):416–420

    Article  Google Scholar 

  58. Evans C, Ghivizzani S, Smith P, Shuler F, Mi Z, Robbins P (2000) Using gene therapy to protect and restore cartilage. Clin Orthop Rel Res (379 Suppl):S214

    Google Scholar 

  59. Giannoudis PV, Tzioupis CC, Tsirids E (2006) Gene therapy in orthopaedics. Injury 37(1):S30–S40

    Article  Google Scholar 

  60. Anderson WF (1998) Human gene therapy. Nature 392(6679):25

    Google Scholar 

  61. Kaufmann KB, Büning H, Galy A, Schambach A, Grez M (2013) Gene therapy on the move. EMBO Mol Med 5(11):1642–1661

    Article  Google Scholar 

  62. Babensee JE, McIntire LV, Mikos AG (2000) Growth factor delivery for tissue engineering. Pharm Res 17(5):497–504

    Article  Google Scholar 

  63. Nimni M (1997) Polypeptide growth factors: targeted delivery systems. Biomaterials 18(18):1201–1225

    Article  Google Scholar 

  64. Bhargava MM, Attia ET, Murrell GA, Dolan MM, Warren RF, Hannafin JA (1999) The effect of cytokines on the proliferation and migration of bovine meniscal cells. Am J Sports Med 27(5):636–643

    Google Scholar 

  65. 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 13(1):19–28

    Article  Google Scholar 

  66. Musumeci G, Loreto C, Carnazza ML, Cardile V, Leonardi R (2012) Acute injury affects lubricin expression in knee menisci. An immunohistochemical study. Ann Anatomy Anat Anz 95(2):151–158

    Google Scholar 

  67. Jones A, Flannery C (2007) Bioregulation of lubricin expression by growth factors and cytokines. Eur Cells Mater 13:40

    Google Scholar 

  68. Hennerbichler A, Moutos FT, Hennerbichler D, Weinberg JB, Guilak F (2007) Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine meniscus in vitro. Osteoarthr Cartil 15(9):1053–1060

    Article  Google Scholar 

  69. Goto H, Shuler FD, Lamsam C, Moller HD, Niyibizi C, Fu FH, Robbins PD, Evans CH (1999) Transfer of LacZ marker gene to the meniscus. J Bone Joint Surg 81(7):918–925

    Google Scholar 

  70. Madry H, Cucchiarini M, Kaul G, Kohn D, Terwilliger EF, Trippel SB (2004) Menisci are efficiently transduced by recombinant adeno-associated virus vectors in vitro and in vivo. Am J Sports Med 32(8):1860–1865

    Article  Google Scholar 

  71. Cucchiarini M, Schetting S, Terwilliger E, Kohn D, Madry H (2009) rAAV-mediated overexpression of FGF-2 promotes cell proliferation, survival, and α-SMA expression in human meniscal lesions. Gene Ther 16(11):1363–1372

    Article  Google Scholar 

  72. Hidaka C, Ibarra C, Hannafin JA, Torzilli PA, Quitoriano M, Jen S-S, Warren RF, Crystal RG (2002) Formation of vascularized meniscal tissue by combining gene therapy with tissue engineering. Tissue Eng 8(1):93–105

    Article  Google Scholar 

  73. Martinek V, Usas A, Pelinkovic D, Robbins P, Fu FH, Huard J (2002) Genetic engineering of meniscal allografts. Tissue Eng 8(1):107–117

    Article  Google Scholar 

  74. Steinert AF, Palmer GD, Capito R, Hofstaetter JG, Pilapil C, Ghivizzani SC, Spector M, Evans CH (2007) Genetically enhanced engineering of meniscus tissue using ex vivo delivery of transforming growth factor-β1 complementary deoxyribonucleic acid. Tissue Eng 13(9):2227–2237

    Article  Google Scholar 

  75. Bonadio J (2000) Tissue engineering via local gene delivery. J Mol Med 78(6):303–311

    Article  Google Scholar 

  76. Goto H, Shuler F, Niyibizi C, Fu F, Robbins P, Evans C (2000) Gene therapy for meniscal injury: enhanced synthesis of proteoglycan and collagen by meniscal cells transduced with a TGFβ1 gene. Osteoarthr Cartil 8(4):266–271

    Article  Google Scholar 

  77. Zhang H, Leng P, Zhang J (2009) Enhanced meniscal repair by overexpression of hIGF-1 in a full-thickness model. Clin Orthop Relat Res 467(12):3165–3174

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank to the financial support of the MultiScaleHuman project (Contract number: MRTN-CT-2011-289897) in the Marie Curie Actions—Initial Training Networks. I. F. Cengiz thanks the Portuguese Foundation for Science and Technology (FCT) for the Ph.D. scholarship (SFRH/BD/99555/2014). J. M. Oliveira also thanks to the FCT for the funds provided to under the program Investigador FCT 2012 (IF/00423/2012).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ibrahim Fatih Cengiz .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Cengiz, I.F., Silva-Correia, J., Pereira, H., Espregueira-Mendes, J., Oliveira, J.M., Reis, R.L. (2017). Advanced Regenerative Strategies for Human Knee Meniscus. In: Oliveira, J., Reis, R. (eds) Regenerative Strategies for the Treatment of Knee Joint Disabilities. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-319-44785-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-44785-8_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-44783-4

  • Online ISBN: 978-3-319-44785-8

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics