Abstract
Menisci represent fundamental structures for the maintenance of knee homeostasis, playing a key role in knee biomechanics. However, their intrinsic regenerative potential is poor. As a consequence, when a lesion occurs and the meniscus is partially removed by surgery, knee mechanics is subject to dramatic changes. These have been demonstrated to lead often to the development of early osteoarthritis. Therefore, menisci should be repaired whenever possible. In the last decades, tissue engineering approaches have been advocated to improve the reparative processes of joint tissues. In this study, the bonding capacity of an articular chondrocytes-fibrin glue hydrogel was tested as a biologic glue to improve the bonding between two swine meniscal slices in a nude mouse model. The composites were wrapped with acellular fibrin glue and implanted in subcutaneous pouches of nude mice for 4 weeks. Upon retrieval, a firm gross bonding was observed in the experimental samples while none of the control samples, prepared with acellular fibrin glue at the interface, presented any sign of bonding. This was consistent with the histological and scanning electron microscope findings. In particular, a fibrocartilaginous tissue was found at the interface between the meniscal slices, partially penetrating the native meniscus tissue. In order to overcome the lack of regenerative properties of the meniscus, the rationale of using cellular fibrin glue is that fibrin provides immediate stability while carrying cells in the site of lesion. Moreover, fibrin gel is recognized as an optimal scaffold for cell embedding and for promoting fibrocartilaginous differentiation of the cells which synthesize matrix having healing property. These results demonstrated the potential of this model for improving the meniscal bonding. However, further orthotopic studies in a large animal model are needed to evaluate its potential for clinical application.
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References
Ahmed AM, Burke DL (1983) In vitro measurement of static pressure distribution in synovial joints: Part I. Tibial surface of the knee. J Biomech Eng 105:216–225
Allen PR, Denham RA, Swan AV (1984) Late degenerative changes after meniscectomy: factors affecting the knee after operation. J Bone Joint Surg 66B:666–671
Appel H (1970) Late results after meniscectomy in the knee joint: a clinical and roentgenologic follow up investigation. Acta Orthop Scand 133(Suppl):1–111
Arnoczky SP, Warren RF (1982) Microvasculature of the human meniscus. Am J Sports Med 10:90–95
Arnoczky SP, Warren RF (1983) The microvasculature of the meniscus and its response to injury: An experimental study in the dog. Am J Sports Med 11:131–141
Berjon JJ, Munuera L, Calvo M (1991) Degenerative lesions in the articular cartilage after meniscectomy: Preliminary experimental study in dogs. J Trauma 31:342–350
Bland Sutton J (1897) Ligaments, their nature and morphology, 2nd edn. HK Lewis, London
Bryant D, Dill J, Litchfield R, Amendola A, Giffin R, Fowler P, Kirkley A (2007) Effectiveness of bioabsorbable arrows compared with inside-out suturing for vertical, reparable meniscal lesions: a randomized clinical trial. Am J Sports Med 35(6):889–896
Chiari C, Koller U, Dorotka R, Eder C, Plasenzotti R, Lang S, Ambrosio L, Tognana E, Kon E, Salter D, Nehrer S (2006) A tissue engineering approach to meniscus regeneration in a sheep model. Osteoarthritis Cartilage 14(10):1056–1065
Gear MW (1967) The late results of meniscectomy. Br J Surg 54:270–272
Ghosh P, Sutherland J, Bellenger C, Read R, Darvodelsky A (1990) The influence of weightbearing exercise on articular cartilage of meniscectomized joints: an experimental study in sheep. Clin Orthop 252:101–113
Hargreaves DJ, Seedhom BB (1979) On the “bucket-handle” tear: Partial or total meniscectomy? A quantitative study. J Bone Joint Surg 61B:381
Hoch DH, Grodzinsky AJ, Koob TJ, Albert ML, Eyre DR (1983) Early changes in material properties of rabbit articular cartilage after meniscectomy. J Orthop Res 1:4–12
Ibarra C, Janetta C, Vacanti CA et al (1997) Tissue engineered meniscus: a potential new alternative to allogeneic meniscus transplantation. Transplant Proc 29:986–988
Ibarra C, Koski JA, Warren RF (2000) Tissue engineering meniscus: cells and matrix. Orthop Clin North Am 31:411–418
King D (1936) The function of semilunar cartilages. J Bone Joint Surg 18:1069–1076
King D (1936) The healing of semilunar cartilages. J Bone Joint Surg 18:333–342
Kon E, Chiari C, Marcacci M, Delcogliano M, Salter DM, Martin I, Ambrosio L, Fini M, Tschon M, Tognana E, Plasenzotti R, Nehrer S (2008) Tissue engineering for total meniscal substitution: animal study in sheep model. Tissue Eng Part A 14(6):1067–1080
Krause WR, Pope HM, Johnson RJ, Wilder DG (1976) Mechanical changes in the knee after meniscectomy. J Bone Joint Surg Am 58A:599–604
Levy IM, Torzilli PA, Gould JD, Warren RF (1989) The effect of lateral meniscectomy on motion of the knee. J Bone Joint Surg Am 71A:401–406
Lufti AM (1975) Morphological changes in the articular cartilage after meniscectomy: An experimental study in the monkey. J Bone Joint Surg 57B:525–528
Malicev E, Radosavljevic D, Velikonja NK (2007) Fibrin gel improved the spatial uniformity and phenotype of human chondrocytes seeded on collagen scaffolds. Biotechnol Bioeng 1;96(2):364–70
Marsano A, Wendt D, Raiteri R, Gottardi R, Stolz M, Wirz D, Daniels AU, Salter D, Jakob M, Quinn TM, Martin I (2006) Use of hydrodynamic forces to engineer cartilaginous tissues resembling the non-uniform structure and function of meniscus. Biomaterials 27(35):5927–5934
Northmore-Ball MD, Dandy DJ (1982) Long term results of arthroscopic partial meniscectomy. Clin Orthop 167:34–42
Peretti GM, Randolph MA, Caruso EM, Rossetti F, Zaleske DJ (1998) Bonding of cartilaginous matrices with cultured chondrocytes: an experimental model. J Orthop Res 16(1):89–95
Peretti GM, Bonassar LJ, Caruso EM, Randolph MA, Zaleske DJ (1999) Biomechanical analysis of a cell-based model for articular cartilage repair. Tissue Eng 5(4):317–326
Peretti GM, Caruso EM, Randolph MA, Zaleske DJ (2001) Meniscal fracture repair using engineered tissue. J Orthop Res 19:278–285
Peretti GM, Zaporojan V, Spangenberg KM, Randolph MA, Fellers J, Bonassar LJ (2003) Cell-based bonding of articular cartilage: an extended study. J Biomed Mater Res A 64(3):517–524
Peretti GM, Gill TJ, Xu JW, Randolph MA, Morse KR, Zaleske DJ (2004) Cell-based therapy for meniscal repair: a large animal study. Am J Sports Med 32(1):146–158
Peretti GM, Xu JW, Bonassar LJ, Kirchhoff CH, Yaremchuk MJ, Randolph MA (2006) Review of injectable cartilage engineering using fibrin gel in mice and swine models. Tissue Eng 12(5):1151–1168
Peretti GM, Randolph MA (2006) Meniscal fracture repair and implants using engineered tissue. In: Zanasi S, Brittberg M, Marcacci M (eds) Basic science, clinical repair and reconstruction of articular cartilage defects: current status and prospects. Timeo Editore, Bologna
Peretti GM, Zaporojan V, Fellers J, Montaruli A, Randolph MA, Bonassar LJ (2007) In vitro bonding of pre-seeded chondrocytes. Sport Sci Health 2(1):29–33
Peretti GM, Scotti C, Pozzi A, Mangiavini L, Vitari F, Domeneghini C, Fraschini G (2008) Bonding of meniscal tissue: a nude mouse repair model. Sport Sci Health 3(3):47–52
Shelbourne KD, Carr DR (2003) Meniscal repair compared with meniscectomy for bucket-handle medial meniscal tears in the anterior cruciate ligament-repaired knee. Am J Sports Med 31(5):718–723
Siebold R, Dehler C, Boes L, Ellermann A (2007) Arthroscopic all-inside repair using the meniscus arrow: long-term clinical follow-up of 113 patients. Arthroscopy 23(4):394–399
Sommerlath KG (1991) Results of meniscal repair and partial meniscectomy in stable knees. Int Orthop 15:347–350
Spotnitz WD, Burks S (2008) Hemostats, sealants, and adhesives: components of the surgical toolbox. Transfusion 48(7):1502–1516
Tapper EM, Hoover NW (1969) Late results after meniscectomy. J Bone Joint Surg 51A:517–526
Tielinen L, Lindahl J, Koskinen S, Hirvensalo E (2007) Clinical and MRI evaluation of meniscal tears repaired with bioabsorbable arrows. Scand J Surg 96(3):252–255
Weinand C, Peretti GM, Adams SB Jr, Bonassar LJ, Randolph MA, Gill TJ (2006) An allogenic cell-based implant for meniscal lesions. Am J Sports Med 34(11):1779–1789
Weinand C, Peretti GM, Adams SB Jr, Randolph MA, Savvidis E, Gill TJ (2006) Healing potential of transplanted allogeneic chondrocytes of three different sources in lesions of the avascular zone of the meniscus: a pilot study. Arch Orthop Trauma Surg 126(9):599–605
Acknowledgments
This work was done at the Stem Cell Research Institute, directed by Professor Giulio Cossu. The authors gratefully acknowledge Corrado Sosio, MD for his help in sample implant and harvest; Mr. Paolo Stortini for his precious help in histological analysis. A special thank is given to the Spaccio Agricolo Agripig for their assistance in animal management.
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Scotti, C., Pozzi, A., Mangiavini, L. et al. Healing of meniscal tissue by cellular fibrin glue: an in vivo study. Knee Surg Sports Traumatol Arthrosc 17, 645–651 (2009). https://doi.org/10.1007/s00167-009-0745-9
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DOI: https://doi.org/10.1007/s00167-009-0745-9