Abstract
Polylactic acid polymers have been used extensively as biomaterials and have shown promising properties for cartilage tissue engineering. Numerous scaffold materials exist and the optimal scaffold needs to be identified. We have tried to assess the possibilities for cartilage repair by the use of two different scaffold techniques; autologous chondrocytes in a fibrin hydrogel and a novel MPEG-PLGA scaffold, where autologous chondrocytes are immobilized within the MPEG-PLGA scaffold by a fibrin hydrogel. Twenty adult goats were used for the study. A 6 mm circular full-thickness cartilage defect was created in both medial femoral condyles. The defects were randomized to the following four treatment groups. (1) Empty defect (control). (2) Subchondral drilling (control). (3) Fibrin hydrogel with autologous chondrocytes. (4) Fibrin hydrogel/chondrocyte solution in a MPEG-PLGA porous scaffold. Animals were followed for 4 month. Eight defects in each treatment group completed the study. ICRS macroscopic scoring (0–12). Indentation test was performed to assess stiffness of repair tissue. Histological analyses was performed using O’Driscoll and Pineda cartilage scores as well as percentage tissue filling of the defects. The MPEG-PLGA/chondrocytes scaffold was the superior treatment modality based on the macroscopic surface score, histological scores and defect filling. The mechanical test demonstrated no difference between treatment groups. The MPEG-PLGA/chondrocyte composite demonstrated significantly better cartilage repair response than empty defects, osteochondral drilling and fibrin hydrogel with chondrocytes. The novel MPEG-PLGA scaffold in combination with chondrocytes need further studies with respect to longer follow-up times.
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References
Bentley G, Biant LC, Carrington RW, Akmal M, Goldberg A, Williams AM, Skinner JA, Pringle J (2003) A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br 85:223–230
Breinan HA, Minas T, Hsu HP, Nehrer S, Sledge CB, Spector M (1997) Effect of cultured autologous chondrocytes on repair of chondral defects in a canine model. J Bone Joint Surg Am 79:1439–1451
Dorotka R, Windberger U, Macfelda K, Bindreiter U, Toma C, Nehrer S (2005) Repair of articular cartilage defects treated by microfracture and a three-dimensional collagen matrix. Biomaterials 26:3617–3629
Fortier LA, Mohammed HO, Lust G, Nixon AJ (2002) Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Joint Surg Br 84:276–288
Gigante A, Bevilacqua C, Ricevuto A, Mattioli-Belmonte M, Greco F (2007) Membrane-seeded autologous chondrocytes: cell viability and characterization at surgery. Knee Surg Sports Traumatol Arthrosc 15:88–92
Hendrickson DA, Nixon AJ, Grande DA, Todhunter RJ, Minor RM, Erb H, Lust G (1994) Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects. J Orthop Res 12:485–497
Hoemann CD, Sun J, Legare A, McKee MD, Buschmann MD (2005) Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthritis Cartil 13:318–329
Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartil 10:432–463
Kang SW, Jeon O, Kim BS (2005) Poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for cartilage tissue engineering. Tissue Eng 11:438–447
Kang SW, Yoon JR, Lee JS, Kim HJ, Lim HW, Lim HC, Park JH, Kim BS (2006) The use of poly (lactic-co-glycolic acid) microspheres as injectable cell carriers for cartilage regeneration in rabbit knees. J Biomater Sci Polym Ed 17:925–939
Lee CR, Grodzinsky AJ, Hsu HP, Spector M (2003) Effects of a cultured autologous chondrocyte-seeded type II collagen scaffold on the healing of a chondral defect in a canine model. J Orthop Res 21:272–281
Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Sacchetti GL, Stefani G, Zanasi S (2005) Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res 435:96–105
Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I (2002) Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg Sports Traumatol Arthrosc 10:154–159
Marlovits S, Zeller P, Singer P, Resinger C, Vecsei V (2006) Cartilage repair: generations of autologous chondrocyte transplantation. Eur J Radiol 57:24–31
Niederauer GG, Slivka MA, Leatherbury NC, Korvick DL, Harroff HH, Ehler WC, Dunn CJ, Kieswetter K (2000) Evaluation of multiphase implants for repair of focal osteochondral defects in goats. Biomaterials 21:2561–2574
O’Driscoll SW, Marx RG, Beaton DE, Miura Y, Gallay SH, Fitzsimmons JS (2001) Validation of a simple histological–histochemical cartilage scoring system. Tissue Eng 7:313–320
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 12:1151–1168
Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A (2000) Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop 374:212–234
Pineda S, Pollack A, Stevenson S, Goldberg V, Caplan A (1992) A semiquantitative scale for histologic grading of articular cartilage repair. Acta Anat (Basel) 143:335–340
Pulliainen O, Vasara AI, Hyttinen MM, Tiitu V, Valonen P, Kellomaki M, Jurvelin JS, Peterson L, Lindahl A, Kiviranta I, Lammi MJ (2007) Poly-l-d-lactic acid scaffold in the repair of porcine knee cartilage lesions. Tissue Eng 13:1347–1355
Rudert M, Wilms U, Hoberg M, Wirth CJ (2005) Cell-based treatment of osteochondral defects in the rabbit knee with natural and synthetic matrices: cellular seeding determines the outcome. Arch Orthop Trauma Surg 125:598–608
Solchaga LA, Temenoff JS, Gao J, Mikos AG, Caplan AI, Goldberg VM (2005) Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds. Osteoarthritis Cartil 13:297–309
Steadman JR, Rodkey WG, Rodrigo JJ (2001) Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop 391:362–369
Uematsu K, Hattori K, Ishimoto Y, Yamauchi J, Habata T, Takakura Y, Ohgushi H, Fukuchi T, Sato M (2005) Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold. Biomaterials 26:4273–4279
van Susante JL, Buma P, Homminga GN, van den Berg WB, Veth RP (1998) Chondrocyte-seeded hydroxyapatite for repair of large articular cartilage defects. A pilot study in the goat. Biomaterials 19:2367–2374
van Susante JL, Buma P, Schuman L, Homminga GN, van den Berg WB, Veth RP (1999) Resurfacing potential of heterologous chondrocytes suspended in fibrin glue in large full-thickness defects of femoral articular cartilage: an experimental study in the goat. Biomaterials 20:1167–1175
Vasara AI, Hyttinen MM, Lammi MJ, Lammi PE, Langsjo TK, Lindahl A, Peterson L, Kellomaki M, Konttinen YT, Helminen HJ, Kiviranta I (2004) Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats. Calcif Tissue Int 74:107–114
Wakitani S, Goto T, Young RG, Mansour JM, Goldberg VM, Caplan AI (1998) Repair of large full-thickness articular cartilage defects with allograft articular chondrocytes embedded in a collagen gel. Tissue Eng 4:429–444
Yan H, Yu C (2007) Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy 23:178–187
Acknowledgments
The present study was supported by The Danish Reumatism Association, The Obel Foundation, Denmark. The Orthopedic Research Foundation at Aalborg Hospital, Denmark and Interface Biotech, Denmark.
Conflict of interest statement
Allan Larsen and Martin Lind have received funds as scientific consultants for Interface Biotech. Interface Biotech did not collect data, interpret data or were involved in the writing of the manuscript.
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Lind, M., Larsen, A., Clausen, C. et al. Cartilage repair with chondrocytes in fibrin hydrogel and MPEG polylactide scaffold: an in vivo study in goats. Knee Surg Sports Traumatol Arthr 16, 690–698 (2008). https://doi.org/10.1007/s00167-008-0522-1
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DOI: https://doi.org/10.1007/s00167-008-0522-1