Skip to main content
Top
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 7/2008

01-07-2008 | Experimental Study

Cartilage repair with chondrocytes in fibrin hydrogel and MPEG polylactide scaffold: an in vivo study in goats

Authors: Martin Lind, Allan Larsen, Christian Clausen, Kurt Osther, Hanne Everland

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 7/2008

Login to get access

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.
Literature
1.
go back to reference 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 85:223–230PubMedCrossRef 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 85:223–230PubMedCrossRef
2.
go back to reference 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 79:1439–1451PubMed 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 79:1439–1451PubMed
3.
go back to reference 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 26:3617–3629PubMedCrossRef 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 26:3617–3629PubMedCrossRef
4.
go back to reference 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 84:276–288PubMedCrossRef 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 84:276–288PubMedCrossRef
5.
go back to reference 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 15:88–92PubMedCrossRef 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 15:88–92PubMedCrossRef
6.
go back to reference 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 12:485–497PubMedCrossRef 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 12:485–497PubMedCrossRef
7.
go back to reference 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 13:318–329CrossRef 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 13:318–329CrossRef
8.
go back to reference Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartil 10:432–463CrossRef Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartil 10:432–463CrossRef
9.
go back to reference Kang SW, Jeon O, Kim BS (2005) Poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for cartilage tissue engineering. Tissue Eng 11:438–447PubMedCrossRef Kang SW, Jeon O, Kim BS (2005) Poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for cartilage tissue engineering. Tissue Eng 11:438–447PubMedCrossRef
10.
go back to reference 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 17:925–939PubMedCrossRef 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 17:925–939PubMedCrossRef
11.
go back to reference 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 21:272–281PubMedCrossRef 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 21:272–281PubMedCrossRef
12.
go back to reference 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 435:96–105PubMedCrossRef 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 435:96–105PubMedCrossRef
13.
go back to reference Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I (2002) Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg Sports Traumatol Arthrosc 10:154–159PubMedCrossRef Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I (2002) Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg Sports Traumatol Arthrosc 10:154–159PubMedCrossRef
14.
go back to reference Marlovits S, Zeller P, Singer P, Resinger C, Vecsei V (2006) Cartilage repair: generations of autologous chondrocyte transplantation. Eur J Radiol 57:24–31PubMedCrossRef Marlovits S, Zeller P, Singer P, Resinger C, Vecsei V (2006) Cartilage repair: generations of autologous chondrocyte transplantation. Eur J Radiol 57:24–31PubMedCrossRef
15.
go back to reference 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 21:2561–2574PubMedCrossRef 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 21:2561–2574PubMedCrossRef
16.
go back to reference 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 7:313–320PubMedCrossRef 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 7:313–320PubMedCrossRef
17.
go back to reference 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 12:1151–1168PubMedCrossRef 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 12:1151–1168PubMedCrossRef
18.
go back to reference 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 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
19.
go back to reference 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 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
20.
go back to reference 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 13:1347–1355PubMedCrossRef 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 13:1347–1355PubMedCrossRef
21.
go back to reference 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 125:598–608PubMedCrossRef 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 125:598–608PubMedCrossRef
22.
go back to reference 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 13:297–309CrossRef 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 13:297–309CrossRef
23.
go back to reference Steadman JR, Rodkey WG, Rodrigo JJ (2001) Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop 391:362–369CrossRef Steadman JR, Rodkey WG, Rodrigo JJ (2001) Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop 391:362–369CrossRef
24.
go back to reference 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 26:4273–4279PubMedCrossRef 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 26:4273–4279PubMedCrossRef
25.
go back to reference 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 19:2367–2374PubMedCrossRef 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 19:2367–2374PubMedCrossRef
26.
go back to reference 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 20:1167–1175PubMedCrossRef 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 20:1167–1175PubMedCrossRef
27.
go back to reference 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 74:107–114PubMedCrossRef 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 74:107–114PubMedCrossRef
28.
go back to reference 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 4:429–444PubMedCrossRef 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 4:429–444PubMedCrossRef
29.
go back to reference Yan H, Yu C (2007) Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy 23:178–187PubMedCrossRef Yan H, Yu C (2007) Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy 23:178–187PubMedCrossRef
Metadata
Title
Cartilage repair with chondrocytes in fibrin hydrogel and MPEG polylactide scaffold: an in vivo study in goats
Authors
Martin Lind
Allan Larsen
Christian Clausen
Kurt Osther
Hanne Everland
Publication date
01-07-2008
Publisher
Springer-Verlag
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 7/2008
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-008-0522-1

Other articles of this Issue 7/2008

Knee Surgery, Sports Traumatology, Arthroscopy 7/2008 Go to the issue