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Published in: Journal of Orthopaedic Surgery and Research 1/2012

Open Access 01-12-2012 | Research article

An ovine in vitro model for chondrocyte-based scaffold-assisted cartilage grafts

Authors: Michaela Endres, Katja Neumann, Bei Zhou, Undine Freymann, David Pretzel, Marcus Stoffel, Raimund W Kinne, Christian Kaps

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2012

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Abstract

Background

Scaffold-assisted autologous chondrocyte implantation is an effective clinical procedure for cartilage repair. From the regulatory point of view, the ovine model is one of the suggested large animal models for pre-clinical studies. The aim of our study was to evaluate the in vitro re-differentiation capacity of expanded ovine chondrocytes in biomechanically characterized polyglycolic acid (PGA)/fibrin biomaterials for scaffold-assisted cartilage repair.

Methods

Ovine chondrocytes harvested from adult articular cartilage were expanded in monolayer and re-assembled three-dimensionally in PGA-fibrin scaffolds. De- and re-differentiation of ovine chondrocytes in PGA-fibrin scaffolds was assessed by histological and immuno-histochemical staining as well as by real-time gene expression analysis of typical cartilage marker molecules and the matrix-remodelling enzymes matrix metalloproteinases (MMP) -1, -2 and −13 as well as their inhibitors. PGA scaffolds characteristics including degradation and stiffness were analysed by electron microscopy and biomechanical testing.

Results

Histological, immuno-histochemical and gene expression analysis showed that dedifferentiated chondrocytes re-differentiate in PGA-fibrin scaffolds and form a cartilaginous matrix. Re-differentiation was accompanied by the induction of type II collagen and aggrecan, while MMP expression decreased in prolonged tissue culture. Electron microscopy and biomechanical tests revealed that the non-woven PGA scaffold shows a textile structure with high tensile strength of 3.6 N/mm2 and a stiffness of up to 0.44 N/mm2, when combined with gel-like fibrin.

Conclusion

These data suggest that PGA-fibrin is suited as a mechanically stable support structure for scaffold-assisted chondrocyte grafts, initiating chondrogenic re-differentiation of expanded chondrocytes.
Appendix
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Literature
1.
go back to reference Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling GG: Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997, 13: 456-460. 10.1016/S0749-8063(97)90124-9.CrossRefPubMed Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling GG: Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997, 13: 456-460. 10.1016/S0749-8063(97)90124-9.CrossRefPubMed
2.
go back to reference Hjelle K, Solheim E, Strand T, Muri R, Brittberg M: Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy. 2002, 18: 730-734. 10.1053/jars.2002.32839.CrossRefPubMed Hjelle K, Solheim E, Strand T, Muri R, Brittberg M: Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy. 2002, 18: 730-734. 10.1053/jars.2002.32839.CrossRefPubMed
3.
go back to reference Widuchowski W, Widuchowski J, Trzaska T: Articular cartilage defects: study of 25,124 knee arthroscopies. Knee. 2007, 14: 177-182. 10.1016/j.knee.2007.02.001.CrossRefPubMed Widuchowski W, Widuchowski J, Trzaska T: Articular cartilage defects: study of 25,124 knee arthroscopies. Knee. 2007, 14: 177-182. 10.1016/j.knee.2007.02.001.CrossRefPubMed
4.
go back to reference Aroen A, Loken S, Heir S, Alvik E, Ekeland A, Granlund OG, Engebretsen L: Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med. 2004, 32: 211-215. 10.1177/0363546503259345.CrossRefPubMed Aroen A, Loken S, Heir S, Alvik E, Ekeland A, Granlund OG, Engebretsen L: Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med. 2004, 32: 211-215. 10.1177/0363546503259345.CrossRefPubMed
5.
go back to reference Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994, 331: 889-895. 10.1056/NEJM199410063311401.CrossRefPubMed Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994, 331: 889-895. 10.1056/NEJM199410063311401.CrossRefPubMed
6.
go back to reference Hubbard MJ: Articular debridement versus washout for degeneration of the medial femoral condyle. A five-year study. J Bone Joint Surg Br. 1996, 78: 217-219.PubMed Hubbard MJ: Articular debridement versus washout for degeneration of the medial femoral condyle. A five-year study. J Bone Joint Surg Br. 1996, 78: 217-219.PubMed
7.
go back to reference Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R: Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. J Bone Joint Surg Am. 2003, 85 (A): 185-192.PubMed Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R: Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. J Bone Joint Surg Am. 2003, 85 (A): 185-192.PubMed
8.
go back to reference Magnussen RA, Dunn WR, Carey JL, Spindler KP: Treatment of focal articular cartilage defects in the knee: a systematic review. Clin Orthop Relat Res. 2008, 466: 952-962. 10.1007/s11999-007-0097-z.PubMedCentralCrossRefPubMed Magnussen RA, Dunn WR, Carey JL, Spindler KP: Treatment of focal articular cartilage defects in the knee: a systematic review. Clin Orthop Relat Res. 2008, 466: 952-962. 10.1007/s11999-007-0097-z.PubMedCentralCrossRefPubMed
9.
go back to reference Steadman JR, Rodkey WG, Rodrigo JJ: Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res. 2001, 391: S362-S369.CrossRefPubMed Steadman JR, Rodkey WG, Rodrigo JJ: Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res. 2001, 391: S362-S369.CrossRefPubMed
10.
go back to reference Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O: A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007, 89: 2105-2112. 10.2106/JBJS.G.00003.CrossRefPubMed Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O: A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007, 89: 2105-2112. 10.2106/JBJS.G.00003.CrossRefPubMed
11.
go back to reference Moseley JB, Anderson AF, Browne JE, Mandelbaum BR, Micheli LJ, Fu F, Erggelet C: Long-term durability of autologous chondrocyte implantation: a multicenter, observational study in US patients. Am J Sports Med. 2010, 38: 238-246. 10.1177/0363546509348000.CrossRefPubMed Moseley JB, Anderson AF, Browne JE, Mandelbaum BR, Micheli LJ, Fu F, Erggelet C: Long-term durability of autologous chondrocyte implantation: a multicenter, observational study in US patients. Am J Sports Med. 2010, 38: 238-246. 10.1177/0363546509348000.CrossRefPubMed
12.
go back to reference Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A: Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000, 374: 212-234.CrossRefPubMed Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A: Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000, 374: 212-234.CrossRefPubMed
13.
go back to reference Bentley G, Biant LC, Carrington RW, Akmal M, Goldberg A, Williams AM, Skinner JA, Pringle J: A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br. 2003, 85: 223-230. 10.1302/0301-620X.85B2.13543.CrossRefPubMed Bentley G, Biant LC, Carrington RW, Akmal M, Goldberg A, Williams AM, Skinner JA, Pringle J: A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br. 2003, 85: 223-230. 10.1302/0301-620X.85B2.13543.CrossRefPubMed
14.
go back to reference Wasiak J, Clar C, Villanueva E: Autologous cartilage implantation for full thickness articular cartilage defects of the knee. Cochrane Database Syst Rev. 2006, 3: CD003323-PubMed Wasiak J, Clar C, Villanueva E: Autologous cartilage implantation for full thickness articular cartilage defects of the knee. Cochrane Database Syst Rev. 2006, 3: CD003323-PubMed
15.
go back to reference Brittberg M: Autologous chondrocyte implantation–technique and long-term follow-up. Injury. 2008, 39 (Suppl 1): S40-S49.CrossRefPubMed Brittberg M: Autologous chondrocyte implantation–technique and long-term follow-up. Injury. 2008, 39 (Suppl 1): S40-S49.CrossRefPubMed
16.
go back to reference Minas T: Autologous chondrocyte implantation for focal chondral defects of the knee. Clin Orthop Relat Res. 2001, 391: S349-S361.CrossRefPubMed Minas T: Autologous chondrocyte implantation for focal chondral defects of the knee. Clin Orthop Relat Res. 2001, 391: S349-S361.CrossRefPubMed
17.
go back to reference Gooding CR, Bartlett W, Bentley G, Skinner JA, Carrington R, Flanagan A: A prospective, randomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I/III collagen covered. Knee. 2006, 13: 203-210. 10.1016/j.knee.2006.02.011.CrossRefPubMed Gooding CR, Bartlett W, Bentley G, Skinner JA, Carrington R, Flanagan A: A prospective, randomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I/III collagen covered. Knee. 2006, 13: 203-210. 10.1016/j.knee.2006.02.011.CrossRefPubMed
18.
go back to reference Kon E, Di Martino A, Filardo G, Tetta C, Busacca M, Iacono F, Delcogliano M, Albisinni U, Marcacci M: Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur J Radiol. 2011, 79: 382-388. 10.1016/j.ejrad.2010.04.002.CrossRefPubMed Kon E, Di Martino A, Filardo G, Tetta C, Busacca M, Iacono F, Delcogliano M, Albisinni U, Marcacci M: Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur J Radiol. 2011, 79: 382-388. 10.1016/j.ejrad.2010.04.002.CrossRefPubMed
19.
go back to reference Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Scchaetti GL, Stefani G, Zanasi S: Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Rel Res. 2005, 435: 96-105.CrossRef Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Scchaetti GL, Stefani G, Zanasi S: Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Rel Res. 2005, 435: 96-105.CrossRef
20.
go back to reference Behrens P, Bitter T, Kurz B, Russlies M: Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)–5-year follow-up. Knee. 2006, 13: 194-202. 10.1016/j.knee.2006.02.012.CrossRefPubMed Behrens P, Bitter T, Kurz B, Russlies M: Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)–5-year follow-up. Knee. 2006, 13: 194-202. 10.1016/j.knee.2006.02.012.CrossRefPubMed
21.
go back to reference Niemeyer P, Lenz P, Kreuz PC, Salzmann GM, Sudkamp NP, Schmal H, Steinwachs M: Chondrocyte-seeded type I/III collagen membrane for autologous chondrocyte transplantation: prospective 2-year results in patients with cartilage defects of the knee joint. Arthroscopy. 2010, 26: 1074-1082. 10.1016/j.arthro.2009.12.028.CrossRefPubMed Niemeyer P, Lenz P, Kreuz PC, Salzmann GM, Sudkamp NP, Schmal H, Steinwachs M: Chondrocyte-seeded type I/III collagen membrane for autologous chondrocyte transplantation: prospective 2-year results in patients with cartilage defects of the knee joint. Arthroscopy. 2010, 26: 1074-1082. 10.1016/j.arthro.2009.12.028.CrossRefPubMed
22.
go back to reference Kreuz PC, Muller S, Ossendorf C, Kaps C, Erggelet C: Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res Ther. 2009, 11: R33-10.1186/ar2638.PubMedCentralCrossRefPubMed Kreuz PC, Muller S, Ossendorf C, Kaps C, Erggelet C: Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res Ther. 2009, 11: R33-10.1186/ar2638.PubMedCentralCrossRefPubMed
23.
go back to reference Levine DW, Mondano L, Halpin M: FDA regulatory pathways for knee cartilage repair products. Sports Med Arthrosc. 2008, 16: 202-207. 10.1097/JSA.0b013e31818cdb97.CrossRefPubMed Levine DW, Mondano L, Halpin M: FDA regulatory pathways for knee cartilage repair products. Sports Med Arthrosc. 2008, 16: 202-207. 10.1097/JSA.0b013e31818cdb97.CrossRefPubMed
25.
26.
go back to reference EMA: Reflection paper on in-vitro cultured chondrocyte containing products for cartilage repair of the knee. 2010, EMA/CAT/CPWP/568181/2009, www.ema.europa.eu EMA: Reflection paper on in-vitro cultured chondrocyte containing products for cartilage repair of the knee. 2010, EMA/CAT/CPWP/568181/2009, www.​ema.​europa.​eu
27.
go back to reference Stoffel M, Weichert D, Müller-Rath R: A constitutive model for articular cartilage replacement materials. Biomaterialien. 2009, 10: 79-86. Stoffel M, Weichert D, Müller-Rath R: A constitutive model for articular cartilage replacement materials. Biomaterialien. 2009, 10: 79-86.
28.
go back to reference Benya PD, Shaffer JD: Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. 1982, 30: 215-224. 10.1016/0092-8674(82)90027-7.CrossRefPubMed Benya PD, Shaffer JD: Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. 1982, 30: 215-224. 10.1016/0092-8674(82)90027-7.CrossRefPubMed
29.
go back to reference Kolettas E, Buluwela L, Bayliss MT, Muir HI: Expression of cartilage-specific molecules is retained on long-term culture of human articular chondrocytes. J Cell Sci. 1995, 108: 1991-1999.PubMed Kolettas E, Buluwela L, Bayliss MT, Muir HI: Expression of cartilage-specific molecules is retained on long-term culture of human articular chondrocytes. J Cell Sci. 1995, 108: 1991-1999.PubMed
30.
go back to reference Kaps C, Frauenschuh S, Endres M, Ringe J, Haisch A, Lauber J, Buer J, Krenn V, Haupl T, Burmester GR, Sittinger M: Gene expression profiling of human articular cartilage grafts generated by tissue engineering. Biomaterials. 2006, 27: 3617-3630.PubMed Kaps C, Frauenschuh S, Endres M, Ringe J, Haisch A, Lauber J, Buer J, Krenn V, Haupl T, Burmester GR, Sittinger M: Gene expression profiling of human articular cartilage grafts generated by tissue engineering. Biomaterials. 2006, 27: 3617-3630.PubMed
31.
go back to reference Rotter N, Aigner J, Naumann A, Planck H, Hammer C, Burmester G, Sittinger M: Cartilage reconstruction in head and neck surgery: comparison of resorbable polymer scaffolds for tissue engineering of human septal cartilage. J Biomed Mater Res. 1998, 42: 347-356. 10.1002/(SICI)1097-4636(19981205)42:3<347::AID-JBM2>3.0.CO;2-J.CrossRefPubMed Rotter N, Aigner J, Naumann A, Planck H, Hammer C, Burmester G, Sittinger M: Cartilage reconstruction in head and neck surgery: comparison of resorbable polymer scaffolds for tissue engineering of human septal cartilage. J Biomed Mater Res. 1998, 42: 347-356. 10.1002/(SICI)1097-4636(19981205)42:3<347::AID-JBM2>3.0.CO;2-J.CrossRefPubMed
32.
go back to reference Perka C, Sittinger M, Schultz O, Spitzer RS, Schlenzka D, Burmester GR: Tissue engineered cartilage repair using cryopreserved and noncryopreserved chondrocytes. Clin Orthop Relat Res. 2000, 378: 245-254.CrossRefPubMed Perka C, Sittinger M, Schultz O, Spitzer RS, Schlenzka D, Burmester GR: Tissue engineered cartilage repair using cryopreserved and noncryopreserved chondrocytes. Clin Orthop Relat Res. 2000, 378: 245-254.CrossRefPubMed
33.
go back to reference Barnewitz D, Endres M, Kruger I, Becker A, Zimmermann J, Wilke I, Ringe J, Sittinger M, Kaps C: Treatment of articular cartilage defects in horses with polymer-based cartilage tissue engineering grafts. Biomaterials. 2006, 27: 2882-2889. 10.1016/j.biomaterials.2006.01.008.CrossRefPubMed Barnewitz D, Endres M, Kruger I, Becker A, Zimmermann J, Wilke I, Ringe J, Sittinger M, Kaps C: Treatment of articular cartilage defects in horses with polymer-based cartilage tissue engineering grafts. Biomaterials. 2006, 27: 2882-2889. 10.1016/j.biomaterials.2006.01.008.CrossRefPubMed
34.
go back to reference Endres M, Neumann K, Schroder SE, Vetterlein S, Morawietz L, Ringe J, Sittinger M, Kaps C: Human polymer-based cartilage grafts for the regeneration of articular cartilage defects. Tissue Cell. 2007, 39: 293-301. 10.1016/j.tice.2007.05.002.CrossRefPubMed Endres M, Neumann K, Schroder SE, Vetterlein S, Morawietz L, Ringe J, Sittinger M, Kaps C: Human polymer-based cartilage grafts for the regeneration of articular cartilage defects. Tissue Cell. 2007, 39: 293-301. 10.1016/j.tice.2007.05.002.CrossRefPubMed
35.
go back to reference Huch K, Stove J, Puhl W, Gunther KP: Review and comparison of culture-techniques for articular chondrocytes. Z Orthop Ihre Grenzgeb. 2002, 140: 145-152. 10.1055/s-2002-31532.CrossRefPubMed Huch K, Stove J, Puhl W, Gunther KP: Review and comparison of culture-techniques for articular chondrocytes. Z Orthop Ihre Grenzgeb. 2002, 140: 145-152. 10.1055/s-2002-31532.CrossRefPubMed
36.
go back to reference Behrens P, Bosch U, Bruns J, Erggelet C, Esenwein SA, Gaissmaier C, Krackhardt T, Lohnert J, Marlovits S, Meenen NM, Mollenhauer J: Indications and implementation of recommendations of the working group "Tissue Regeneration and Tissue Substitutes" for autologous chondrocyte transplantation (ACT). Z Orthop Ihre Grenzgeb. 2004, 142: 529-539. 10.1055/s-2004-832353.CrossRefPubMed Behrens P, Bosch U, Bruns J, Erggelet C, Esenwein SA, Gaissmaier C, Krackhardt T, Lohnert J, Marlovits S, Meenen NM, Mollenhauer J: Indications and implementation of recommendations of the working group "Tissue Regeneration and Tissue Substitutes" for autologous chondrocyte transplantation (ACT). Z Orthop Ihre Grenzgeb. 2004, 142: 529-539. 10.1055/s-2004-832353.CrossRefPubMed
37.
go back to reference Dell'Accio F, De Bari C, Luyten FP: Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo. Arthritis Rheum. 2001, 44: 1608-1619. 10.1002/1529-0131(200107)44:7<1608::AID-ART284>3.0.CO;2-T.CrossRefPubMed Dell'Accio F, De Bari C, Luyten FP: Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo. Arthritis Rheum. 2001, 44: 1608-1619. 10.1002/1529-0131(200107)44:7<1608::AID-ART284>3.0.CO;2-T.CrossRefPubMed
38.
go back to reference Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G: Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem. 1996, 271: 17124-17131. 10.1074/jbc.271.29.17124.CrossRefPubMed Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G: Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem. 1996, 271: 17124-17131. 10.1074/jbc.271.29.17124.CrossRefPubMed
39.
go back to reference Tetlow LC, Adlam DJ, Woolley DE: Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 2001, 44: 585-594. 10.1002/1529-0131(200103)44:3<585::AID-ANR107>3.0.CO;2-C.CrossRefPubMed Tetlow LC, Adlam DJ, Woolley DE: Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 2001, 44: 585-594. 10.1002/1529-0131(200103)44:3<585::AID-ANR107>3.0.CO;2-C.CrossRefPubMed
40.
go back to reference Stickens D, Behonick DJ, Ortega N, Heyer B, Hartenstein B, Yu Y, Fosang AJ, Schorpp-Kistner M, Angel P, Werb Z: Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development. 2004, 131: 5883-5895. 10.1242/dev.01461.PubMedCentralCrossRefPubMed Stickens D, Behonick DJ, Ortega N, Heyer B, Hartenstein B, Yu Y, Fosang AJ, Schorpp-Kistner M, Angel P, Werb Z: Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development. 2004, 131: 5883-5895. 10.1242/dev.01461.PubMedCentralCrossRefPubMed
41.
go back to reference Takaishi H, Kimura T, Dalal S, Okada Y, D'Armiento J: Joint diseases and matrix metalloproteinases: a role for MMP-13. Curr Pharm Biotechnol. 2008, 9: 47-54. 10.2174/138920108783497659.CrossRefPubMed Takaishi H, Kimura T, Dalal S, Okada Y, D'Armiento J: Joint diseases and matrix metalloproteinases: a role for MMP-13. Curr Pharm Biotechnol. 2008, 9: 47-54. 10.2174/138920108783497659.CrossRefPubMed
42.
go back to reference Borzi RM, Olivotto E, Pagani S, Vitellozzi R, Neri S, Battistelli M, Falcieri E, Facchini A, Flamigni F, Penzo M, Platano D: Matrix metalloproteinase 13 loss associated with impaired extracellular matrix remodeling disrupts chondrocyte differentiation by concerted effects on multiple regulatory factors. Arthritis Rheum. 2010, 62: 2370-2381. 10.1002/art.27512.PubMedCentralCrossRefPubMed Borzi RM, Olivotto E, Pagani S, Vitellozzi R, Neri S, Battistelli M, Falcieri E, Facchini A, Flamigni F, Penzo M, Platano D: Matrix metalloproteinase 13 loss associated with impaired extracellular matrix remodeling disrupts chondrocyte differentiation by concerted effects on multiple regulatory factors. Arthritis Rheum. 2010, 62: 2370-2381. 10.1002/art.27512.PubMedCentralCrossRefPubMed
43.
go back to reference Sahebjam S, Khokha R, Mort JS: Increased collagen and aggrecan degradation with age in the joints of Timp3(−/−) mice. Arthritis Rheum. 2007, 56: 905-909. 10.1002/art.22427.CrossRefPubMed Sahebjam S, Khokha R, Mort JS: Increased collagen and aggrecan degradation with age in the joints of Timp3(−/−) mice. Arthritis Rheum. 2007, 56: 905-909. 10.1002/art.22427.CrossRefPubMed
44.
45.
go back to reference Bau B, Gebhard PM, Haag J, Knorr T, Bartnik E, Aigner T: Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. Arthritis Rheum. 2002, 46: 2648-2657. 10.1002/art.10531.CrossRefPubMed Bau B, Gebhard PM, Haag J, Knorr T, Bartnik E, Aigner T: Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. Arthritis Rheum. 2002, 46: 2648-2657. 10.1002/art.10531.CrossRefPubMed
46.
go back to reference Duda GN, Haisch A, Endres M, Gebert C, Schroeder D, Hoffmann JE, Sittinger M: Mechanical quality of tissue engineered cartilage: results after 6 and 12 weeks in vivo. J Biomed Mater Res. 2000, 53: 673-677. 10.1002/1097-4636(2000)53:6<673::AID-JBM9>3.0.CO;2-V.CrossRefPubMed Duda GN, Haisch A, Endres M, Gebert C, Schroeder D, Hoffmann JE, Sittinger M: Mechanical quality of tissue engineered cartilage: results after 6 and 12 weeks in vivo. J Biomed Mater Res. 2000, 53: 673-677. 10.1002/1097-4636(2000)53:6<673::AID-JBM9>3.0.CO;2-V.CrossRefPubMed
47.
go back to reference Grad S, Kupcsik L, Gorna K, Gogolewski S, Alini M: The use of biodegradable polyurethane scaffolds for cartilage tissue engineering: potential and limitations. Biomaterials. 2003, 24: 5163-5171. 10.1016/S0142-9612(03)00462-9.CrossRefPubMed Grad S, Kupcsik L, Gorna K, Gogolewski S, Alini M: The use of biodegradable polyurethane scaffolds for cartilage tissue engineering: potential and limitations. Biomaterials. 2003, 24: 5163-5171. 10.1016/S0142-9612(03)00462-9.CrossRefPubMed
48.
go back to reference Nehrer S, Spector M, Minas T: Histologic analysis of tissue after failed cartilage repair procedures. Clin Orthop Relat Res. 1999, 365: 149-162.CrossRefPubMed Nehrer S, Spector M, Minas T: Histologic analysis of tissue after failed cartilage repair procedures. Clin Orthop Relat Res. 1999, 365: 149-162.CrossRefPubMed
49.
go back to reference Nehrer S, Domayer S, Dorotka R, Schatz K, Bindreiter U, Kotz R: Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair. Eur J Radiol. 2006, 57: 3-8. 10.1016/j.ejrad.2005.08.005.CrossRefPubMed Nehrer S, Domayer S, Dorotka R, Schatz K, Bindreiter U, Kotz R: Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair. Eur J Radiol. 2006, 57: 3-8. 10.1016/j.ejrad.2005.08.005.CrossRefPubMed
50.
go back to reference Knecht S, Erggelet C, Endres M, Sittinger M, Kaps C, Stussi E: Mechanical testing of fixation techniques for scaffold-based tissue-engineered grafts. J Biomed Mater Res B Appl Biomater. 2007, 83B: 50-57. 10.1002/jbm.b.30765.CrossRef Knecht S, Erggelet C, Endres M, Sittinger M, Kaps C, Stussi E: Mechanical testing of fixation techniques for scaffold-based tissue-engineered grafts. J Biomed Mater Res B Appl Biomater. 2007, 83B: 50-57. 10.1002/jbm.b.30765.CrossRef
51.
go back to reference Drobnic M, Radosavljevic D, Ravnik D, Pavlovcic V, Hribernik M: Comparison of four techniques for the fixation of a collagen scaffold in the human cadaveric knee. Osteoarthritis Cartilage. 2006, 14: 337-344. 10.1016/j.joca.2005.11.007.CrossRefPubMed Drobnic M, Radosavljevic D, Ravnik D, Pavlovcic V, Hribernik M: Comparison of four techniques for the fixation of a collagen scaffold in the human cadaveric knee. Osteoarthritis Cartilage. 2006, 14: 337-344. 10.1016/j.joca.2005.11.007.CrossRefPubMed
Metadata
Title
An ovine in vitro model for chondrocyte-based scaffold-assisted cartilage grafts
Authors
Michaela Endres
Katja Neumann
Bei Zhou
Undine Freymann
David Pretzel
Marcus Stoffel
Raimund W Kinne
Christian Kaps
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2012
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/1749-799X-7-37

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