Skip to main content
Top
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 6/2012

01-06-2012 | Experimental Study

A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies

Authors: Bjørn Borsøe Christensen, Casper Bindzus Foldager, Ole Møller Hansen, Asger Albæk Kristiansen, Dang Quang Svend Le, Agnete Desirée Nielsen, Jens Vinge Nygaard, Cody Erik Bünger, Martin Lind

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 6/2012

Login to get access

Abstract

Purpose

To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide®) scaffold.

Methods

By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water–dioxane–PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT–PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide® scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O’Driscoll score.

Results

In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide® scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide® scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells.

Conclusion

The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide® scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide® scaffold with cells.
Literature
1.
go back to reference Behrens P, Bitter T, Kurz B, Russlies M (2006) Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI): 5-year follow-up. Knee 13:194–202PubMedCrossRef Behrens P, Bitter T, Kurz B, Russlies M (2006) Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI): 5-year follow-up. Knee 13:194–202PubMedCrossRef
2.
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, Nehrer S, Niethard FU, Noth U, Perka C, Richter W, Schafer D, Schneider U, Steinwachs M, Weise K (2004) Indications and implementation of recommendations of the working group “tissue regeneration and tissue substitutes” for autologous chondrocyte transplantation (ACT). Z Orthop Ihre Grenzgeb 142:529–539PubMedCrossRef Behrens P, Bosch U, Bruns J, Erggelet C, Esenwein SA, Gaissmaier C, Krackhardt T, Lohnert J, Marlovits S, Meenen NM, Mollenhauer J, Nehrer S, Niethard FU, Noth U, Perka C, Richter W, Schafer D, Schneider U, Steinwachs M, Weise K (2004) Indications and implementation of recommendations of the working group “tissue regeneration and tissue substitutes” for autologous chondrocyte transplantation (ACT). Z Orthop Ihre Grenzgeb 142:529–539PubMedCrossRef
3.
go back to reference Benthien JP, Behrens P (2010) Autologous matrix-induced chondrogenesis (AMIC). A one-step procedure for retropatellar articular resurfacing. Acta Orthop Belg 76:260–263PubMed Benthien JP, Behrens P (2010) Autologous matrix-induced chondrogenesis (AMIC). A one-step procedure for retropatellar articular resurfacing. Acta Orthop Belg 76:260–263PubMed
4.
go back to reference Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895PubMedCrossRef Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895PubMedCrossRef
5.
go back to reference Buckwalter JA, Mankin HJ (1998) Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 47:487–504PubMed Buckwalter JA, Mankin HJ (1998) Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 47:487–504PubMed
6.
go back to reference Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310:1139–1143PubMedCrossRef Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310:1139–1143PubMedCrossRef
7.
go back to reference Ehlers EM, Fuss M, Rohwedel J, Russlies M, Kuhnel W, Behrens P (1999) Development of a biocomposite to fill out articular cartilage lesions. Light, scanning and transmission electron microscopy of sheep chondrocytes cultured on a collagen I/III sponge. Ann Anat 181:513–518PubMedCrossRef Ehlers EM, Fuss M, Rohwedel J, Russlies M, Kuhnel W, Behrens P (1999) Development of a biocomposite to fill out articular cartilage lesions. Light, scanning and transmission electron microscopy of sheep chondrocytes cultured on a collagen I/III sponge. Ann Anat 181:513–518PubMedCrossRef
8.
go back to reference Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689PubMedCrossRef Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689PubMedCrossRef
9.
go back to reference Haddo O, Mahroof S, Higgs D, David L, Pringle J, Bayliss M, Cannon SR, Briggs TW (2004) The use of chondrogide membrane in autologous chondrocyte implantation. Knee 11:51–55PubMedCrossRef Haddo O, Mahroof S, Higgs D, David L, Pringle J, Bayliss M, Cannon SR, Briggs TW (2004) The use of chondrogide membrane in autologous chondrocyte implantation. Knee 11:51–55PubMedCrossRef
10.
go back to reference Hall FM, Wyshak G (1980) Thickness of articular cartilage in the normal knee. J Bone Jt Surg Am 62:408–413 Hall FM, Wyshak G (1980) Thickness of articular cartilage in the normal knee. J Bone Jt Surg Am 62:408–413
11.
go back to reference Hattori T, Muller C, Gebhard S, Bauer E, Pausch F, Schlund B, Bosl MR, Hess A, Surmann-Schmitt C, von der Mark H, de Crombrugghe B, von der Mark K (2010) SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification. Development 137:901–911PubMedCrossRef Hattori T, Muller C, Gebhard S, Bauer E, Pausch F, Schlund B, Bosl MR, Hess A, Surmann-Schmitt C, von der Mark H, de Crombrugghe B, von der Mark K (2010) SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification. Development 137:901–911PubMedCrossRef
12.
go back to reference Ho ST, Hutmacher DW, Ekaputra AK, Hitendra D, Hui JH (2010) The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model. Tiss Eng Part A 16:1123–1141CrossRef Ho ST, Hutmacher DW, Ekaputra AK, Hitendra D, Hui JH (2010) The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model. Tiss Eng Part A 16:1123–1141CrossRef
13.
go back to reference Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10:432–463PubMedCrossRef Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10:432–463PubMedCrossRef
14.
go back to reference Kon E, Filardo G, Condello V, Collarile M, Di Martino A, Zorzi C, Marcacci M (2011) Second-generation autologous chondrocyte implantation: results in patients older than 40 years. Am J Sports Med 39:1668–1675PubMedCrossRef Kon E, Filardo G, Condello V, Collarile M, Di Martino A, Zorzi C, Marcacci M (2011) Second-generation autologous chondrocyte implantation: results in patients older than 40 years. Am J Sports Med 39:1668–1675PubMedCrossRef
15.
go back to reference Krishnan SP, Skinner JA, Carrington RW, Flanagan AM, Briggs TW, Bentley G (2006) Collagen-covered autologous chondrocyte implantation for osteochondritis dissecans of the knee: 2–7-year results. J Bone Jt Surg Br 88:203–205CrossRef Krishnan SP, Skinner JA, Carrington RW, Flanagan AM, Briggs TW, Bentley G (2006) Collagen-covered autologous chondrocyte implantation for osteochondritis dissecans of the knee: 2–7-year results. J Bone Jt Surg Br 88:203–205CrossRef
16.
go back to reference Kubo S, Cooper GM, Matsumoto T, Phillippi JA, Corsi KA, Usas A, Li G, Fu FH, Huard J (2009) Blocking vascular endothelial growth factor with soluble Flt-1 improves the chondrogenic potential of mouse skeletal muscle-derived stem cells. Arthritis Rheum 60:155–165PubMedCrossRef Kubo S, Cooper GM, Matsumoto T, Phillippi JA, Corsi KA, Usas A, Li G, Fu FH, Huard J (2009) Blocking vascular endothelial growth factor with soluble Flt-1 improves the chondrogenic potential of mouse skeletal muscle-derived stem cells. Arthritis Rheum 60:155–165PubMedCrossRef
17.
go back to reference Lam CX, Hutmacher DW, Schantz JT, Woodruff MA, Teoh SH (2009) Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo. J Biomed Mater Res A 90:906–919PubMed Lam CX, Hutmacher DW, Schantz JT, Woodruff MA, Teoh SH (2009) Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo. J Biomed Mater Res A 90:906–919PubMed
18.
go back to reference Maehara H, Sotome S, Yoshii T, Torigoe I, Kawasaki Y, Sugata Y, Yuasa M, Hirano M, Mochizuki N, Kikuchi M, Shinomiya K, Okawa A (2010) Repair of large osteochondral defects in rabbits using porous hydroxyapatite/collagen (HAp/Col) and fibroblast growth factor-2 (FGF-2). J Orthop Res 28:677–686PubMed Maehara H, Sotome S, Yoshii T, Torigoe I, Kawasaki Y, Sugata Y, Yuasa M, Hirano M, Mochizuki N, Kikuchi M, Shinomiya K, Okawa A (2010) Repair of large osteochondral defects in rabbits using porous hydroxyapatite/collagen (HAp/Col) and fibroblast growth factor-2 (FGF-2). J Orthop Res 28:677–686PubMed
19.
go back to reference Martinez-Diaz S, Garcia-Giralt N, Lebourg M, Gomez-Tejedor JA, Vila G, Caceres E, Benito P, Pradas MM, Nogues X, Ribelles JL, Monllau JC (2010) In vivo evaluation of 3-D polycaprolactone scaffolds for cartilage repair in rabbits. Am J Sports Med 38:509–519PubMedCrossRef Martinez-Diaz S, Garcia-Giralt N, Lebourg M, Gomez-Tejedor JA, Vila G, Caceres E, Benito P, Pradas MM, Nogues X, Ribelles JL, Monllau JC (2010) In vivo evaluation of 3-D polycaprolactone scaffolds for cartilage repair in rabbits. Am J Sports Med 38:509–519PubMedCrossRef
20.
go back to reference Minas T, Nehrer S (1997) Current concepts in the treatment of articular cartilage defects. Orthopedics 20:525–538PubMed Minas T, Nehrer S (1997) Current concepts in the treatment of articular cartilage defects. Orthopedics 20:525–538PubMed
21.
go back to reference Mrosek EH, Schagemann JC, Chung HW, Fitzsimmons JS, Yaszemski MJ, Mardones RM, O’Driscoll SW, Reinholz GG (2010) Porous tantalum and poly-epsilon-caprolactone biocomposites for osteochondral defect repair: preliminary studies in rabbits. J Orthop Res 28:141–148PubMed Mrosek EH, Schagemann JC, Chung HW, Fitzsimmons JS, Yaszemski MJ, Mardones RM, O’Driscoll SW, Reinholz GG (2010) Porous tantalum and poly-epsilon-caprolactone biocomposites for osteochondral defect repair: preliminary studies in rabbits. J Orthop Res 28:141–148PubMed
22.
go back to reference Ng KW, Hutmacher DW, Schantz JT, Ng CS, Too HP, Lim TC, Phan TT, Teoh SH (2001) Evaluation of ultra-thin poly(epsilon-caprolactone) films for tissue-engineered skin. Tiss Eng 7:441–455CrossRef Ng KW, Hutmacher DW, Schantz JT, Ng CS, Too HP, Lim TC, Phan TT, Teoh SH (2001) Evaluation of ultra-thin poly(epsilon-caprolactone) films for tissue-engineered skin. Tiss Eng 7:441–455CrossRef
23.
go back to reference Niemeyer P, Pestka JM, Kreuz PC, Erggelet C, Schmal H, Suedkamp NP, Steinwachs M (2008) Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. Am J Sports Med 36:2091–2099PubMedCrossRef Niemeyer P, Pestka JM, Kreuz PC, Erggelet C, Schmal H, Suedkamp NP, Steinwachs M (2008) Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. Am J Sports Med 36:2091–2099PubMedCrossRef
24.
go back to reference O’Driscoll SW, Keeley FW, Salter RB (1988) Durability of regenerated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint surfaces under the influence of continuous passive motion. A follow-up report at 1 year. J Bone Jt Surg Am 70:595–606 O’Driscoll SW, Keeley FW, Salter RB (1988) Durability of regenerated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint surfaces under the influence of continuous passive motion. A follow-up report at 1 year. J Bone Jt Surg Am 70:595–606
25.
go back to reference Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP (2004) Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: best keeper–excel-based tool using pair-wise correlations. Biotechnol Lett 26:509–515PubMedCrossRef Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP (2004) Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: best keeper–excel-based tool using pair-wise correlations. Biotechnol Lett 26:509–515PubMedCrossRef
26.
go back to reference Pitt CG, Gratzl MM, Kimmel GL, Surles J, Schindler A (1981) Aliphatic polyesters II. The degradation of poly (dl-lactide), poly (epsilon-caprolactone), and their copolymers in vivo. Biomaterials 2:215–220PubMedCrossRef Pitt CG, Gratzl MM, Kimmel GL, Surles J, Schindler A (1981) Aliphatic polyesters II. The degradation of poly (dl-lactide), poly (epsilon-caprolactone), and their copolymers in vivo. Biomaterials 2:215–220PubMedCrossRef
27.
go back to reference Reinholz GG, Lu L, Saris DB, Yaszemski MJ, O’Driscoll SW (2004) Animal models for cartilage reconstruction. Biomaterials 25:1511–1521PubMedCrossRef Reinholz GG, Lu L, Saris DB, Yaszemski MJ, O’Driscoll SW (2004) Animal models for cartilage reconstruction. Biomaterials 25:1511–1521PubMedCrossRef
28.
go back to reference Russlies M, Ruther P, Koller W, Stomberg P, Behrens P (2003) Biomechanical properties of cartilage repair tissue after different cartilage repair procedures in sheep. Z Orthop Ihre Grenzgeb 141:465–471PubMedCrossRef Russlies M, Ruther P, Koller W, Stomberg P, Behrens P (2003) Biomechanical properties of cartilage repair tissue after different cartilage repair procedures in sheep. Z Orthop Ihre Grenzgeb 141:465–471PubMedCrossRef
29.
go back to reference Shao XX, Hutmacher DW, Ho ST, Goh JC, Lee EH (2006) Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits. Biomaterials 27:1071–1080PubMedCrossRef Shao XX, Hutmacher DW, Ho ST, Goh JC, Lee EH (2006) Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits. Biomaterials 27:1071–1080PubMedCrossRef
30.
go back to reference Steinert AF, Ghivizzani SC, Rethwilm A, Tuan RS, Evans CH, Noth U (2007) Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res Ther 9:213PubMedCrossRef Steinert AF, Ghivizzani SC, Rethwilm A, Tuan RS, Evans CH, Noth U (2007) Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res Ther 9:213PubMedCrossRef
31.
go back to reference Woodward SC, Brewer PS, Moatamed F, Schindler A, Pitt CG (1985) The intracellular degradation of poly(epsilon-caprolactone). J Biomed Mater Res 19:437–444PubMedCrossRef Woodward SC, Brewer PS, Moatamed F, Schindler A, Pitt CG (1985) The intracellular degradation of poly(epsilon-caprolactone). J Biomed Mater Res 19:437–444PubMedCrossRef
32.
go back to reference Yamashita S, Andoh M, Ueno-Kudoh H, Sato T, Miyaki S, Asahara H (2009) Sox9 directly promotes Bapx1 gene expression to repress Runx2 in chondrocytes. Exp Cell Res 315:2231–2240PubMedCrossRef Yamashita S, Andoh M, Ueno-Kudoh H, Sato T, Miyaki S, Asahara H (2009) Sox9 directly promotes Bapx1 gene expression to repress Runx2 in chondrocytes. Exp Cell Res 315:2231–2240PubMedCrossRef
Metadata
Title
A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies
Authors
Bjørn Borsøe Christensen
Casper Bindzus Foldager
Ole Møller Hansen
Asger Albæk Kristiansen
Dang Quang Svend Le
Agnete Desirée Nielsen
Jens Vinge Nygaard
Cody Erik Bünger
Martin Lind
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 6/2012
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-011-1692-9

Other articles of this Issue 6/2012

Knee Surgery, Sports Traumatology, Arthroscopy 6/2012 Go to the issue