Integration of engineered cartilage

The structure and function of cartilaginous constructs, engineered in vitro using bovine articular chondrocytes, biodegradable scaffolds and bioreactors, can be modulated by the conditions and duration of tissue cultivation. We hypothesized that the integrative properties of engineered cartilage depend on developmental stage of the construct and the extracellular matrix content of adjacent cartilage, and that some aspects of integration can be studied under controlled in vitro conditions. Disc‐shaped constructs (cultured for 5±1 days or 5±1 weeks) or explants (untreated or trypsin treated cartilage) were sutured into ring‐shaped explants (untreated or trypsin treated cartilage) to form composites that were cultured for an additional 1‐8 weeks in bioreactors and evaluated biochemically, histologically and mechanically (compressive stiffness of the central disk, adhesive strength of the integration interface). Immature constructs had poorer mechanical properties but integrated better than either more mature constructs or cartilage explants. Integration of immature constructs involved cell proliferation and the progressive formation of cartilaginous tissue, in contrast to the integration of more mature constructs or native cartilage which involved only the secretion of extracellular matrix components. Integration patterns correlated with the adhesive strength of the disc‐ring interface, which was markedly higher for immature constructs than for either more mature constructs or cartilage explants. Trypsin treatment of the adjacent cartilage further enhanced the integration of immature constructs. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

[1]  Robert Langer,et al.  Biodegradable Polymer Scaffolds for Tissue Engineering , 1994, Bio/Technology.

[2]  G. Vunjak‐Novakovic,et al.  Culture of organized cell communities. , 1998, Advanced drug delivery reviews.

[3]  J. Abbott,et al.  THE LOSS OF PHENOTYPIC TRAITS BY DIFFERENTIATED CELLS , 1966, The Journal of cell biology.

[4]  J. F. Woessner,et al.  The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. , 1961, Archives of biochemistry and biophysics.

[5]  H J Mankin,et al.  Articular cartilage repair and transplantation. , 1998, Arthritis and rheumatism.

[6]  Joseph M. Mansour,et al.  Mesenchymal Cell-Based Repair of Large Full Thickness Defects of Articular Cartilage , 1994 .

[7]  R Langer,et al.  In vitro generation of osteochondral composites. , 2000, Biomaterials.

[8]  Albert C. Chen,et al.  Integrative repair of articular cartilage in vitro: Adhesive strength of the interface region , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  A. Grodzinsky,et al.  Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[10]  C. Rorabeck,et al.  Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. , 1994, The Journal of clinical investigation.

[11]  K. Mark,et al.  Study of differential collagen synthesis during development of the chick embryo by immunofluorescence. I. Preparation of collagen type I and type II specific antibodies and their application to early stages of the chick embryo. , 1976 .

[12]  D. Zaleske,et al.  Bonding of cartilage matrices with cultured chondrocytes: An experimental model , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[13]  G. Vunjak‐Novakovic,et al.  Tissue engineering of cartilage in space. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[14]  B. Obradovic,et al.  Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue‐engineered cartilage , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  Gordana Vunjak-Novakovic,et al.  CHAPTER 13 – TISSUE ENGINEERING BIOREACTORS , 2000 .

[16]  T Ochi,et al.  Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. , 1989, The Journal of bone and joint surgery. British volume.

[17]  J. Abbott,et al.  The loss of phenotypic traits by differentiated cells, V. The effect of 5-bromodeoxyuridine on cloned chondrocytes. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Grodzinsky,et al.  Fluorometric assay of DNA in cartilage explants using Hoechst 33258. , 1988, Analytical biochemistry.

[19]  P. D. Di Cesare,et al.  Repair of articular cartilage defects: part II. Treatment options. , 1999, American journal of orthopedics.

[20]  R Langer,et al.  Dynamic Cell Seeding of Polymer Scaffolds for Cartilage Tissue Engineering , 1998, Biotechnology progress.

[21]  S. O’Driscoll Current Concepts Review - The Healing and Regeneration of Articular Cartilage* , 1998 .

[22]  M. Yamagata,et al.  Regulation of cell-substrate adhesion by proteoglycans immobilized on extracellular substrates. , 1989, The Journal of biological chemistry.

[23]  M. Müller,et al.  Removal of proteoglycans from the surface of defects in articular cartilage transiently enhances coverage by repair cells. , 1998, The Journal of bone and joint surgery. British volume.

[24]  J. Abbott,et al.  THE LOSS OF PHENOTYPIC TRAITS BY DIFFERENTIATED CELLS IN VITRO, I. DEDIFFERENTIATION OF CARTILAGE CELLS. , 1960, Proceedings of the National Academy of Sciences of the United States of America.

[25]  E. Hunziker,et al.  Removal of proteoglycans from the surface of defects in articular cartilage transiently enhances coverage by repair cells , 1998 .

[26]  R Langer,et al.  Chondrogenesis in a cell-polymer-bioreactor system. , 1998, Experimental cell research.

[27]  G. Weissmann,et al.  Cartilage proteoglycans inhibit fibronectin-mediated adhesion , 1981, Nature.

[28]  B. Hall Developmental and cellular skeletal biology , 1978 .

[29]  A. Grodzinsky,et al.  Biosynthetic response of cartilage explants to dynamic compression , 1989, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  G. Vunjak‐Novakovic,et al.  Cultivation of cell–polymer tissue constructs in simulated microgravity , 1995, Biotechnology and bioengineering.

[31]  G. Vunjak‐Novakovic,et al.  Frontiers in tissue engineering. In vitro modulation of chondrogenesis. , 1999, Clinical orthopaedics and related research.

[32]  E. Hunziker,et al.  Repair of Partial-Thickness Defects in Articular Cartilage: Cell Recruitment from the Synovial Membrane* , 1996, The Journal of bone and joint surgery. American volume.

[33]  D. Buttle,et al.  Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. , 1986, Biochimica et biophysica acta.

[34]  C. Sledge,et al.  Healing of chondral and osteochondral defects in a canine model: the role of cultured chondrocytes in regeneration of articular cartilage. , 1996, Biomaterials.

[35]  A. Grodzinsky,et al.  Cartilage electromechanics--I. Electrokinetic transduction and the effects of electrolyte pH and ionic strength. , 1987, Journal of biomechanics.