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A biomimetic three-dimensional woven composite scaffold for functional tissue engineering of cartilage

Nature Materials volume 6, pages 162–167 (2007)Cite this article

Abstract

Tissue engineering seeks to repair or regenerate tissues through combinations of implanted cells, biomaterial scaffolds and biologically active molecules. The rapid restoration of tissue biomechanical function remains an important challenge, emphasizing the need to replicate structural and mechanical properties using novel scaffold designs. Here we present a microscale 3D weaving technique to generate anisotropic 3D woven structures as the basis for novel composite scaffolds that are consolidated with a chondrocyte–hydrogel mixture into cartilage tissue constructs. Composite scaffolds show mechanical properties of the same order of magnitude as values for native articular cartilage, as measured by compressive, tensile and shear testing. Moreover, our findings showed that porous composite scaffolds could be engineered with initial properties that reproduce the anisotropy, viscoelasticity and tension–compression nonlinearity of native articular cartilage. Such scaffolds uniquely combine the potential for load-bearing immediately after implantation in vivo with biological support for cell-based tissue regeneration without requiring cultivation in vitro.

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Figure 1: Fibre architecture of a 3D orthogonally woven structure.
Figure 2: Fluorescent image of a freshly seeded construct.
Figure 3: Effects of fibre reinforcement on compressive and shear mechanical properties.
Figure 4: Effects of fibre reinforcement on tensile properties.

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References

  1. Mow, V. C., Ratcliffe, A. & Poole, A. R. Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials 13, 67–97 (1992).

    Article  CAS  Google Scholar 

  2. Mow, V. C., Kuei, S. C., Lai, W. M. & Armstrong, C. G. Biphasic creep and stress relaxation of articular cartilage in compression? Theory and experiments. J. Biomech. Eng. 102, 73–84 (1980).

    Article  CAS  Google Scholar 

  3. Soltz, M. A. & Ateshian, G. A. A conewise linear elasticity mixture model for the analysis of tension-compression nonlinearity in articular cartilage. J. Biomech. Eng. 122, 576–586 (2000).

    Article  CAS  Google Scholar 

  4. Woo, S. L. et al. Large deformation nonhomogeneous and directional properties of articular cartilage in uniaxial tension. J. Biomech. 12, 437–446 (1979).

    Article  CAS  Google Scholar 

  5. Guilak, F., Butler, D. L. & Goldstein, S. A. Functional tissue engineering: the role of biomechanics in articular cartilage repair. Clin. Orthop. Relat. Res. S295–S305 (2001).

  6. Freed, L. E. et al. Biodegradable polymer scaffolds for tissue engineering. Nature Biotechnol. 12, 689–693 (1994).

    Article  CAS  Google Scholar 

  7. Buschmann, M. D., Gluzband, Y. A., Grodzinsky, A. J., Kimura, J. H. & Hunziker, E. B. Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix. J. Orthop. Res. 10, 745–758 (1992).

    Article  CAS  Google Scholar 

  8. Ameer, G. A., Mahmood, T. A. & Langer, R. A biodegradable composite scaffold for cell transplantation. J. Orthop. Res. 20, 16–19 (2002).

    Article  CAS  Google Scholar 

  9. Freed, L. E., Langer, R., Martin, I., Pellis, N. R. & Vunjak-Novakovic, G. Tissue engineering of cartilage in space. Proc. Natl Acad. Sci. USA 94, 13885–13890 (1997).

    Article  CAS  Google Scholar 

  10. Gao, J., Dennis, J. E., Solchaga, L. A., Goldberg, V. M. & Caplan, A. I. Repair of osteochondral defect with tissue-engineered two-phase composite material of injectable calcium phosphate and hyaluronan sponge. Tissue Eng. 8, 827–837 (2002).

    Article  CAS  Google Scholar 

  11. Pei, M. et al. Bioreactors mediate the effectiveness of tissue engineering scaffolds. Faseb J. 16, 1691–1694 (2002).

    Article  CAS  Google Scholar 

  12. Vunjak-Novakovic, G. et al. Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage. J. Orthop. Res. 17, 130–138 (1999).

    Article  CAS  Google Scholar 

  13. Tognana, E. et al. Adjacent tissues (cartilage, bone) affect the functional integration of engineered calf cartilage in vitro. Osteoarthritis Cartilage 13, 129–138 (2005).

    Article  CAS  Google Scholar 

  14. Atala, A. et al. Injectable alginate seeded with chondrocytes as a potential treatment for vesicoureteral reflux. J. Urol. 150, 745–747 (1993).

    Article  CAS  Google Scholar 

  15. Caterson, E. J. et al. Polymer/alginate amalgam for cartilage-tissue engineering. Ann. NY Acad. Sci. 961, 134–138 (2002).

    Article  CAS  Google Scholar 

  16. Mauck, R. L. et al. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J. Biomech. Eng. 122, 252–260 (2000).

    Article  CAS  Google Scholar 

  17. Paige, K. T. et al. De novo cartilage generation using calcium alginate-chondrocyte constructs. Plast. Reconstruct. Surgery 97, 168–180 (1996).

    Article  CAS  Google Scholar 

  18. Rowley, J. A., Madlambayan, G. & Mooney, D. J. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20, 45–53 (1999).

    Article  CAS  Google Scholar 

  19. Marijnissen, W. J. et al. Alginate as a chondrocyte-delivery substance in combination with a non-woven scaffold for cartilage tissue engineering. Biomaterials 23, 1511–1517 (2002).

    Article  CAS  Google Scholar 

  20. Hollister, S. J. Porous scaffold design for tissue engineering. Nature Mater. 4, 518–524 (2005).

    Article  CAS  Google Scholar 

  21. LeRoux, M. A., Guilak, F. & Setton, L. A. Compressive and shear properties of alginate gel: effects of sodium ions and alginate concentration. J. Biomed. Mater. Res. 47, 46–53 (1999).

    Article  CAS  Google Scholar 

  22. Mohamed, M. H., Bogdanovich, A. E., Dickinson, L. C., Singletary, J. N. & Lienhart, R. B. A new generation of 3D woven fabric preforms and composites. Sampe. J. 37, 8–17 (2001).

    Google Scholar 

  23. Aufderheide, A. C. & Athanasiou, K. A. Comparison of scaffolds and culture conditions for tissue engineering of the knee meniscus. Tissue Eng. 11, 1095–1104 (2005).

    Article  CAS  Google Scholar 

  24. Benya, P. D. & Shaffer, J. D. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30, 215–224 (1982).

    Article  CAS  Google Scholar 

  25. Lee, D. A. & Bader, D. L. Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose. J. Orthop. Res. 15, 181–188 (1997).

    Article  Google Scholar 

  26. Cohen, B., Lai, W. M. & Mow, V. C. A transversely isotropic biphasic model for unconfined compression of growth plate and chondroepiphysis. J. Biomech. Eng. 120, 491–496 (1998).

    Article  CAS  Google Scholar 

  27. Huang, C. Y., Stankiewicz, A., Ateshian, G. A. & Mow, V. C. Anisotropy, inhomogeneity, and tension-compression nonlinearity of human glenohumeral cartilage in finite deformation. J. Biomech. 38, 799–809 (2005).

    Article  Google Scholar 

  28. Ateshian, G. A. A theoretical formulation for boundary friction in articular cartilage. J. Biomech. Eng. 119, 81–86 (1997).

    Article  CAS  Google Scholar 

  29. Soltz, M. A. & Ateshian, G. A. Experimental verification and theoretical prediction of cartilage interstitial fluid pressurization at an impermeable contact interface in confined compression. J. Biomech. 31, 927–934 (1998).

    Article  CAS  Google Scholar 

  30. Li, W. J., Jiang, Y. J. & Tuan, R. S. Chondrocyte phenotype in engineered fibrous matrix is regulated by fiber size. Tissue Eng. 12, 1775–1785 (2006).

    Article  CAS  Google Scholar 

  31. Gu, W. Y., Yao, H., Huang, C. Y. & Cheung, H. S. New insight into deformation-dependent hydraulic permeability of gels and cartilage, and dynamic behavior of agarose gels in confined compression. J. Biomech. 36, 593–598 (2003).

    Article  CAS  Google Scholar 

  32. Akizuki, S. et al. Tensile properties of human knee joint cartilage: I. Influence of ionic conditions, weight bearing, and fibrillation on the tensile modulus. J. Orthop. Res. 4, 379–392 (1986).

    Article  CAS  Google Scholar 

  33. Kempson, G. E., Tuke, M. A., Dingle, J. T., Barrett, A. J. & Horsfield, P. H. The effects of proteolytic enzymes on the mechanical properties of adult human articular cartilage. Biochim. Biophys. Acta 428, 741–760 (1976).

    Article  CAS  Google Scholar 

  34. Below, S., Arnoczky, S. P., Dodds, J., Kooima, C. & Walter, N. The split-line pattern of the distal femur: A consideration in the orientation of autologous cartilage grafts. Arthroscopy 18, 613–617 (2002).

    Article  Google Scholar 

  35. Elliott, D. M., Guilak, F., Vail, T. P., Wang, J. Y. & Setton, L. A. Tensile properties of articular cartilage are altered by meniscectomy in a canine model of osteoarthritis. J. Orthop. Res. 17, 503–508 (1999).

    Article  CAS  Google Scholar 

  36. Guilak, F., Ratcliffe, A., Lane, N., Rosenwasser, M. P. & Mow, V. C. Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis. J. Orthop. Res. 12, 474–484 (1994).

    Article  CAS  Google Scholar 

  37. LeRoux, M. A. et al. Simultaneous changes in the mechanical properties, quantitative collagen organization, and proteoglycan concentration of articular cartilage following canine meniscectomy. J. Orthop. Res. 18, 383–392 (2000).

    Article  CAS  Google Scholar 

  38. Zhu, W., Mow, V. C., Koob, T. J. & Eyre, D. R. Viscoelastic shear properties of articular cartilage and the effects of glycosidase treatments. J. Orthop. Res. 11, 771–781 (1993).

    Article  CAS  Google Scholar 

  39. Bader, D. L., Kempson, G. E., Barrett, A. J. & Webb, W. The effects of leucocyte elastase on the mechanical properties of adult human articular cartilage in tension. Biochim. Biophys. Acta 677, 103–108 (1981).

    Article  CAS  Google Scholar 

  40. Setton, L. A., Mow, V. C., Muller, F. J., Pita, J. C. & Howell, D. S. Mechanical properties of canine articular cartilage are significantly altered following transection of the anterior cruciate ligament. J. Orthop. Res. 12, 451–463 (1994).

    Article  CAS  Google Scholar 

  41. Elliott, D. M., Narmoneva, D. A. & Setton, L. A. Direct measurement of the Poisson’s ratio of human patella cartilage in tension. J. Biomech. Eng. 124, 223–228 (2002).

    Article  Google Scholar 

  42. Huang, C. Y., Mow, V. C. & Ateshian, G. A. The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage. J. Biomech. Eng. 123, 410–417 (2001).

    Article  CAS  Google Scholar 

  43. Huang, C. Y., Soltz, M. A., Kopacz, M., Mow, V. C. & Ateshian, G. A. Experimental verification of the roles of intrinsic matrix viscoelasticity and tension-compression nonlinearity in the biphasic response of cartilage. J. Biomech. Eng. 125, 84–93 (2003).

    Article  Google Scholar 

  44. Mow, V. C. & Guo, X. E. Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies. Annu. Rev. Biomed. Eng. 4, 175–209 (2002).

    Article  CAS  Google Scholar 

  45. Athanasiou, K. A., Rosenwasser, M. P., Buckwalter, J. A., Malinin, T. I. & Mow, V. C. Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. J. Orthop. Res. 9, 330–340 (1991).

    Article  CAS  Google Scholar 

  46. Setton, L. A., Zhu, W. & Mow, V. C. The biphasic poroviscoelastic behavior of articular cartilage: role of the surface zone in governing the compressive behavior. J. Biomech. 26, 581–592 (1993).

    Article  CAS  Google Scholar 

  47. Athanasiou, K. A., Agarwal, A. & Dzida, F. J. Comparative study of the intrinsic mechanical properties of the human acetabular and femoral head cartilage. J. Orthop. Res. 12, 340–349 (1994).

    Article  CAS  Google Scholar 

  48. Jurvelin, J. S., Buschmann, M. D. & Hunziker, E. B. Optical and mechanical determination of Poisson’s ratio of adult bovine humeral articular cartilage. J. Biomech. 30, 235–241 (1997).

    Article  CAS  Google Scholar 

  49. Setton, L. A., Mow, V. C. & Howell, D. S. Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament. J. Orthop. Res. 13, 473–482 (1995).

    Article  CAS  Google Scholar 

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Acknowledgements

Supported by NIH grants AR49294, AR50245, AG15768 and AR48182, NASA grant NNJ04HC72G and a Translational Research Partnership from the Wallace H. Coulter Foundation. The authors thank J. Perera and R. Catz for technical assistance, B. Tawil of Baxter Biosurgery for providing the Tisseel Y used in this study, L. Eibest for assistance with scanning electron microscopy and L. Setton for advice on the mechanical testing.

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Authors and Affiliations

  1. Department of Surgery, 375 MSRB, Box 3093, Duke University Medical Center, Durham, North Carolina, 27710, USA

    Franklin T. Moutos & Farshid Guilak

  2. Department of Biomedical Engineering, 375 MSRB, Box 3093, Duke University Medical Center, Durham, North Carolina, 27710, USA

    Franklin T. Moutos & Farshid Guilak

  3. Harvard-MIT Division of Health Sciences & Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building E25-330, Cambridge, Massachusetts, 02139, USA

    Lisa E. Freed

  4. Department of Mechanical Engineering & Materials Science, 375 MSRB, Box 3093, Duke University Medical Center, Durham, North Carolina, 27710, USA

    Farshid Guilak

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  1. Franklin T. Moutos
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Correspondence to Farshid Guilak.

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Moutos, F., Freed, L. & Guilak, F. A biomimetic three-dimensional woven composite scaffold for functional tissue engineering of cartilage. Nature Mater 6, 162–167 (2007). https://doi.org/10.1038/nmat1822

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