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.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Journal of Nanobiotechnology Open Access 18 March 2022
Journal of Materials Science: Materials in Medicine Open Access 10 August 2021
Friction Open Access 21 October 2020
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Mow, V. C., Ratcliffe, A. & Poole, A. R. Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials 13, 67–97 (1992).
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).
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).
Woo, S. L. et al. Large deformation nonhomogeneous and directional properties of articular cartilage in uniaxial tension. J. Biomech. 12, 437–446 (1979).
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).
Freed, L. E. et al. Biodegradable polymer scaffolds for tissue engineering. Nature Biotechnol. 12, 689–693 (1994).
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).
Ameer, G. A., Mahmood, T. A. & Langer, R. A biodegradable composite scaffold for cell transplantation. J. Orthop. Res. 20, 16–19 (2002).
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).
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).
Pei, M. et al. Bioreactors mediate the effectiveness of tissue engineering scaffolds. Faseb J. 16, 1691–1694 (2002).
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).
Tognana, E. et al. Adjacent tissues (cartilage, bone) affect the functional integration of engineered calf cartilage in vitro. Osteoarthritis Cartilage 13, 129–138 (2005).
Atala, A. et al. Injectable alginate seeded with chondrocytes as a potential treatment for vesicoureteral reflux. J. Urol. 150, 745–747 (1993).
Caterson, E. J. et al. Polymer/alginate amalgam for cartilage-tissue engineering. Ann. NY Acad. Sci. 961, 134–138 (2002).
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).
Paige, K. T. et al. De novo cartilage generation using calcium alginate-chondrocyte constructs. Plast. Reconstruct. Surgery 97, 168–180 (1996).
Rowley, J. A., Madlambayan, G. & Mooney, D. J. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20, 45–53 (1999).
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).
Hollister, S. J. Porous scaffold design for tissue engineering. Nature Mater. 4, 518–524 (2005).
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).
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).
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).
Benya, P. D. & Shaffer, J. D. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30, 215–224 (1982).
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).
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).
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).
Ateshian, G. A. A theoretical formulation for boundary friction in articular cartilage. J. Biomech. Eng. 119, 81–86 (1997).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Mow, V. C. & Guo, X. E. Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies. Annu. Rev. Biomed. Eng. 4, 175–209 (2002).
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).
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).
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).
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).
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).
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.
The authors declare no competing financial interests.
About this article
Cite this article
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
This article is cited by
Journal of Nanobiotechnology (2022)
Advanced Fiber Materials (2022)
Advanced Functional Polymers: Properties and Supramolecular Phenomena in Hydrogels and Polyrotaxane-based Materials
Chemistry Africa (2022)
Nature Computational Science (2021)