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Principles of Cell Mechanics for Cartilage Tissue Engineering

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Abstract

The critical importance of mechanical signals to the health and maintenance of articular cartilage has been well demonstrated. Tissue engineers have taken a cue from normal cartilage physiology and incorporated the use of mechanical stimulation into their attempts to engineer functional cartilage. However, the specific types of mechanical stimulation that are most beneficial, and the mechanisms that allow a chondrocyte to perceive and respond to those forces, have yet to be elucidated. To develop a better understanding of these processes, it is necessary to examine the mechanical behavior of the single chondrocyte. This paper reviews salient topics related to chondrocyte biomechanics and mechanotransduction, and attempts to put this information into a context both appropriate and useful to cartilage tissue engineering. It also describes the directions this exciting field is taking, and lays out a vision for future studies that could have a significant impact on our understanding of cartilage health and disease. © 2003 Biomedical Engineering Society.

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REFERENCES

  1. Bachrach, N. M., W. B. Valhmu, E. Stazzone, A. Ratcliffe, W. M. Lai, and V. C. Mow. Changes in proteoglycan synthesis of chondrocytes in articular cartilage are associated with the time­dependent changes in their mechanical environment. J. Biomech.28:1561­1569, 1995.­

    Google Scholar 

  2. Bader, D. L., T. Ohashi, M. M. Knight, D. A. Lee, and M. Sato. Deformation properties of articular chondrocytes: A critique of three separate techniques. Biorheology39:69­78, 2002.­

    Google Scholar 

  3. Bonassar, L. J., A. J. Grodzinsky, E. H. Frank, S. G. Davila, N. R. Bhaktav, and S. B. Trippel. The effect of dynamic compression on the response of articular cartilage to insulin­like growth factor I. J. Orthop. Res.19:11­17, 2001.­

    Google Scholar 

  4. Bonassar, L. J., A. J. Grodzinsky, A. Srinivasan, S. G. Davila, and S. B. Trippel. Mechanical and physicochemical regulation of the action of insulin­like growth factor I on articular cartilage. Arch. Biochem. Biophys.379:57­63, 2000.­

    Google Scholar 

  5. Breuls, R. G., B. G. Sengers, C. W. Oomens, C. V. Bouten, and F. P. Baaijens. Predicting local cell deformations in engineered tissue constructs: a multilevel finite element approach. J. Biomech. Eng.124:198­207, 2002.­

    Google Scholar 

  6. Browning, J. A., R. E. Walker, A. C. Hall, and R. J. Wilkins. Modulation of Na+ × H+ exchange by hydrostatic pressure in isolated bovine articular chondrocytes. Acta Physiol. Scand.166:39­45, 1999.­

    Google Scholar 

  7. Buschmann, M. D., Y. A. Gluzband, A. J. Grodzinsky, and E. B. Hunziker. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J. Cell. Sci.108:1497­1508, 1995.­

    Google Scholar 

  8. Buschmann, M. D., E. B. Hunziker, Y. J. Kim, and A. J. Grodzinsky. Altered aggrecan synthesis correlates with cell and nucleus structure in statically compressed cartilage. J. Cell. Sci.109:499­508, 1996.­

    Google Scholar 

  9. Buschmann, M. D., Y. J. Kim, M. Wong, E. Frank, E. B. Hunziker, and A. J. Grodzinsky. Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow. Arch. Biochem. Biophys.366:1­7, 1999.­

    Google Scholar 

  10. Carver, S. E., and C. A. Heath. Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure. Biotechnol. Bioeng.62:166­174, 1999.­

    Google Scholar 

  11. Carver, S. E., and C. A. Heath. Influence of intermittent pressure, fluid flow, and mixing on the regenerative properties of articular chondrocytes. Biotechnol. Bioeng.65:274­281, 1999.­

    Google Scholar 

  12. D'Andrea, P., A. Calabrese, I. Capozzi, M. Grandolfo, R. Tonon, and F. Vittur. Intercellular Ca2+ waves in mechanically stimulated articular chondrocytes. Biorheology37:75­83, 2000.­

    Google Scholar 

  13. Durrant, L. A., C. W. Archer, M. Benjamin, and J. R. Ralphs. Organization of the chondrocyte cytoskeleton and its response to changing mechanical conditions in organ culture. J. Anat.194:343­353, 1999.­

    Google Scholar 

  14. Freeman, P. M., R. N. Natarajan, J. H. Kimura, and T. P. Andriacchi. Chondrocyte cells respond mechanically to compressive loads. J. Orthop. Res.12:311­320, 1994.­

    Google Scholar 

  15. Gooch, K. J., T. Blunk, D. L. Courter, A. L. Sieminski, P. M. Bursac, G. Vunjak­Novakovic, and L. E. Freed. IGF­I and mechanical environment interact to modulate engineered cartilage development. Biochem. Biophys. Res. Commun.286:909­915, 2001.­

    Google Scholar 

  16. Gray, M. L., A. M. Pizzanelli, A. J. Grodzinsky, and R. C. Lee. Mechanical and physiochemical determinants of the chondrocyte biosynthetic response. J. Orthop. Res.6:777­792, 1988.­

    Google Scholar 

  17. Guilak, F.Compression­induced changes in the shape and volume of the chondrocyte nucleus. J. Biomech.28:1529­1541, 1995.­

    Google Scholar 

  18. Guilak, F., L. Alexopoulos, R. Nielsen, H. P. Ting­Beall, and M. Haider. The biomechanical properties of the chondrocyte pericellular matrix: micropipette aspiration of mechanically isolated chondrons. Trans. Orthop. Res. Soc.27:107, 2003.­

    Google Scholar 

  19. Guilak, F., G. R. Erickson, and H. P. Ting­Beall. The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes. Biophys. J.82:720­727, 2002.­

    Google Scholar 

  20. Guilak, F., W. R. Jones, H. P. Ting­Beall, and G. M. Lee. The deformation behavior and mechanical properties of chondrocytes in articular cartilage. Osteoarthritis Cartilage7:59­70, 1999.­

    Google Scholar 

  21. Guilak, F., and V. C. Mow. The mechanical environment of the chondrocyte: A biphasic finite element model of cell­matrix interactions in articular cartilage. J. Biomech.33:1663­1673, 2000.­

    Google Scholar 

  22. Guilak, F., A. Ratcliffe, and V. C. Mow. Chondrocyte deformation and local tissue strain in articular cartilage: A confocal microscopy study. J. Orthop. Res.13:410­421, 1995.­

    Google Scholar 

  23. Guilak, F., M. Sato, C. M. Stanford, and R. A. Brand. Cell mechanics. J. Biomech.33:1­2, 2000.­

    Google Scholar 

  24. Guilak, F., J. R. Tedrow, and R. Burgkart. Viscoelastic properties of the cell nucleus. Biochem. Biophys. Res. Commun.269:781­786, 2000.­

    Google Scholar 

  25. Haider, M. A., and F. Guilak. An axisymmetric boundary integral model for incompressible linear viscoelasticity: Application to the micropipette aspiration contact problem. J. Biomech. Eng.122:236­244, 2000.­

    Google Scholar 

  26. Hall, A. C.Differential effects of hydrostatic pressure on cation transport pathways of isolated articular chondrocytes. J. Cell Physiol.178:197­204, 1999.­

    Google Scholar 

  27. Hansen, U., M. Schunke, C. Domm, N. Ioannidis, J. Hassenpflug, T. Gehrke, and B. Kurz. Combination of reduced oxygen tension and intermittent hydrostatic pressure: A useful tool in articular cartilage tissue engineering. J. Biomech.34:941­949, 2001.­

    Google Scholar 

  28. Idowu, B. D., M. M. Knight, D. L. Bader, and D. A. Lee. Confocal analysis of cytoskeletal organization within isolated chondrocyte subpopulations cultured in agarose. Histochem. J.32:165­174, 2000.­

    Google Scholar 

  29. Jin, M., E. H. Frank, T. M. Quinn, E. B. Hunziker, and A. J. Grodzinsky. Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants. Arch. Biochem. Biophys.395:41­48, 2001.­

    Google Scholar 

  30. Jones, W. R., H. P. Ting­Beall, G. M. Lee, S. S. Kelley, R. M. Hochmuth, and F. Guilak. Alterations in the Young's modulus and volumetric properties of chondrocytes isolated from normal and osteoarthritic human cartilage. J. Biomech.32:119­127, 1999.­

    Google Scholar 

  31. Jortikka, M. O., J. J. Parkkinen, R. I. Inkinen, J. Karner, H. T. Jarvelainen, L. O. Nelimarkka, M. I. Tammi, and M. J. Lammi. The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure. Arch. Biochem. Biophys.374:172­180, 2000.­

    Google Scholar 

  32. Kim, Y. J., L. J. Bonassar, and A. J. Grodzinsky. The role of cartilage streaming potential, fluid flow, and pressure in the stimulation of chondrocyte biosynthesis during dynamic compression. J. Biomech.28:1055­1066, 1995.­

    Google Scholar 

  33. Kim, Y. J., R. L. Sah, A. J. Grodzinsky, A. H. Plaas, and J. D. Sandy. Mechanical regulation of cartilage biosynthetic behavior: physical stimuli. Arch. Biochem. Biophys.311:1­12, 1994.­

    Google Scholar 

  34. Knight, M. M., D. A. Lee, and D. L. Bader. The influence of elaborated pericellular matrix on the deformation of isolated articular chondrocytes cultured in agarose. Biochim. Biophys. Acta1405:67­77, 1998.­

    Google Scholar 

  35. Knight, M. M., J. M. Ross, A. F. Sherwin, D. A. Lee, D. L. Bader, and C. A. Poole. Chondrocyte deformation within mechanically and enzymatically extracted chondrons compressed in agarose. Biochim. Biophys. Acta1526:141­146, 2001.­

    Google Scholar 

  36. Knight, M. M., J. van de Breevaart Bravenboer, D. A. Lee, G. J. van Osch, H. Weinans, and D. L. Bader. Cell and nucleus deformation in compressed chondrocyte­alginate constructs: Temporal changes and calculation of cell modulus. Biochim. Biophys. Acta1570:1­8, 2002.­

    Google Scholar 

  37. Koay, E. J., A. C. Shieh, and K. A. Athanasiou. Creep indentation of single cells. (in review).­

  38. Lai, W. M., V. C. Mow, D. D. Sun, and G. A. Ateshian. On the electric potentials inside a charged soft hydrated biological tissue: streaming potential versus diffusion potential. J. Biomech. Eng.122:336­346, 2000.­

    Google Scholar 

  39. Langelier, E., R. Suetterlin, C. D. Hoemann, U. Aebi, and M. D. Buschmann. The chondrocyte cytoskeleton in mature articular cartilage: Structure and distribution of actin, tubulin, and vimentin filaments. J. Histochem. Cytochem.48:1307­1320, 2000.­

    Google Scholar 

  40. LeBaron, R. G., and K. A. Athanasiou. Extracellular matrix cell adhesion peptides: Functional applications in orthopedic materials. Tissue Eng.6:85­103, 2000.­

    Google Scholar 

  41. Lee, D. A., M. M. Knight, J. F. Bolton, B. D. Idowu, M. V. Kayser, and D. L. Bader. Chondrocyte deformation within compressed agarose constructs at the cellular and subcellular levels. J. Biomech.33:81­95, 2000.­

    Google Scholar 

  42. Lee, D. A., T. Noguchi, M. M. Knight, L. O'Donnell, G. Bentley, and D. L. Bader. Response of chondrocyte subpopulations cultured within unloaded and loaded agarose. J. Orthop. Res.16:726­733, 1998.­

    Google Scholar 

  43. Lee, H. S., S. J. Millward­Sadler, M. O. Wright, G. Nuki, and D. M. Salter. Integrin and mechanosensitive ion channel­dependent tyrosine phosphorylation of focal adhesion proteins and beta­catenin in human articular chondrocytes after mechanical stimulation. J. Bone Miner. Res.15:1501­1509, 2000.­

    Google Scholar 

  44. Mauck, R. L., M. A. Soltz, C. C. Wang, D. D. Wong, P. H. Chao, W. B. Valhmu, C. T. Hung, and G. A. Ateshian. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte­seeded agarose gels. J. Biomech. Eng.122:252­260, 2000.­

    Google Scholar 

  45. Millward­Sadler, S. J., M. O. Wright, L. W. Davies, G. Nuki, and D. M. Salter. Mechanotransduction via integrins and interleukin­4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes. Arthritis Rheum.43:2091­2099, 2000.­

    Google Scholar 

  46. Millward­Sadler, S. J., M. O. Wright, H. Lee, K. Nishida, H. Caldwell, G. Nuki, and D. M. Salter. Integrin­regulated secretion of interleukin 4: A novel pathway of mechanotransduction in human articular chondrocytes. J. Cell Biol.145:183­189, 1999.­

    Google Scholar 

  47. Mow, V. C., S. C. Kuei, W. M. Lai, and C. G. Armstrong. Biphasic creep and stress relaxation of articular cartilage in compression. Theory and experiments. J. Biomech. Eng.102:73­84, 1980.­

    Google Scholar 

  48. Parkkinen, J. J., J. Ikonen, M. J. Lammi, J. Laakkonen, M. Tammi, and H. J. Helminen. Effects of cyclic hydrostatic pressure on proteoglycan synthesis in cultured chondrocytes and articular cartilage explants. Arch. Biochem. Biophys.300:458­465, 1993.­

    Google Scholar 

  49. Parkkinen, J. J., M. J. Lammi, H. J. Helminen, and M. Tammi. Local stimulation of proteoglycan synthesis in articular cartilage explants by dynamic compression. J. Orthop. Res.10:610­620, 1992.­

    Google Scholar 

  50. Sah, R. L., Y. J. Kim, J. Y. Doong, A. J. Grodzinsky, A. H. Plaas, and J. D. Sandy. Biosynthetic response of cartilage explants to dynamic compression. J. Orthop. Res.7:619­636, 1989.­

    Google Scholar 

  51. Salter, D. M., S. J. Millward­Sadler, G. Nuki, and M. O. Wright. Integrin­interleukin­4 mechanotransduction pathways in human chondrocytes. Clin. Orthop. Relat. Res.391:S49­60, 2001.­

    Google Scholar 

  52. Sato, M., D. P. Theret, L. T. Wheeler, N. Ohshima, and R. M. Nerem. Application of the micropipette technique to the measurement of cultured porcine aortic endothelial cell viscoelastic properties. J. Biomech. Eng.112:263­268, 1990.­

    Google Scholar 

  53. Schinagl, R. M., D. Gurskis, R. M. Schinagl, A. C. Chen, and R. L. Sah. Depth­dependent confined compression modulus of full­thickness bovine articular cartilage. J. Orthop. Res.15:499­506, 1997.­

    Google Scholar 

  54. Shin, D., and K. Athanasiou. Cytoindentation for obtaining cell biomechanical properties. J. Orthop. Res.17:880­890, 1999.­

    Google Scholar 

  55. Smith, R. L., B. S. Donlon, M. K. Gupta, M. Mohtai, P. Das, D. R. Carter, J. Cooke, G. Gibbons, N. Hutchinson, and D. J. Schurman. Effects of fluid­induced shear on articular chondrocyte morphology and metabolism. J. Orthop. Res.13:824­831, 1995.­

    Google Scholar 

  56. Smith, R. L., J. Lin, M. C. Trindade, J. Shida, G. Kajiyama, T. Vu, A. R. Hoffman, M. C. van der Meulen, S. B. Goodman, D. J. Schurman, and D. R. Carter. Time­dependent effects of intermittent hydrostatic pressure on articular chondrocyte type II collagen and aggrecan mRNA expression. J. Rehabil. Res. Dev.37:153­161, 2000.­

    Google Scholar 

  57. Smith, R. L., S. F. Rusk, B. E. Ellison, P. Wessells, K. Tsuchiya, D. R. Carter, W. E. Caler, L. J. Sandell, and D. J. Schurman. stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure.J. Orthop. Res.14:53­60, 1996.­

    Google Scholar 

  58. Theret, D. P., M. J. Levesque, M. Sato, R. M. Nerem, and L. T. Wheeler. The application of a homogeneous half­space model in the analysis of endothelial cell micropipette measurements. J. Biomech. Eng.110:190­199, 1988.­

    Google Scholar 

  59. Trickey, T. R., M. Lee, and T. Guilak. Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage. J. Orthop. Res.18:891­898, 2000.­

    Google Scholar 

  60. Vunjak­Novakovic, G., I. Martin, B. Obradovic, S. Treppo, A. J. Grodzinsky, R. Langer, and L. E. Freed. Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue­engineered cartilage. J. Orthop. Res.17:130­138, 1999.­

    Google Scholar 

  61. Wang, C. C., X. E. Guo, D. Sun, V. C. Mow, G. A. Ateshian, and C. T. Hung. The functional environment of chondrocytes within cartilage subjected to compressive loading: A theoretical and experimental approach. Biorheology39:11­25, 2002.­

    Google Scholar 

  62. Wright, M. O., K. Nishida, C. Bavington, J. L. Godolphin, E. Dunne, S. Walmsley, P. Jobanputra, G. Nuki, and D. M. Salter. Hyperpolarization of cultured human chondrocytes following cyclical pressure­induced strain: Evidence of a role for alpha 5 beta 1 integrin as a chondrocyte mechanoreceptor. J. Orthop. Res.15:742­747, 1997.­

    Google Scholar 

  63. Wright, M. O., R. A. Stockwell, and G. Nuki. Response of plasma membrane to applied hydrostatic pressure in chondrocytes and fibroblasts. Connect. Tissue Res.28:49­70, 1992.­

    Google Scholar 

  64. Wu, J. Z., and W. Herzog. Finite element simulation of location­ and time­dependent mechanical behavior of chondrocytes in unconfined compression tests. Ann. Biomed. Eng.28:318­330, 2000.­

    Google Scholar 

  65. Wu, J. Z., W. Herzog, and M. Epstein. Modeling of location­ and time­dependent deformation of chondrocytes during cartilage loading. J. Biomech.32:563­572, 1999.­

    Google Scholar 

  66. Yellowley, C. E., C. R. Jacobs, Z. Li, Z. Zhou, and H. J. Donahue. Effects of fluid flow on intracellular calcium in bovine articular chondrocytes. Am. J. Physiol.273:C30­36, 1997.­ ­

    Google Scholar 

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Shieh, A.C., Athanasiou, K.A. Principles of Cell Mechanics for Cartilage Tissue Engineering. Annals of Biomedical Engineering 31, 1–11 (2003). https://doi.org/10.1114/1.1535415

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