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Remodeling of Engineered Tissue Anisotropy in Response to Altered Loading Conditions

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Abstract

Structural and mechanical anisotropy are critical to the function of many engineered tissues. This study examined the ability of anisotropic tissue constructs to overcome contact guidance cues and remodel in response to altered mechanical loading conditions. Square tissues engineered from dermal fibroblasts and type-I collagen were uniaxially loaded to induce cell and matrix alignment. After an initial time, t*, of 5–72 h, loading was switched from the x-axis to the y-axis. Cell alignment was examined throughout the experiment until a steady state was reached. Before t*, cells spontaneously aligned in the x-direction. After t*, the strength of alignment transiently decreased then increased, and mean cell orientation transitioned from the x- to the y-direction following an exponential time course with a time constant that increased with t*. Collagen fiber orientation exhibited similar trends that could not be explained by passive kinematics alone. Structural realignment resulted in concomitant changes in biaxial tissue mechanical properties. The findings suggest that even highly aligned engineered tissue constructs retain the capacity to remodel in response to altered mechanical stimuli. This may have important functional consequences when an anisotropic engineered tissue designed in vitro is surgically implanted into a mechanically complex graft site.

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References

  1. Barocas V. H., T. S. Girton, R. T. Tranquillo 1998 Engineered alignment in media equivalents: magnetic prealignment and mandrel compaction. J. Biomech. Eng. 120:660–666

    Article  PubMed  CAS  Google Scholar 

  2. Barocas V. H., R. T. Tranquillo 1997 An anisotropic biphasic theory of tissue-equivalent mechanics: the interplay among cell traction, fibrillar network deformation, fibril alignment, and cell contact guidance. J. Biomech. Eng. 119:137–145

    Article  PubMed  CAS  Google Scholar 

  3. Batschelet E. 1981 Circular Statistics in Biology. London: Academic press

    Google Scholar 

  4. Billiar K. L., M. S. Sacks 1997 A method to quantify the fiber kinematics of planar tissues under biaxial stretch. J. Biomech. 30:753–756

    Article  PubMed  CAS  Google Scholar 

  5. Billiar K. L., M. S. Sacks 2000 Biaxial mechanical properties of the natural and glutaraldehyde treated aortic valve cusp—Part I: experimental results. J. Biomech. Eng. 122:23–30

    Article  PubMed  CAS  Google Scholar 

  6. Bonifasi-Lista C., S. P. Lake, M. S. Small, J. A. Weiss 2005 Viscoelastic properties of the human medial collateral ligament under longitudinal, transverse and shear loading. J. Orthop. Res. 23:67–76

    Article  PubMed  Google Scholar 

  7. Brightman A. O., B. P. Rajwa, J. E. Sturgis, M. E. McCallister, J. P. Robinson, S. L. Voytik-Harbin 2000 Time-lapse confocal reflection microscopy of collagen fibrillogenesis and extracellular matrix assembly in vitro. Biopolymers 54:222–234

    Article  PubMed  CAS  Google Scholar 

  8. Buck R. C. 1980 Reorientation response of cells to repeated stretch and recoil of the substratum. Exp. Cell. Res. 127:470–474

    Article  PubMed  CAS  Google Scholar 

  9. Carlsson A. S., C. F. Gentz 1980 Mechanical loosening of the femoral head prosthesis in the Charnley total hip arthroplasty. Clin. Orthop. Relat. Res. 147:262–270

    PubMed  Google Scholar 

  10. Chahine N. O., C. C. Wang, C. T. Hung, G. A. Ateshian 2004 Anisotropic strain-dependent material properties of bovine articular cartilage in the transitional range from tension to compression. J. Biomech. 37:1251–1261

    Article  PubMed  Google Scholar 

  11. Chandran P. L., V. H. Barocas 2006 Affine versus non-affine fibril kinematics in collagen networks: theoretical studies of network behavior. J. Biomech. Eng. 128:259–270

    Article  PubMed  Google Scholar 

  12. Costa K. D., Holmes J. W., McCulloch A. D. 2001 Modelling cardiac mechanical properties in three dimensions. Phil. Trans. R. Soc. Lond. A 359:1233–1250

    Article  Google Scholar 

  13. Costa K. D., E. J. Lee, J. W. Holmes 2003 Creating alignment and anisotropy in engineered heart tissue: role of boundary conditions in a model three-dimensional culture system. Tissue Eng. 9:567–577

    Article  PubMed  Google Scholar 

  14. Eastwood M., V. C. Mudera, D. A. McGrouther, R. A. Brown 1998 Effect of precise mechanical loading on fibroblast populated collagen lattices: morphological changes. Cell. Motil. Cytoskel. 40:13–21

    Article  CAS  Google Scholar 

  15. Enever P. A., D. I. Shreiber, R. T. Tranquillo 2002 A novel implantable collagen gel assay for fibroblast traction and proliferation during wound healing. J. Surg. Res. 105:160–172

    Article  PubMed  CAS  Google Scholar 

  16. Holmes J. W., T. K. Borg, J. W. Covell 2005 Structure and mechanics of healing myocardial infarcts. Annu. Rev. Biomed. Eng. 7:223–253

    Article  PubMed  CAS  Google Scholar 

  17. Ingber D. E. 2005 Mechanical control of tissue growth: function follows form. Proc. Natl. Acad. Sci. USA 102:11571–11572

    Article  PubMed  CAS  Google Scholar 

  18. Karlon W. J., P. P. Hsu, S. Li, S. Chien, A. D. McCulloch, J. H. Omens 1999 Measurement of orientation and distribution of cellular alignment and cytoskeletal organization. Ann. Biomed. Eng. 27:712–720

    Article  PubMed  CAS  Google Scholar 

  19. Knezevic V., A. J. Sim, T. K. Borg, J. W. Holmes 2002 Isotonic biaxial loading of fibroblast-populated collagen gels: a versatile, low-cost system for the study of mechanobiology. Biomech. Model Mechanobiol. 1:59–67

    Article  PubMed  CAS  Google Scholar 

  20. Lanyon L. E. 1974 Experimental support for the trajectorial theory of bone structure. J. Bone Joint Surg. Br. 56:160–166

    PubMed  CAS  Google Scholar 

  21. Loesberg W. A., X. F. Walboomers, J. J. van Loon, J. A. Jansen 2005 The effect of combined cyclic mechanical stretching and microgrooved surface topography on the behavior of fibroblasts. J. Biomed. Mater. Res. A 75:723–732

    PubMed  CAS  Google Scholar 

  22. Lynch H. A., W. Johannessen, J. P. Wu, A. Jawa, D. M. Elliott 2003 Effect of fiber orientation and strain rate on the nonlinear uniaxial tensile material properties of tendon. J. Biomech. Eng. 125:726–731

    Article  PubMed  Google Scholar 

  23. Manwaring M. E., J. F. Walsh, P. A. Tresco 2004 Contact guidance induced organization of extracellular matrix. Biomaterials 25:3631–3638

    Article  PubMed  CAS  Google Scholar 

  24. Mudera V. C., R. Pleass, M. Eastwood, R. Tarnuzzer, G. Schultz, P. Khaw, D. A. McGrouther, R. A. Brown 2000 Molecular responses of human dermal fibroblasts to dual cues: contact guidance and mechanical load. Cell Motil. Cytoskel. 45:1–9

    Article  CAS  Google Scholar 

  25. Sacks M. S. 1999 A method for planar biaxial mechanical testing that includes in-plane shear. J. Biomech. Eng. 121:551–555

    Article  PubMed  CAS  Google Scholar 

  26. Sarber R., B. Hull, C. Merrill, T. Soranno, E. Bell 1981 Regulation of proliferation of fibroblasts of low and high population doubling levels grown in collagen lattices. Mech. Ageing Dev. 17:107–117

    Article  PubMed  CAS  Google Scholar 

  27. Scheffe H. 1953 A method for judging all contrasts in the analysis of variance. Biometrika 40:87–104

    Google Scholar 

  28. Shieh S. J., J. P. Vacanti 2005 State-of-the-art tissue engineering: from tissue engineering to organ building. Surgery 137:1–7

    Article  PubMed  Google Scholar 

  29. Sipkema P., P. J. van der Linden, N. Westerhof, F. C. Yin 2003 Effect of cyclic axial stretch of rat arteries on endothelial cytoskeletal morphology and vascular reactivity. J. Biomech. 36:653–659

    Article  PubMed  Google Scholar 

  30. Terracio L., B. Miller, T. K. Borg 1988 Effects of cyclic mechanical stimulation of the cellular components of the heart: in vitro. In vitro Cell Dev. Biol. 24:53–58

    Article  PubMed  CAS  Google Scholar 

  31. Thomopoulos S., G. M. Fomovsky, P. L. Chandran, J. W. Holmes 2007 Collagen fiber alignment does not explain mechanical anisotropy in fibroblast populated collagen gels. J. Biomech. Eng. 129:642–650

    Article  PubMed  Google Scholar 

  32. Thomopoulos S., G. M. Fomovsky, J. W. Holmes 2005 The development of structural and mechanical anisotropy in fibroblast populated collagen gels. J. Biomech. Eng. 127:742–750

    Article  PubMed  Google Scholar 

  33. Tranquillo R. T. 1999 Self-organization of tissue-equivalents: the nature and role of contact guidance. Biochem. Soc. Symp. 65:27–42

    PubMed  CAS  Google Scholar 

  34. Wang J. H., E. S. Grood 2000 The strain magnitude and contact guidance determine orientation response of fibroblasts to cyclic substrate strains. Connect. Tissue Res. 41:29–36

    Article  PubMed  CAS  Google Scholar 

  35. Wang H., W. Ip, R. Boissy, E. S. Grood 1995 Cell orientation response to cyclically deformed substrates: experimental validation of a cell model. J. Biomech. 28:1543–1552

    Article  PubMed  CAS  Google Scholar 

  36. Wolff J. 1892 Das Gasetz der Transformation der Knochen. Berlin: Hirchwild

    Google Scholar 

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Acknowledgments

The authors thank Tony Ding for assistance with cell alignment analysis, Brian Wosnitzer for contributing to the collagen alignment measurements, Mitun Ranka for cell proliferation measurements, Dr. Preethi Chandran for assistance with non-affine modeling and Dr. Stavros Thomopoulos for providing data from viscoelastic creep experiments. Financial support from the Whitaker Foundation (RG 01-0160, KDC) and NIH/NHLBI (R01 HL-075639, JWH) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Anesthesiology, Yale University, New Haven, CT, USA

    Eun Jung Lee

  2. Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA

    Jeffrey W. Holmes

  3. Department of Biomedical Engineering, Columbia University in the City of New York, 1210 Amsterdam Avenue, mc 8904, New York, NY, 10027, USA

    Kevin D. Costa

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  1. Eun Jung Lee
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  2. Jeffrey W. Holmes
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  3. Kevin D. Costa
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Correspondence to Kevin D. Costa.

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Lee, E.J., Holmes, J.W. & Costa, K.D. Remodeling of Engineered Tissue Anisotropy in Response to Altered Loading Conditions. Ann Biomed Eng 36, 1322–1334 (2008). https://doi.org/10.1007/s10439-008-9509-9

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  • DOI: https://doi.org/10.1007/s10439-008-9509-9

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