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Swelling of Collagen-Hyaluronic Acid Co-Gels: An In Vitro Residual Stress Model

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Abstract

Tissue-equivalents (TEs), simple model tissues with tunable properties, have been used to explore many features of biological soft tissues. Absent in most formulations however, is the residual stress that arises due to interactions among components with different unloaded levels of stress, which has an important functional role in many biological tissues. To create a pre-stressed model system, co-gels were fabricated from a combination of hyaluronic acid (HA) and reconstituted Type-I collagen (Col). When placed in solutions of varying osmolarity, HA-Col co-gels swell as the HA imbibes water, which in turn stretches (and stresses) the collagen network. In this way, co-gels with residual stress (i.e., collagen fibers in tension and HA in compression) were fabricated. When the three gel types tested here were immersed in hypotonic solutions, pure HA gels swelled the most, followed by HA-Col co-gels; no swelling was observed in pure collagen gels. The greatest swelling rates and swelling ratios occurred in the lowest salt concentration solutions. Tension on the collagen component of HA-Col co-gels was calculated from a stress balance and increased nonlinearly as swelling increased. The swelling experiment results were in good agreement with the stress predicted by a fibril network + non-fibrillar interstitial matrix computational model.

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References

  1. Albro, M. B., N. O. Chahine, M. Caligaris, V. I. Wei, K. W. Ng, C. T. Hung, and G. A. Ateshian. NIH Public Access. 129:503–510, 2010.

  2. Alexander, A., and R. B. Donoff. The glycosaminoglycans of open wounds. J. Surg. Res. 29(5):422–429, 1980.

    Article  CAS  PubMed  Google Scholar 

  3. Alexander-Katz, A., and R. R. Netz. Dynamics and instabilities of collapsed polymers in shear flow. Macromolecules 41:3363–3374, 2008.

    Article  CAS  Google Scholar 

  4. Anandagoda, N., D. G. Ezra, U. Cheema, M. Bailly, and R. A. Brown. Hyaluronan hydration generates three-dimensional meso-scale structure in engineered collagen tissues. J. R. Soc. Interface 9:2680–2687, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Armon, S., E. Efrati, R. Kupferman, and E. Sharon. Geometry and mechanics in the opening of chiral seed pods. Science 333:1726–1729, 2011.

    Article  CAS  PubMed  Google Scholar 

  6. Ateshian, G. A., S. Maas, and J. A. Weiss. Multiphasic finite element framework for modeling hydrated mixtures with multiple neutral and charged solutes. J. Biomech. Eng. 135:111001, 2013.

    Article  PubMed  Google Scholar 

  7. Barocas, V. H., and R. T. Tranquillo. 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, 1997.

    Article  CAS  PubMed  Google Scholar 

  8. Bell, E., B. Ivarsson, and C. Merrill. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl. Acad. Sci. USA 76:1274–1278, 1979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Choh, S. Y., D. Cross, and C. Wang. Facile synthesis and characterization of disulfide-cross-linked hyaluronic acid hydrogels for protein delivery and cell encapsulation. Biomacromolecules 12:1126–1136, 2011.

    Article  CAS  PubMed  Google Scholar 

  10. Donnan, F. G. The theory of membrane equilibria. Chem. Rev. 1:73–90, 1924.

    Article  CAS  Google Scholar 

  11. Frey, H., N. Schroeder, T. Manon-Jensen, R. V. Iozzo, and L. Schaefer. Biological interplay between proteoglycans and their innate immune receptors in inflammation. FEBS J. 280:2165–2179, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fyhrie, D. P., and J. R. Barone. Polymer dynamics as a mechanistic model for the flow-independent viscoelasticity of cartilage. J. Biomech. Eng. 125:578–584, 2003.

    Article  CAS  PubMed  Google Scholar 

  13. Greco, R. M., J. A. Iocono, and H. P. Ehrlich. Hyaluronic acid stimulates human fibroblast proliferation within a collagen matrix. J. Cell. Physiol. 177:465–473, 1998.

    Article  CAS  PubMed  Google Scholar 

  14. Han, E., S. S. Chen, S. M. Klisch, and R. L. Sah. Contribution of proteoglycan osmotic swelling pressure to the compressive properties of articular cartilage. Biophys. J. 101:916–924, 2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hargittai, I., and M. Hargittai. Molecular structure of hyaluronan: an introduction. Struct. Chem. 19:697–717, 2008.

    Article  CAS  Google Scholar 

  16. Jhun, C.-S., M. C. Evans, V. H. Barocas, and R. T. Tranquillo. Planar biaxial mechanical behavior of bioartificial tissues possessing prescribed fiber alignment. J. Biomech. Eng. 131:081006, 2009.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kreger, S. T., and S. L. Voytik-Harbin. Hyaluronan concentration within a 3D collagen matrix modulates matrix viscoelasticity, but not fibroblast response. Matrix Biol. 28:336–346, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lai, V. K., C. R. Frey, A. M. Kerandi, S. P. Lake, R. T. Tranquillo, and V. H. Barocas. Microstructural and mechanical differences between digested collagen-fibrin co-gels and pure collagen and fibrin gels. Acta Biomater. 8:4031–4042, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lai, V. K., S. P. Lake, C. R. Frey, R. T. Tranquillo, and V. H. Barocas. Mechanical behavior of collagen-fibrin co-gels reflects transition from series to parallel interactions with increasing collagen content. J. Biomech. Eng. 134:011004, 2012.

    Article  PubMed  Google Scholar 

  20. Lake, S. P., and V. H. Barocas. Mechanical and structural contribution of non-fibrillar matrix in uniaxial tension: a collagen-agarose co-gel model. Ann. Biomed. Eng. 39:1891–1903, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lake, S. P., M. F. Hadi, V. K. Lai, and V. H. Barocas. Mechanics of a fiber network within a non-fibrillar matrix: model and comparison with collagen-agarose co-gels. Ann. Biomed. Eng. 40:2111–2121, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lake, S. P., E. S. Hald, and V. H. Barocas. Collagen-agarose co-gels as a model for collagen-matrix interaction in soft tissues subjected to indentation. J. Biomed. Mater. Res. A 99:507–515, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lanir, Y. Osmotic swelling and residual stress in cardiovascular tissues. J. Biomech. 45:780–789, 2012.

    Article  PubMed  Google Scholar 

  24. Laurent, T. C. The Chemistry, Biology and Medical Applications of Hyaluronan and Its Derivatives. London: Portland Press Limited, p. 368, 1998.

    Google Scholar 

  25. Luo, Y., K. R. Kirker, and G. D. Prestwich. Cross-linked hyaluronic acid hydrogel films: new biomaterials for drug delivery. J. Control. Release 69:169–184, 2000.

    Article  CAS  PubMed  Google Scholar 

  26. Marquez, J. P., G. M. Genin, K. M. Pryse, and E. L. Elson. Cellular and matrix contributions to tissue construct stiffness increase with cellular concentration. Ann. Biomed. Eng. 34:1475–1482, 2006.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Michalek, A. J., M. G. Gardner-Morse, and J. C. Iatridis. Large residual strains are present in the intervertebral disc annulus fibrosus in the unloaded state. J. Biomech. 45:1227–1231, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moon, A. G., and R. T. Tranquillo. Fibroblast-populated collagen microsphere assay of cell traction force. 1. Continuum model. Aiche J. 39:163–177, 1993.

    Article  CAS  Google Scholar 

  29. Mow, V. C., M. H. Holmes, and W. M. Lai. Fluid transport and mechanical properties of articular cartilage: a review. J. Biomech. 17:377–394, 1984.

    Article  CAS  PubMed  Google Scholar 

  30. Nardinocchi, P., and M. Pezzulla. Curled actuated shapes of ionic polymer metal composites strips. J. Appl. Phys. 113:224906, 2013.

    Article  Google Scholar 

  31. Nelson, D. Experimental methods for determining residual stresses and strains in various biological structures. Exp. Mech. 54:695–708, 2014.

    Article  Google Scholar 

  32. Pan, Y., and Z. Zhong. A nonlinear constitutive model of unidirectional natural fiber reinforced composites considering moisture absorption. J. Mech. Phys. Solids 69:132–142, 2014.

    Article  Google Scholar 

  33. Park, S.-N., H. J. Lee, K. H. Lee, and H. Suh. Biological characterization of EDC-crosslinked collagen-hyaluronic acid matrix in dermal tissue restoration. Biomaterials 24:1631–1641, 2003.

    Article  CAS  PubMed  Google Scholar 

  34. Roeder, B. A., K. Kokini, J. E. Sturgis, J. P. Robinson, and S. L. Voytik-Harbin. Tensile mechanical properties of three-dimensional type I collagen extracellular matrices with varied microstructure. J. Biomech. Eng. 124:214, 2002.

    Article  PubMed  Google Scholar 

  35. Ruberti, J. W., and J. B. Sokoloff. Theory of the short time mechanical relaxation in articular cartilage. J. Biomech. Eng. 133:104504, 2011.

    Article  CAS  PubMed  Google Scholar 

  36. Sander, E., A. T. Stylianopoulos, T. Tranquillo, and V. H. Barocas. Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels. Proc. Natl. Acad. Sci. USA 106:17675–17680, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Segura, T., B. C. Anderson, P. H. Chung, R. E. Webber, K. R. Shull, and L. D. Shea. Crosslinked hyaluronic acid hydrogels: a strategy to functionalize and pattern. Biomaterials 26:359–371, 2005.

    Article  CAS  PubMed  Google Scholar 

  38. Taber, L. A., and J. D. Humphrey. Stress-modulated growth, residual stress, and vascular heterogeneity. J. Biomech. Eng. 123:528–535, 2001.

    Article  CAS  PubMed  Google Scholar 

  39. Walters, B. D., and J. P. Stegemann. Strategies for directing the structure and function of three-dimensional collagen biomaterials across length scales. Acta Biomater. 10:1488–1501, 2014.

    Article  CAS  PubMed  Google Scholar 

  40. Weiss, J. A. Computational modeling of ligament mechanics. Crit. Rev. Biomed. Eng. 29:303–371, 2001.

    Article  CAS  PubMed  Google Scholar 

  41. Zheng Shu, X., Y. Liu, F. S. Palumbo, Y. Luo, and G. D. Prestwich. In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials 25:1339–1348, 2004.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institute of Health (RO1 EB005813), and by a resources grant from the Minnesota Supercomputing Institute. There are no conflicts of interest.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Minnesota, Duluth, MN, USA

    Victor K. Lai

  2. Department of Biomedical Engineering, University of Minnesota – Twin Cities, 7-105 Nils Hasselmo Hall, 312 Church St. SE, Minneapolis, MN, 55455, USA

    David S. Nedrelow, Bumjun Kim, Emily M. Weiss, Robert T. Tranquillo & Victor H. Barocas

  3. Department of Mechanical Engineering & Materials Science, Washington University in St. Louis, St. Louis, MO, USA

    Spencer P. Lake

  4. Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, USA

    Robert T. Tranquillo

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  1. Victor K. Lai
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Correspondence to Victor H. Barocas.

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Associate Editor Kent Leach oversaw the review of this article.

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Lai, V.K., Nedrelow, D.S., Lake, S.P. et al. Swelling of Collagen-Hyaluronic Acid Co-Gels: An In Vitro Residual Stress Model. Ann Biomed Eng 44, 2984–2993 (2016). https://doi.org/10.1007/s10439-016-1636-0

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