Skip to main content
Log in

A Linear, Biphasic Model Incorporating a Brinkman Term to Describe the Mechanics of Cell-Seeded Collagen Hydrogels

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Protein-based hydrogels are commonly used as in vitro models of native tissues because they can mimic specific aspects of the three-dimensional extracellular matrix present in vivo. Bulk mechanical stimulation is often applied to these gels to determine the response of embedded cells to biomechanical factors such as stress and strain. This study develops and applies a linear, biphasic formulation of hydrogel mechanics that includes a Brinkman term to account for viscous effects. The model is used to predict fluid pressure, relative velocity, and estimated shear stress exerted on cells seeded within a cyclically strained collagen hydrogel with and without imposed cross flow. The model was validated using a confined compression creep test of a cardiac fibroblast-seeded collagen type I hydrogel, and the effect of the added Brinkman term was assessed. The model indicated that the effects of strain and interstitial fluid flow are strongly interdependent in the collagen hydrogel. Our results suggest that the contribution of the Brinkman term is greater in protein hydrogels than in native tissues, and that studies that apply cyclic strain to cell-seeded hydrogels should account for the induced interstitial fluid flow. This study, therefore, has relevance to the increasing number of studies that examine cellular responses to mechanical stresses using in vitro hydrogel models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  1. Allen, T. D., and S. T. Schor. The contraction of collagen matrices by dermal fibroblasts. J. Ultrastruct. Res. 83:205–219, 1983.

    Article  PubMed  CAS  Google Scholar 

  2. Ateshian, G. A., H. Wang, and W. M. Lai. The role of interstitial fluid pressurization and surface porosities on the boundary friction of articular cartilage. J. Tribol. ASME 120:241–251, 1998.

    Article  Google Scholar 

  3. Bell, E., B. Evarsson, 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. 76:1274–1278, 1979.

    Article  PubMed  CAS  Google Scholar 

  4. Bowen, R. Theory of mixtures. In: Continuum Physics, Vol. 3, edited by A. E. Eringen. New York, NY: Academic Press, 1976, pp. 1–127.

    Google Scholar 

  5. Breuls, R. G. M., B. G. Sengers, C. W. J. Oomens, C. V. C. Bouten, and F. P. T. Baaijens. Predicting local cell deformations in engineered tissue constructs: a multilevel finite element approach. J. Biomech. Eng. 124(2):198–208, 2002.

    Article  PubMed  Google Scholar 

  6. Chan, B., P. S. Donzelli, and R. L. Spilker. A mixed-penalty biphasic finite element formulation incorporating viscous fluids and material interfaces. Ann. Biomed. Eng. 28:589–597, 2000.

    Article  PubMed  CAS  Google Scholar 

  7. Chen, X., and M. Sarntinoranont. Biphasic finite element model of solute transport for direct infusion into nervous tissue. Ann. Biomed Eng. 35(12):2145–2158, 2007.

    Article  PubMed  Google Scholar 

  8. Chevallay, B., and D. Herbage. Collagen-based biomaterials as 3D scaffold for cell cultures: applications for tissue engineering and gene therapy. Med. Biol. Eng. Comput. 38:211–218, 2000.

    Article  PubMed  CAS  Google Scholar 

  9. Cummings, C. L., D. Gawlitta, R. M. Nerem, and J. P. Stegemann. Properties of engineered vascular constructs made from collagen, fibrin, and collagen–fibrin mixtures. Biomaterials 25(17):3699–3706, 2004.

    Article  PubMed  CAS  Google Scholar 

  10. Freed, L. E. Advanced tools for tissue engineering: scaffolds, bioreactors, and signaling. Tissue Eng. 12(12):3285–3305, 2006.

    Article  PubMed  CAS  Google Scholar 

  11. Galie, P. A., and J. P. Stegemann. Simultaneous application of interstitial flow and cyclic mechanical strain to a 3D cell-seeded hydrogel. Tissue Eng. C 17(5):527–536, 2011.

    Article  CAS  Google Scholar 

  12. Galie, P. A., M. V. Westfall, and J. P. Stegemann. Reduced serum content and increased matrix stiffness promote the cardiac myofibroblast transition in 3D collagen matrices. Cardiovasc. Pathol. 2011 [Epub ahead of print].

  13. Ghosh, K., et al. Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties. Biomaterials 28(4):671–679, 2007.

    Article  PubMed  CAS  Google Scholar 

  14. Grinnell, F. Fibroblast biology in three-dimensional collagen matrices. Trends Cell Biol. 13(5):264–269, 2003.

    Article  PubMed  CAS  Google Scholar 

  15. Gudi, S. R. P., A. A. Lee, C. B. Clark, and J. A. Frangos. Equibiaxial strain and strain rate stimulate early activation of G proteins in cardiac fibroblasts. Am. J. Physiol. Cell Physiol. 274(5):C1424–C1428, 1998.

    CAS  Google Scholar 

  16. Guilak, F., and V. C. Mow. The mechanical environment of the chondrocyte: a biphasic finite element model of cell–matrix interactions in articular cartilage. J. Biomech. 33(12):1663–1673, 2000.

    Article  PubMed  CAS  Google Scholar 

  17. Holmes, M. H. Finite deformation theory of soft tissue: analysis of a mixture model in uniaxial compression. J. Biomech. Eng. 108:372–381, 1986.

    Article  PubMed  CAS  Google Scholar 

  18. Hou, J. S., M. H. Holmes, W. M. Lai, and V. C. Mow. Boundary conditions at the cartilage-synovial fluid interface for joint lubrication and theoretical verifications. J. Biomech. Eng. 111:78–87, 1989.

    Article  PubMed  CAS  Google Scholar 

  19. Kenyon, D. E. The theory of an incompressible solid–fluid mixture. Arch. Ration. Mech. Anal. 62:131–147, 1976.

    Google Scholar 

  20. Kisiday, J., M. Jin, B. Kurz, et al. Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair. PNAS 99(15):9996–10001, 2002.

    Article  PubMed  CAS  Google Scholar 

  21. Mak, A. K., W. M. Lai, and V. C. Mow. Biphasic indentation of articular cartilage—I. Theoretical analysis. J. Biomech. 20(7):703–714, 1987.

    Article  PubMed  CAS  Google Scholar 

  22. McGuire, S., D. Zaharoff, and F. Yuan. Nonlinear dependence of hydraulic conductivity on tissue deformation during intratumoral infusion. Ann. Biomed Eng. 34(7):1173–1181, 2006.

    Article  PubMed  Google Scholar 

  23. 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. 102:73–84, 1980.

    Article  PubMed  CAS  Google Scholar 

  24. O’Brien, F. J., B. A. Harley, M. A. Waller, I. V. Yannas, L. J. Gibson, and P. J. Prendergast. The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering. Technol. Health Care 15:3–17, 2007.

    PubMed  Google Scholar 

  25. Ramanujan, S., A. Pluen, T. D. McKee, E. B. Brown, Y. Boucher, and R. K. Jain. Diffusion and convection in collagen gels: implications for transport in the tumor interstitium. Biophys. J. 83:1650–1660, 2002.

    Article  PubMed  CAS  Google Scholar 

  26. Slomka, N., S. Or-Tzadikario, D. Sassun, and A. Gefen. Membrane-stretch-induced cell death in deep tissue injury: computer model studies. Cell. Mol. Bioeng. 2(1):118–132, 2009.

    Article  CAS  Google Scholar 

  27. Spilker, R. L., J.-K. Suh, and V. C. Mow. A finite element formulation of the nonlinear biphasic model for articular cartilage and hydrated soft tissues including strain-dependent permeability. In: Computational Methods in Bioengineering, edited by R. L. Spilker, and B. R. Simon. New York: ASME, 1982, pp. 81–92.

    Google Scholar 

  28. Stegemann, J. P., H. Hong, and R. M. Nerem. Mechanical, biochemical, and extracellular matrix effects on vascular smooth muscle cell phenotype. J. Appl. Physiol. 98:2321–2327, 2005.

    Article  PubMed  Google Scholar 

  29. Stegemann, J. P., and R. M. Nerem. Phenotype modulation in vascular tissue engineering using biochemical and mechanical stimulation. Ann. Biomed. Eng. 31(4):391–402, 2003.

    Article  PubMed  Google Scholar 

  30. Stops, A. J. F., and L. A. McMahon. A finite element prediction of strain on cells in a highly porous collagen-glycosaminoglycan scaffold. J. Biomech. Eng. 130(6):100–111, 2008.

    Article  Google Scholar 

  31. Stylianopoulos, T. Volume-averaging theory for the study of the mechanics of collagen networks. Comput. Methods Appl. Mech. Eng. 196(31–32):2981–2990, 2007.

    Article  Google Scholar 

  32. Wang, D. M., and J. M. Tarbell. Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle Cells. J. Biomech. Eng. 117(3):358–364, 1995.

    Article  PubMed  CAS  Google Scholar 

  33. Weinand, C., I. Pomerantseva, C. M. Neville, R. Gupta, E. Weinberg, I. Madisch, F. Shapiro, H. Abukawa, M. J. Troulis, and J. P. Vacanti. Hydrogel-β-TCP scaffolds and stem cells for tissue engineering bone. Bone 38(4):555–563, 2006.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by the Microfluidics in Biomedical Sciences Training Program at the University of Michigan, sponsored by the National Institute of Biomedical Imaging and Bioengineering.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jan P. Stegemann.

Additional information

Associate Editor Konstantinos Konstantopoulos oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galie, P.A., Spilker, R.L. & Stegemann, J.P. A Linear, Biphasic Model Incorporating a Brinkman Term to Describe the Mechanics of Cell-Seeded Collagen Hydrogels. Ann Biomed Eng 39, 2767–2779 (2011). https://doi.org/10.1007/s10439-011-0371-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-011-0371-9

Keywords

Navigation