LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Publisher: Springer
Languages: English
Types: Article
Subjects:
In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. \ud \ud In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (i) differential interactions between cells and the supporting scaffold and their associated ECM, (ii) scaffold degradation, and (iii) mechanotransduction-regulated cell proliferation and ECM deposition.\ud \ud Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from µCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of engineered tissue constructs and their suitability for implantation in vivo.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • T. Adachi, Y. Osako, M. Tanaka, M. Hojo, and S.J. Hollister. Framework for optimal design of porous scaffold microstructure by compututational simulation of bone regeneration. Biomat., 27: 3964-3972, 2006.
    • M. Ahearne, S.L. Wilson, K-K Liu, S. Rauz, A.J. El Haj, and Y. Yang. Influence of cell and collagen concentration on the cell-matrix mechanical relationship in a corneal stroma wound healing model. Exp. Eye Res., 91:584-591, 2010.
    • R.P. Araujo and D.L.S McElwain. A mixture theory for the genesis of residual stresses in growing tissues i: A general formulation. SIAM J. of App. Math., 65(4):1261-1284, 2005.
    • A. Bakker, J. Klein-Nulend, and E. Burger. Shear stress inhibits while disuse promotes osteocyte apoptosis. Biochem. Biophys. Res. Comm., 320:1163-1168, 2004a.
    • A. Bakker, J. Klein-Nulend, and E. Burger. Shear stress inhibits while disuse promotes osteocyte apoptosis. Biochem. Biophys. Res. Commun., 320(4):1163-1168, 2004b.
    • C.J.W. Breward, H.M. Byrne, and C.E. Lewis. The role of cell-cell interactions in a two-phase model for avascular tumour growth. J. Math. Biol., 45:125-152, 2002.
    • J.A. Burdick and R.L. Mauck, editors. Biomaterials for Tissue Engineering Applications: A Review of the Past and Future Trends. Springer, Wien, 2010.
    • D.P. Byrne, D. Lacroix, J.A. Planell, D.J. Kelly, and P.J. Prendergast. Simulation of tissue differentiation in a scaffold as a function of porosity, Young's modulus and dissolution rate: application of mechanobiological models in tissue engineering. Biomat., 28(36):5544-5554, 2007.
    • H.M. Byrne and L. Preziosi. Modelling solid tumour growth using the theory of mixtures. Math. Med. Biol., 20(4):341-366, 2003.
    • S.H. Cartmell and A.J. El Haj. Mechanical bioreactors for tissue engineering. In J. Chaudhuri and M. Al-Rubeai, editors, Bioreactors for tissue engineering: Principles, Design and Operation, chapter 8, pages 193-209. Springer, Dordrecht, The Netherlands, 2005.
    • M.A.J. Chaplain, L. Graziano, and L. Preziosi. Mathematical modelling of the loss of tissue compression responsiveness and its role in solid tumour development. Math. Med. Biol., 23(3):197, 2006.
    • S.C. Cowin. Tissue growth and remodeling. Ann. Rev. of Biomed. Eng., 6(1):77-107, 2004.
    • S.C. Cowin. How is a tissue built? J. Biomech. Eng., 122:553, 2000.
    • A. Curtis and M. Riehle. Tissue engineering: the biophysical background. Phys. in MEd. and Biol, 46:47-65, 2001.
    • D.A. Drew and L.A. Segel. Averaged equations for two-phase flows. Studies in Appl. Math., 50: 205-231, 1971.
    • A.J. El Haj, S.L. Minter, S.C. Rawlinson, R. Suswillo, and L.E. Lanyon. Cellular responses to mechanical loading in vitro. J. Bone and Min. Res., 5(9):923-32, 1990.
    • S.J. Franks and J.R. King. Interactions between a uniformly proliferating tumour and its surroundings: uniform material properties. Math. Med. Biol., 20:47-89, 2003.
    • L.E. Freed and G. Vunjak-Novakovic. Culture of organized cell communities. Advanced Drug Delivery Rev., 33:15-30, 1998.
    • L.E. Freed, G. Vunjak-Novakovic, R.J. Biron, D.B. Eagles, D.C. Lesnoy, S.K. Barlow, and R. Langer. Biodegradable polymer scaffolds for tissue engineering. Nat. Biotech., 12(7):689- 693, 1994.
    • Y.C. Fung. What are residual stresses doing in our blood vesels? Ann. Biomed. Eng., 19:237-249, 1991.
    • M.A. Haider, J.E. Olander, R.F. Arnold, D.R. Marous, A.J. McLamb, K.C. Thompson, W.R. Woodruff, and J.M. Haugh. A phenomenological mixture model for biosynthesis and linking of cartilage extracellular matrix in scaffolds seeded with chondrocytes. Biomech. Model. Mechanobiol., pages 1-10, 2010. ISSN 1617-7959.
    • Y. Han, S.C. Cowin, M.B. Schaffler, and S. Weinbaaum. Mechanotransduction and strain amplification in osteocyte cell processes. Proc. Nat. Acad. of Sci., 101(47):16689-16694, 2004.
    • G.A. Holzapfel and R.W. Ogden. Mechanics of biological tissue. Springer-Verlag, Berlin, 2006.
    • D.J. Kelly and P.J. Prendergast. Effect of a degraded core on the mechanical behaviour of tissueengineered cartilage constructs: a poro-elastic finite element analysis. Med. Biol. Eng. and Comp., 42:9-13, 2003.
    • J. Klein-Nulend, J. Roelofsen, J.G. Sterck, C.M. Semeins, and E.H. Burger. Mechanical loading stimulates the release of transforming growth factor-beta activity by cultured mouse calvariae and periosteal cells. Journal of Cell Physiology, 163(1):115-119, 1995.
    • Wu L. and J. Ding. In vitro degradation of three-dimensional porous poly(d,l-lactide-co-glycolide) scaffolds for tissue engineering. Biomat., 25(27):5821-5830, 2004.
    • K.A. Landman and C.P. Please. Tumour dynamics and necrosis: Surface tension and stability. IMA J. of Math. Appl. in Med. and Biol., 18(2):131-158, 2001.
    • G. Lemon and J.R. King. Multiphase modelling of cell behaviour on artificial scaffolds: effects of nutrient depletion and spatially nonuniform porosity. Math. Med. Biol., 24(1):57, 2007.
    • G. Lemon, J.R King, H.M. Byrne, O.E. Jensen, and K. Shakesheff. Multiphase modelling of tissue growth using the theory of mixtures. J. Math. Biol., 52(2):571-594, 2006.
    • M.C. Lewis, B.D. Macarthur, J. Malda, G. Pettet, and C.P. Please. Heterogeneous proliferation within engineered cartilaginous tissue: the role of oxygen tension. Biotech. and Bioeng., 91(5): 607-15, 2005.
    • S.R. Lubkin and T. Jackson. Multiphase Mechanics of Capsule Formation in Tumors. J. Biomech. Eng., 124:237, 2002.
    • I. Martin, D. Wendt, and M. Heberer. The role of bioreactors in tissue engineering. Trends in Biotechn., 22(2):80-86, 2004.
    • J. Nikolovski and D.J. Mooney. Smooth muscle cell adhesion to tissue engineering scaffolds. Biomat., 21(20):2025-2032, 2000.
    • R.D. O'Dea, S.L. Waters, and H.M. Byrne. A two-fluid model for tissue growth within a dynamic flow environment. Eur. J. Appl. Math., 19(641):607-634, 2008.
    • R.D. O'Dea, S.L. Waters, and H.M. Byrne. A three phase model for tissue construct growth in a perfusion bioreactor. J. Math. Med. Biol., 27(2):95-127, 2010.
    • R.D. O'Dea, S.L. Waters, and H.M. Byrne. Modelling tissue growth in bioreactors: a review. In L. Geris, editor, Computational Modeling in Tissue Engineering. Springer-Verlag, 2012.
    • J.M. Osborne and J.P. Whiteley. A numerical method for the multiphase viscous flow equations. Comput. Methods Appl. Mech. Engrg., 199:3402-3417, 2010. doi:10.1016/j.cma.2010.07.011.
    • J.M. Osborne, R.D. ODea, J.P. Whiteley, H.M. Byrne, and S.L. Waters. The influence of bioreactor geometry and the mechanical environment on engineered tissues. J. Biomech. Eng., 132(5), 2010. doi: 10.1115/1.4001160.
    • L. Preziosi and A. Tosin. Multiphase and multiscale trends in cancer modelling. Math. Model. Nat. Phenom., 4(3):1-11, 2009. ISSN 0973-5348.
    • J. Roelofsen, J. Klein-Nulend, and E.H. Burger. Mechanical stimulation by intermittent hydrostatic compression promotes bone-specific gene expression in vitro. J. Biomech., 28(12):1493-1503, 1995.
    • T. Roose, P.A. Neti, L.L. Munn, Y. Boucher, and R.K. Jain. Solid stress generated by spheroid growth estimated using a poroelasticity model. Microvascular Res., 66:204-212, 2003.
    • J.A. Sanz-Herrera, J.M. Garc´ıa-Aznar, and M. Doblare´. On scaffold designing for bone regeneration: A computational multiscale approach. Acta Biomat., Online PrePrint, 2008.
    • J.D. Sipe. Tissue Engineering and Reparative Medicine. Ann. of the New York acad. of Sci., 961: 1-9, 2002.
    • R. Skalak, S. Zargaryan, R.K. Jain, P.A. Netti, and A. Hoger. Compatibility and the genesis of residual stress by volumetric growth. J. Math. Biol., 34:889-914, 1996.
    • JPG Urban. The chondrocyte: a cell under pressure. Rheumat., 33(10):901-908, 1994.
    • J. VonNeumann and R.D. Richtmyer. A method for the numerical calculation of hydrodynamic shocks. J. Appl. Phys., 21:232, 1950.
    • Q.G. Wang, B. Nguyen, C.R. Thomas, Z. Zhang, A.J. El Haj, and N.J. Kuiper. Molecular profiling of single cells in response to mechanical force: comparison of chondrocytes, chondrons and encapsulated chondrocytes. Biomat., 31(7):1619-1625, 2010.
    • D.J. Wilson, J.R. King, and H.M. Byrne. Modelling scaffold occupation by a growing, nutrient-rich tissue. Math. Models Methods Appl. Sci., 17:1721, 2007.
    • Y. Yang and AJ El Haj. Biodegradable scaffolds - delivery systems for cell therapies. Expert Opin. Biol. Ther., 6(5):485-498, 2006.
    • J. You, C.E. Yellowley, H.J. Donahue, Y. Zhang, Q. Chen, and C.R. Jacobs. Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. Journal of Biomechanical Engineering, 122:377-393, 2000.
    • L. You, S.C. Cowin, M.B. Schaffler, and S. Weinbaum. A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J. Biomech., 34(11):1375-86, 2001.
    • G. Yourek, A. Al-Hadlaq, R. Patel, S. McCormick, G.C. Reilly, and J.J. Mao. Nanophysical properties of living cells. In Michael A. Stroscio, Mitra Dutta, and Bin He, editors, Biological Nanostructures and Applications of Nanostructures in Biology, Bioelectric Engineering, pages 69-97. Springer US, 2004.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article