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Computational Approaches to Solving Equations Arising from Wound Healing

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Abstract

In the wound healing process, the cell movement associated with chemotaxis generally outweighs the movement associated with random motion, leading to advection-dominated mathematical models of wound healing. The equations in these models must be solved with care, but often inappropriate approaches are adopted. Two one-dimensional test problems arising from advection-dominated models of wound healing are solved using four algorithms—MATLAB’s inbuilt routine pdepe.m, the Numerical Algorithms Group routine d03pcf.f, and two finite volume methods. The first finite volume method is based on a first-order upwinding treatment of chemotaxis terms and the second on a flux limiting approach. The first test problem admits an analytic solution which can be used to validate the numerical results by analyzing two measures of the error for each method: the average absolute difference and a mass balance error. These criteria as well as the visual comparison between the numerical methods and the exact solution lead us to conclude that flux limiting is the best approach to solving advection-dominated wound healing problems numerically in one dimension. The second test problem is a coupled nonlinear three species model of wound healing angiogenesis. Measurement of the mass balance error for this test problem further confirms our hypothesis that flux limiting is the most appropriate method for solving advection-dominated governing equations in wound healing models. We also consider two two-dimensional test problems arising from wound healing, one that admits an analytic solution and a more complicated problem of blood vessels growth into a devascularized wound bed. The results from the two-dimensional test problems also demonstrate that the flux limiting treatment of advective terms is ideal for an advection-dominated problem.

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References

  • Anderson, A., Chaplain, M., 1998. Continuous and discrete mathematical models of tumor-induced angiogenesis. J. Bull. Math. Biol. 60(5), 857–899.

    Article  MATH  Google Scholar 

  • Ayello, E.A., Cuddigan, J.E., 2004. Conquer chronic wounds with wound bed preparation. Nurse Pract. 29(3), 8–25.

    Article  Google Scholar 

  • Balding, D., McElwain, D.L.S., 1985. A mathematical model of tumour-induced capillary growth. J. Theor. Biol. 114(1), 53–73.

    Article  Google Scholar 

  • Baliga, B.R., Patankar, S.V., 1980. A new finite-element formulation for convection-diffusion problems. Numer. Heat Transf. Part A: Appl. 3(4), 393–409.

    Google Scholar 

  • Berzins, M., Dew, P.M., Furzeland, R.M., 1989. Developing software for time-dependent problems using the method of lines and differential-algebraic integrators. Appl. Numer. Math. 5(5), 375–397.

    Article  MATH  Google Scholar 

  • Bray, D., 1992. Cell Movements, Garland, New York.

    Google Scholar 

  • Brown, P., Saad, Y., 1990. Hybrid Krylov methods for nonlinear equations. SIAM J. Sci. Stat. Comput. 11(3), 450–481.

    Article  MATH  MathSciNet  Google Scholar 

  • Byrne, H.M., Chaplain, M.A.J., 1996. Explicit solutions of a simplified model of capillary sprout growth during tumour angiogenesis. Appl. Math. Lett. 9(1), 69–74.

    Article  MATH  MathSciNet  Google Scholar 

  • Byrne, H.M., Chaplain, M.A.J., Evans, D.L., Hopkinson, I., 2000. Mathematical modelling of angiogenesis in wound healing: comparison of theory and experiment. J. Theor. Med. 2(3), 175–197.

    MATH  Google Scholar 

  • Celik, I., Hu, G., 2004. Single grid error estimation using error transport equation. J. Fluids Eng. 126, 778–790.

    Article  Google Scholar 

  • Chaplain, M.A.J., McDougall, S.R., Anderson, A.R.A., 2006. Mathematical modelling of tumour-induced angiogenesis. Annu. Rev. Biomed. Eng. 8, 233–257.

    Article  Google Scholar 

  • Cliff, W.J., 1963. Observations on healing tissue: a combined light and electron microscopic investigation. Philos. Trans. R. Soc. Lond. Ser. B, Biol. Sci. 246(733), 305–325.

    Article  Google Scholar 

  • Dalton, S., Whiting, C., Bailey, J., Mitchell, D., Tarlton, J., 2007. Mechanisms of chronic skin ulceration linking lactate, transforming growth factor beta, vascular endothelial growth factor, collagen remodeling, collagen stability, and defective angiogenesis. J. Invest. Dermatol. 127, 958–968.

    Article  Google Scholar 

  • Delay, F., Porel, G., Banton, O., 1998. An approach to transport in heterogeneous porous media using the truncated temporal moment equations: theory and numerical validation. Transp. Porous Media 32(2), 199–232.

    Article  MathSciNet  Google Scholar 

  • Desmouliére, A., Darby, I.A., Gabbiani, G., 2003. Normal and pathologic soft tissue remodeling: role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Labor. Invest. 83, 1689–1707.

    Article  Google Scholar 

  • Diegelmann, R.F., Evans, M.C., 2004. Wound healing: an overview of acute, fibrotic and delayed healing. Front. Biosci. 9, 283–289.

    Article  Google Scholar 

  • Ditkowski, A., Fibich, G., Gavish, N., 2007. Efficient solution of Ax(k)=b(k) using A-1. J. Sci. Comput. 32(1), 29–44.

    Article  MATH  MathSciNet  Google Scholar 

  • Finlayson, B.A., 1992. Numerical Methods for Problems with Moving Fronts. Ravenna Park Publishing, New York.

    Google Scholar 

  • Forsyth, P.A., Vetzal, K.R., 2002. Quadratic convergence of a penalty method for valuing American options. SIAM J. Sci. Comput. 23, 2096–2123.

    Article  MathSciNet  Google Scholar 

  • Gaffney, E.A., Pugh, K., Maini, P.K., Arnold, F., 2002. Investigating a simple model of cutaneous wound healing angiogenesis. J. Math. Biol. 45(4), 337–374.

    Article  MATH  MathSciNet  Google Scholar 

  • Garvie, M.R., 2007. Finite-difference schemes for reaction-diffusion equations modeling predator-prey interactions in MATLAB. Bull. Math. Biol. 69, 931–956.

    Article  MATH  MathSciNet  Google Scholar 

  • Gustafsson, K., 1991. Control theoretic techniques for stepsize selection in explicit Runge-Kutta methods. ACM Trans. Math. Softw. 17, 533–554.

    Article  MATH  MathSciNet  Google Scholar 

  • Harten, A., 1983. High resolution schemes for hyperbolic conservation laws. J. Comput. Phys. 49(3), 357–393.

    Article  MATH  MathSciNet  Google Scholar 

  • Hochbruck, M., Lubich, C., Selhofer, H., 1998. Exponential integrators for large systems of differential equations. SIAM J. Sci. Comput. 19(5), 1552–1574.

    Article  MATH  MathSciNet  Google Scholar 

  • Hundsdorfer, W., Verwer, J., 2003. Numerical Solution of Time-Dependent Advection–Diffusion Reaction Equations. Springer, Berlin.

    MATH  Google Scholar 

  • Kelley, C.T., 1995. SIAM Frontiers in Applied Mathematics, pp. 1–166. SIAM, Philadelphia.

    Google Scholar 

  • Kelly, C.E., Leek, R.D., Byrne, H.M., Cos, S.M., Harris, A.L., Lewis, C.E., 2002. Modelling macrophage infiltration into avascular tumours. J. Theor. Med. 4(1), 21–39.

    Article  MATH  Google Scholar 

  • Kolar, R.L., Werterink, J.J., 2000. A look back at 20 years of GWC-based shallow water models. In: Proceedings of the XIII International Conference on Computational Methods in Water Resources, Calgary, Alberta, Canada, pp. 899–906.

  • Kucharzewski, M., Slezak, A., Franek, A., 2003. Topical treatment of non-healing venous leg ulcers by cellulose membrane. Phlebologie 32, 147–151.

    Google Scholar 

  • Landman, K.A., Pettet, G.J., Newgreen, D.F., 2003. Mathematical models of cell colonization of uniformly growing domains. Bull. Math. Biol. 65(2), 235–262.

    Article  Google Scholar 

  • Lauffenburger, D., 1983. Measurement of phenomenological parameters for leukocyte motility and chemotaxis. Agents Actions Suppl. 12, 34–53.

    Google Scholar 

  • Mac Gabhann, F., Popel, A.S., 2005. Differential binding of VEGF isoforms to VEGF receptor 2 in the presence of neuropilin-1: a computational model. Am. J. Physiol. Heart Circ. Physiol. 288, 2851–2860.

    Article  Google Scholar 

  • Madzvamuse, A., Maini, P.K., 2007. Velocity-induced numerical solutions of reaction-diffusion systems on continuously growing domains. J. Comput. Phys. 225(1), 100–119.

    Article  MATH  MathSciNet  Google Scholar 

  • Madzvamuse, A., Wathen, A.J., Maini, P.K., 2003. A moving grid finite element method applied to a model biological pattern generator. J. Comput. Phys. 190(2), 478–500.

    Article  MATH  MathSciNet  Google Scholar 

  • Mallet, D.G., Turner, I.W., Pettet, G.J., 2004. Application of the control volume method to a mathematical model of cell migration. ANZIAM J. 45, C891–C904.

    MathSciNet  Google Scholar 

  • Martins, M.A., Valle, R.M., 2002. Error estimation and adaptivity for finite-volume methods on unstructured triangular meshes: elliptic heat transfer problems. Numer. Heat Transf. Part B 42(5), 461–483.

    Article  Google Scholar 

  • Moore, K., Ruge, F., Harding, K., 1997. T lymphocytes and the lack of activated macrophages in wound margin biopsies from chronic leg ulcers. Br. J. Dermatol. 137, 188–194.

    Article  Google Scholar 

  • Omar, A.A., Mavor, A.I.D., Jones, A.M., Homer-Vanniasinkam, S., 2004. Treatment of venous leg ulcers with dermagraft. Eur. J. Vasc. Endovasc. Surg. 27(6), 666–672.

    Article  Google Scholar 

  • Owen, M.R., Sherratt, J.A., 1997. Pattern formation and spatiotemporal irregularity in a model for macrophage-tumour interactions. J. Theor. Biol. 189(1), 63–80.

    Article  Google Scholar 

  • Panovska, J., Byrne, H.M., Maini, P.K., 2008. A theoretical study of the response of vascular tumours to different types of chemotherapy. Math. Comput. Model. 47, 560–579.

    Article  MATH  MathSciNet  Google Scholar 

  • Patankar, S.V., Millman, E.M., 1980. Numerical Heat Transfer and Fluid Flow, Hemisphere, Washington.

    MATH  Google Scholar 

  • Pettet, G.J., Byrne, H.M., McElwain, D.L.S., Norbury, J., 1996a. A model of wound-healing angiogenesis in soft tissue. Math. Biosci. 136(1), 35–63.

    Article  MATH  Google Scholar 

  • Pettet, G.J., Chaplain, M.A.J., McElwain, D.L.S., Byrne, H.M., 1996b. On the role of angiogenesis in wound healing. Proc. R. Soc. Lond. B 263(1376), 1487–1493.

    Article  Google Scholar 

  • Pooley, D.M., Forsyth, P.A., Vetzal, K.R., 2003. Numerical convergence properties of option pricing PDEs with uncertain volatility. IMA J. Numer. Anal. 23(2), 241–267.

    Article  MATH  MathSciNet  Google Scholar 

  • Roache, P.J., 1976. Computational Fluid Dynamics. Hermosa, Albuquerque.

    Google Scholar 

  • Sheffield, P.J., Smith, A.P.S., 2002. Hyperbaric Surgery, pp. 63–109. Best Publishing Company.

  • Sherratt, J.A., 1994. Chemotaxis and chemokinesis in eukaryotic cells: the Keller–Segel equations as an approximation to a detailed model. Bull. Math. Biol. 56(1), 129–146.

    MATH  Google Scholar 

  • Siegel, P., Mosè, R., Ackerer, P.H., 1997. Solution of the advection–diffusion equation using a combination of discontinuous and mixed finite volume elements. Int. J. Num. Methods Fluids 24(6), 595–613.

    Article  MATH  Google Scholar 

  • Simpson, M., Landman, K., Clement, T., 2005. Assessment of a non-traditional operator split algorithm for simulation of reactive transport. Math. Comput. Simul. 70(1), 44–60.

    Article  MATH  MathSciNet  Google Scholar 

  • Simpson, M.J., Landman, K.A., Newgreen, D.F., 2006. Chemotactic and diffusive migration on a nonuniformly growing domain: numerical algorithm development and applications. J. Comput. Appl. Math. 192(2), 282–300.

    Article  MATH  MathSciNet  Google Scholar 

  • Skeel, R.D., Berzins, M., 1990. A method for the spatial discretization of parabolic equations in one space variable. SIAM J. Sci. Stat. Comput. 11, 1–32.

    Article  MATH  MathSciNet  Google Scholar 

  • Stokes, C.L., Lauffenburger, D.A., 1991. Analysis of the roles of microvessel endothelial cell random motility and chemotaxis in angiogenesis. J. Theor. Biol. 152(3), 377–403.

    Article  Google Scholar 

  • Stokes, C.L., Rupnick, M.A., Williams, S.K., Lauffenburger, D.A., 1990. Chemotaxis of human microvessel endothelial cells in response to acidic fibroblast growth factor. Lab. Invest. 63(5), 657–668.

    Google Scholar 

  • Stokes, C.L., Lauffenburger, D.A., Williams, S.K., 1991. Migration of individual microvessel endothelial cells: stochastic model and parameter measurement. J. Cell Sci. 99(2), 419–430.

    Google Scholar 

  • Sweby, P., 1984. High resolution schemes using flux limiters for hyperbolic conservation laws. SIAM J. Numer. Anal. 21(5), 995–1011.

    Article  MATH  MathSciNet  Google Scholar 

  • Tandara, A., Mustoe, T., 2004. Oxygen in wound healing—more than a nutrient. World J. Surg. 28, 294–300.

    Article  Google Scholar 

  • Thackham, J., McElwain, D., Long, R., 2008. The use of hyperbaric oxygen therapy to treat chronic wounds: a review. Wound Repair Regen. 16, 321–330.

    Article  Google Scholar 

  • Turner, I.W., 1996. A two-dimensional orthotropic model for simulating wood drying processes. Appl. Math. Model. 20(1), 60–81.

    Article  MATH  Google Scholar 

  • Turner, I.W., Perré, P., 2001. The Use of implicit flux limiting schemes in the simulation of the drying process: a new maximum flow sensor applied to phase mobilities. Appl. Math. Model. 25(6), 513–540.

    Article  MATH  Google Scholar 

  • van Leer, B., 1977. Towards the ultimate conservative difference scheme: IV. A new approach to numerical convection. J. Comput. Phys. 23, 276–299.

    Article  Google Scholar 

  • Zvan, R., Forsyth, P.A., Vetzal, K.R., 2001. A finite volume approach for contingent claims valuation. IMA J. Num. Anal. 21(3), 703–731.

    Article  MATH  MathSciNet  Google Scholar 

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Correspondence to Jennifer A. Thackham.

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Thackham, J.A., Sean McElwain, D.L. & Turner, I.W. Computational Approaches to Solving Equations Arising from Wound Healing. Bull. Math. Biol. 71, 211–246 (2009). https://doi.org/10.1007/s11538-008-9360-z

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