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Register a new userA simplified multiphase multiscale model for tissue growth
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In this paper, we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. As in our recent work (Holden textit{et al.} A multiphase multiscale model for nutrient limited tissue growth, The ANZIAM Journal, 2018, doi:10.1017/S1446181118000044) the underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearisation of the underlying multiphase model (whose nonlinearity poses significant challenge for such analyses), we obtain, by means of multiple-scales homogenisation, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics. The model we obtain comprises Darcy flow, and differential equations for the volume fraction of cells within the scaffold and the concentration of nutrient, required for growth. These are coupled to underlying Stokes-type cell problems that provide permeability tensors to parameterise the macroscale description. In Holden textit{et al.}, the cell problems retain macroscale dependence, posing significant computational challenges; here, we obtain a decoupled system whereby the quasi-steady cell-problems may be solved separately from the macroscale description, thereby greatly reducing the complexity associated with fully-coupled multiscale descriptions. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.S
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Identifying the mechanism of intercellular feedback regulation is critical for the basic understanding of tissue growth control in organisms. In this paper, we analyze a tissue growth model consisting of a single lineage of two cell types regulated by negative feedback signalling molecules that undergo spatial diffusion. By deriving the fixed points for the uniform steady states and carrying out linear stability analysis, phase diagrams are obtained analytically for arbitrary parameters of the model. Two different generic growth modes are found: blow-up growth and final-state controlled growth which are governed by the non-trivial fixed point and the trivial fixed point respectively, and can be sensitively switched by varying the negative feedback regulation on the proliferation of the stem cells. Analytic expressions for the characteristic time scales for these two growth modes are also derived. Remarkably, the trivial and non-trivial uniform steady states can coexist and a sharp transition occurs in the bistable regime as the relevant parameters are varied. Furthermore, the bi-stable growth properties allows for the external control to switch between these two growth modes. In addition, the condition for an early accelerated growth followed by a retarded growth can be derived. These analytical results are further verified by numerical simulations and provide insights on the growth behavior of the tissue. Our results are also discussed in the light of possible realistic biological experiments and tissue growth control strategy. Furthermore, by external feedback control of the concentration of regulatory molecules, it is possible to achieve a desired growth mode, as demonstrated with an analysis of boosted growth, catch-up growth and the design for the target of a linear growth dynamic.
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The electrical coupling between myocytes and fibroblasts and the spacial distribution of fibroblasts within myocardial tissues are significant factors in triggering and sustaining cardiac arrhythmias but their roles are poorly understood. This article describes both direct numerical simulations and an asymptotic theory of propagation and block of electrical excitation in a model of atrial tissue with myocyte-fibroblast coupling. In particular, three idealised fibroblast distributions are introduced: uniform distribution, fibroblast barrier and myocyte strait, all believed to be constituent blocks of realistic fibroblast distributions. Primary action potential biomarkers including conduction velocity, peak potential and triangulation index are estimated from direct simulations in all cases. Propagation block is found to occur at certain critical values of the parameters defining each idealised fibroblast distribution and these critical values are accurately determined. An asymptotic theory proposed earlier is extended and applied to the case of a uniform fibroblast distribution. Biomarker values are obtained from hybrid analytical-numerical solutions of coupled fast-time and slow-time periodic boundary value problems and compare well to direct numerical simulations. The boundary of absolute refractoriness is determined solely by the fast-time problem and is found to depend on the values of the myocyte potential and on the slow inactivation variable of the sodium current ahead of the propagating pulse. In turn, these quantities are estimated from the slow-time problem using a regular perturbation expansion to find the steady state of the coupled myocyte-fibroblast kinetics. The asymptotic theory gives a simple analytical expression that captures with remarkable accuracy the block of propagation in the presence of fibroblasts.
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