Abstract
We consider a continuum mathematical model of biological tissue formation inspired by recent experiments describing thin tissue growth in 3D-printed bioscaffolds. The continuum model, which we call the substrate model, involves a partial differential equation describing the density of tissue, {hat{u}}(hat{{mathbf {x}}},{hat{t}}) that is coupled to the concentration of an immobile extracellular substrate, {hat{s}}(hat{{mathbf {x}}},{hat{t}}). Cell migration is modelled with a nonlinear diffusion term, where the diffusive flux is proportional to {hat{s}}, while a logistic growth term models cell proliferation. The extracellular substrate {hat{s}} is produced by cells and undergoes linear decay. Preliminary numerical simulations show that this mathematical model is able to recapitulate key features of recent tissue growth experiments, including the formation of sharp fronts. To provide a deeper understanding of the model we analyse travelling wave solutions of the substrate model, showing that the model supports both sharp-fronted travelling wave solutions that move with a minimum wave speed, c = c_{mathrm{min}}, as well as smooth-fronted travelling wave solutions that move with a faster travelling wave speed, c > c_{mathrm{min}}. We provide a geometric interpretation that explains the difference between smooth and sharp-fronted travelling wave solutions that is based on a slow manifold reduction of the desingularised three-dimensional phase space. In addition, we also develop and test a series of useful approximations that describe the shape of the travelling wave solutions in various limits. These approximations apply to both the sharp-fronted and smooth-fronted travelling wave solutions. Software to implement all calculations is available at GitHub.
Highlights
Over the last decade, tissue engineering has been revolutionised through the use of 3D printing technologies that produce 3D bioscaffolds upon which in vitro tissues can be grown in biologically realistic geometries (Ambrosi et al 2019; Dzobo et al 2018)
In this study we investigated a minimal model of cell invasion that couples cell migration, cell proliferation and cell substrate production and decay
This feature leads to predictions of tissue formation involving the propagation of well-defined sharp fronts, and two-dimensional numerical simulations of the mathematical model recapitulate key features of recent experiments that involved the formation of thin tissues grown on
Summary
Tissue engineering has been revolutionised through the use of 3D printing technologies that produce 3D bioscaffolds upon which in vitro tissues can be grown in biologically realistic geometries (Ambrosi et al 2019; Dzobo et al 2018). While these studies show that simple mathematical models based on the Fisher-KPP framework successfully capture certain features of tissue formation, there are several well-known limitations that can be addressed by considering extensions of that model (Murray 2002) Within this modelling framework, it is natural for us to ask how the duration of time required for the pore to close is affected by the dynamics of substrate deposi-
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