Multiscale modelling and homogenisation of fibre-reinforced hydrogels for tissue engineering
Tissue engineering aims to grow artificial tissues to replace those in the body that have been damaged through age, trauma or disease. A recent approach to engineer artificial cartilage involves seeding cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres combined with a cast or printed hydrogel, and subjecting the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how the applied load is distributed throughout the construct. To address this, we employ homogenisation theory to derive equations governing the effective macroscale material properties of a periodic, elastic-poroelastic composite. We treat the fibres as a linear elastic material and the hydrogel as a poroelastic material, and exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions) to derive macroscale equations governing the response of the composite to an applied load. This homogenised description reflects the orthotropic nature of the composite. To validate the model, solutions from finite element simulations of the macroscale, homogenised equations are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings and to determine the local mechanical environment experienced by cells embedded within the construct.
Singular perturbation analysis of the steady-state Poisson-Nernst-Planck system: Applications to ion channels
Ion channels are proteins with a narrow hole down their middle that control a wide range of biological function by controlling the flow of spherical ions from one macroscopic region to another. Ion channels do not change their conformation on the biological time scale once they are open, so they can be described by a combination of Poisson and drift-diffusion (Nernst-Planck) equations called PNP in biophysics. We use singular perturbation techniques to analyse the steady-state PNP system for a channel with a general geometry and a piecewise constant permanent charge profile. We construct an outer solution for the case of a constant permanent charge density in three dimensions that is also a valid solution of the one-dimensional system. The asymptotical current-voltage (I-V ) characteristic curve of the device (obtained by the singular perturbation analysis) is shown to be a very good approximation of the numerical I-V curve (obtained by solving the system numerically). The physical constraint of non-negative concentrations implies a unique solution, i.e., for each given applied potential there corresponds a unique electric current (relaxing this constraint yields non-physical multiple solutions for sufficiently large voltages).