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Predicting the mechanical cues experienced by hydrogel-coated stem cells in transit to the liver

ORAL

Abstract

Liver diseases are the fastest-growing major cause of death in the UK, with a 400%

increase since 1970. Stem cell therapies are a promising alternative to unsustainable

liver transplants. However, stem cells do not always engraft onto damaged liver tissue,

reducing the efficacy of these treatments. Encapsulating the cells can increase the

probability of engraftment at the site of damage. The coating protects the cell from an

immune response and modulates the mechanical cues (shear, deformation) inflicted

on the cell. Cells respond to mechanical cues by expressing cell-surface proteins. We

aim to predict and control these mechanical cues by tuning the coating properties to

promote specific protein expression, consequently increasing adhesion and improv-

ing the probability of engraftment. We model an individual, hydrogel-coated stem cell

moving along a fluid-filled channel due to a Stokes flow. The stem cell is treated as

a Newtonian fluid and the coating is treated as a poroelastic material with finite thick-

ness. In the limit of a stiff coating, a semi-analytical approach is developed which

exploits a decoupling of the fluids and solid problems. This enables the tractions

and pore pressures within the coating to be obtained, which then feed directly into a

purely solid mechanics problem for the coating deformation. We conduct a parametric

study to elucidate how the properties of the coating can be tuned to alter the defor-

mation and stress experienced by the cell. We validate the semi-analytical framework

by numerically solving the fluid structure interaction problem, demonstrating suitable

agreement between the results.

Presenters

  • Simon Finney

    University of Oxford

Authors

  • Simon Finney

    University of Oxford

  • Sarah L Waters

    University of Oxford, Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, University of Oxford

  • Matthew Hennessy

    University of Bristol

  • Andreas Muench

    University of Oxford