New mathematical models for perfusion bioreactors in tissue engineering
Lead Research Organisation:
University of Oxford
Department Name: Mathematical Institute
Abstract
The goal of tissue engineers is to grow functional tissues and organs in the laboratory to replace those which have become defective through age, trauma, and disease, and which can be used in drug screening applications. To achieve this goal, tissue engineers aim to control accurately the biomechanical and biochemical environment of the growing tissue construct, in order to engineer tissues with the desired properties. A common approach is to place a porous biomaterial scaffold, seeded with cells, in a flow perfusion bioreactor. Perfusion bioreactors offer the potential for enhanced mass transfer to the construct (overcoming diffusion limitations encountered in static culture environments). Furthermore, such bioreactors are increasingly being used to provide mechanical loads to mechanosensitive tissues which accelerates tissue formation in vitro, thus minimising production time. When determining the optimum stimulatory environment required to generate in vitro a tissue construct that remains functional for significant periods of time, tissue engineers typically adopt a reductionist experimental approach in which attention is focused on a component part of the system. However, the system is more than the sum of its parts, and the challenge lies in determining how all the components interact. Mathematical modelling has a central role to play in elucidating the mechanisms underlying the complex fluid-tissue interactions in such perfusion systems.The proposed research will formulate and solve novel mathematical models to provide fundamental insights into the role of the fluid flow in ensuring adequate substrate delivery to the biologically active porous medium, and optimising the stress field felt by the mechanosensitive tissue. This is a challenging mathematical problem as the biological system is highly complex involving numerous mechanical and chemical interactions between mixed cell populations in spatially and temporally evolving domains. A feature of the research will be continual dialogue with internationally-leading experimental researchers; this will facilitate the calibration, verification and refinement of the theoretical models, and enable theoretical predictions to be experimentally tested.
Organisations
People |
ORCID iD |
Sarah Waters (Principal Investigator) |
Publications
Waters SL
(2011)
Theoretical models for coronary vascular biomechanics: progress & challenges.
in Progress in biophysics and molecular biology
O'Dea RD
(2013)
The interplay between tissue growth and scaffold degradation in engineered tissue constructs.
in Journal of mathematical biology
Neßler KHL
(2016)
The influence of hydrostatic pressure on tissue engineered bone development.
in Journal of theoretical biology
Osborne JM
(2010)
The influence of bioreactor geometry and the mechanical environment on engineered tissues.
in Journal of biomechanical engineering
Chapman LA
(2014)
Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
in PloS one
Green JE
(2010)
Non-local models for the formation of hepatocyte-stellate cell aggregates.
in Journal of theoretical biology
Pearson NC
(2014)
Multiphase modelling of the influence of fluid flow and chemical concentration on tissue growth in a hollow fibre membrane bioreactor.
in Mathematical medicine and biology : a journal of the IMA
Pearson N
(2014)
Multiphase modelling of the effect of fluid shear stress on cell yield and distribution in a hollow fibre membrane bioreactor
in Biomechanics and Modeling in Mechanobiology
Whittaker RJ
(2009)
Mathematical modelling of fibre-enhanced perfusion inside a tissue-engineering bioreactor.
in Journal of theoretical biology
Pohlmeyer JV
(2013)
Mathematical model of growth factor driven haptotaxis and proliferation in a tissue engineering scaffold.
in Bulletin of mathematical biology
Lemon G
(2011)
Growth of the chorioallantoic membrane into a rapid-prototyped model pore system: experiments and mathematical model.
in Biomechanics and modeling in mechanobiology
Shipley R
(2011)
Fluid and mass transport modelling to drive the design of cell-packed hollow fibre bioreactors for tissue engineering applications
in Mathematical Medicine and Biology
Shipley R
(2011)
Fluid and mass transport modelling to drive the design of cell-packed hollow fibre bioreactors
in European Cells and Materials
Reinwald Y
(2015)
Evaluation of the growth environment of a hydrostatic force bioreactor for preconditioning of tissue-engineered constructs.
in Tissue engineering. Part C, Methods
Pearson N
(2015)
Dispersion-enhanced solute transport in a cell-seeded hollow fibre membrane bioreactor
in Journal of Engineering Mathematics
Shipley RJ
(2010)
Definition and validation of operating equations for poly(vinyl alcohol)-poly(lactide-co-glycolide) microfiltration membrane-scaffold bioreactors.
in Biotechnology and bioengineering
O'DEA R
(2008)
A two-fluid model for tissue growth within a dynamic flow environment
in European Journal of Applied Mathematics
Shipley RJ
(2011)
A strategy to determine operating parameters in tissue engineering hollow fiber bioreactors.
in Biotechnology and bioengineering
O'Dea RD
(2015)
A multiscale analysis of nutrient transport and biological tissue growth in vitro.
in Mathematical medicine and biology : a journal of the IMA
O'Dea RD
(2010)
A multiphase model for tissue construct growth in a perfusion bioreactor.
in Mathematical medicine and biology : a journal of the IMA
Pearson NC
(2016)
A multiphase model for chemically- and mechanically- induced cell differentiation in a hollow fibre membrane bioreactor: minimising growth factor consumption.
in Biomechanics and modeling in mechanobiology
Green JE
(2009)
A mathematical model of liver cell aggregation in vitro.
in Bulletin of mathematical biology
Shakeel M
(2013)
A continuum model of cell proliferation and nutrient transport in a perfusion bioreactor.
in Mathematical medicine and biology : a journal of the IMA