Modelling tissue growth and rearrangements under loading
Lead Research Organisation:
University of Cambridge
Department Name: Engineering
Abstract
Many of the problems that lead to pain and morbidity, and indeed bring patients to the General Practitioner's office, result from changes in soft tissue structure or mechanics. To underpin the physical basis of diseases and develop effective healthcare technologies, one must understand the mechanical properties of soft tissues in their physiological settings.
From an engineering point-of-view, this task is particularly challenging because live tissues are time-evolving materials rarely at rest: they are growing, undergoing rearrangement, and in most cases, do so under various constrains of loads and deformations. Moreover, their behaviour results from phenomena occurring at a wide range of length scales. Yet, existing modelling approaches of tissue growth mainly focus on mechanisms taking place at one particular length scale, hence missing the fundamental interconnections between molecular signals, cellular behaviours and tissue structure.
The objective of the project is to implement a multi-scale model of tissue growth and rearrangement under loading, that integrates extracellular microstructure, cells' individual behaviour and molecular mechanotransduction. The predictions will then be compared with experimental measurements (performed in a parallel project also supported by the EPSRC) and will, in turn, help implement further tissue mechanical assessments.
The research areas involved are biomaterials composite modelling, structural engineering and statistical physics. Theoretical models of scaffold production and degradation (0.7 years), of cell proliferation, motion and forces and of active transport processes (1.5 years) will be build. Computer simulations integrating all the above elements will be simultaneously implemented. Validation and comparison to the experiments will then be covered in the last stage of the PhD (0.8 years).
The expected outcomes notably include a fundamental understanding of the mechanical feedback displayed in inhomogeneous tissue proliferation, which occurs during cancer growth, wound healing or embryonic development. Offering predictions for the optimal mechanical conditioning to engineer compatible tissue implants will also be possible.
This multidisciplinary project in mechanobiology will have impact in biophysics and biomaterials research, which are within the remits of several growing EPSRC's research areas under their core "Healthcare Technologies" theme.
From an engineering point-of-view, this task is particularly challenging because live tissues are time-evolving materials rarely at rest: they are growing, undergoing rearrangement, and in most cases, do so under various constrains of loads and deformations. Moreover, their behaviour results from phenomena occurring at a wide range of length scales. Yet, existing modelling approaches of tissue growth mainly focus on mechanisms taking place at one particular length scale, hence missing the fundamental interconnections between molecular signals, cellular behaviours and tissue structure.
The objective of the project is to implement a multi-scale model of tissue growth and rearrangement under loading, that integrates extracellular microstructure, cells' individual behaviour and molecular mechanotransduction. The predictions will then be compared with experimental measurements (performed in a parallel project also supported by the EPSRC) and will, in turn, help implement further tissue mechanical assessments.
The research areas involved are biomaterials composite modelling, structural engineering and statistical physics. Theoretical models of scaffold production and degradation (0.7 years), of cell proliferation, motion and forces and of active transport processes (1.5 years) will be build. Computer simulations integrating all the above elements will be simultaneously implemented. Validation and comparison to the experiments will then be covered in the last stage of the PhD (0.8 years).
The expected outcomes notably include a fundamental understanding of the mechanical feedback displayed in inhomogeneous tissue proliferation, which occurs during cancer growth, wound healing or embryonic development. Offering predictions for the optimal mechanical conditioning to engineer compatible tissue implants will also be possible.
This multidisciplinary project in mechanobiology will have impact in biophysics and biomaterials research, which are within the remits of several growing EPSRC's research areas under their core "Healthcare Technologies" theme.