Mathematical modelling of the growth of soft biological tissues
Mathematical modelling of the growth of soft biological tissues
The work presented in this thesis is concerned with mathematically modelling the growth and development of soft biological tissues. This work embodies a collection of three investigations that use mathematical techniques to examine the roles of possible mechanisms within two established experimental models, the multicellular tumour spheroid and tissue-engineered articular cartilage.
The thesis begins by addressing the phenomenon of tumour regrowth, observed both clinically and experimentally in chemotherapeutic research. The direction we take in this investigation deviates from the usual explanation put forward, namely, that of chemoresistance, to consider a newly proposed theory. A model is developed, based on the hypothesis that drug-induced cell death in the peripheral layer of the spheroid produces a weakening in the spheroid surface tension, allowing large amounts of extracellular space to develop within treated spheroids, which causes them to overtake in size the non-treated controls. A comparison between model predictions and experimental evidence supports the proposed hypothesis, but suggests that further mechanisms must be considered in order to quantitatively match the extent of regrowth reported experimentally.
Theoretical methods, similar to those used in the work described above, are also employed to study the problem of heterogeneous proliferation within cell-polymer constructs, frequently reported in the field of tissue engineering of articular cartilage.
Finally, we address the need for a better understanding of the physical processes involved in the production and deposition of extracellular matrix in engineered cartilaginous pellets. A theoretical investigation is carried out alongside experimental work using ATDC5 cell pellets.
University of Southampton
2007
Lewis, Miranda Claire
(2007)
Mathematical modelling of the growth of soft biological tissues.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The work presented in this thesis is concerned with mathematically modelling the growth and development of soft biological tissues. This work embodies a collection of three investigations that use mathematical techniques to examine the roles of possible mechanisms within two established experimental models, the multicellular tumour spheroid and tissue-engineered articular cartilage.
The thesis begins by addressing the phenomenon of tumour regrowth, observed both clinically and experimentally in chemotherapeutic research. The direction we take in this investigation deviates from the usual explanation put forward, namely, that of chemoresistance, to consider a newly proposed theory. A model is developed, based on the hypothesis that drug-induced cell death in the peripheral layer of the spheroid produces a weakening in the spheroid surface tension, allowing large amounts of extracellular space to develop within treated spheroids, which causes them to overtake in size the non-treated controls. A comparison between model predictions and experimental evidence supports the proposed hypothesis, but suggests that further mechanisms must be considered in order to quantitatively match the extent of regrowth reported experimentally.
Theoretical methods, similar to those used in the work described above, are also employed to study the problem of heterogeneous proliferation within cell-polymer constructs, frequently reported in the field of tissue engineering of articular cartilage.
Finally, we address the need for a better understanding of the physical processes involved in the production and deposition of extracellular matrix in engineered cartilaginous pellets. A theoretical investigation is carried out alongside experimental work using ATDC5 cell pellets.
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Published date: 2007
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Local EPrints ID: 466058
URI: http://eprints.soton.ac.uk/id/eprint/466058
PURE UUID: 172a5714-aea3-4264-bbce-d8828dd5a3f0
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Date deposited: 05 Jul 2022 04:11
Last modified: 05 Jul 2022 04:11
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Author:
Miranda Claire Lewis
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