Walsh, CL;
(2017)
Validation and development of extravascular bubble models for decompression sickness using collagen hydrogel.
Doctoral thesis , UCL (University College London).
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Abstract
For over 200 years, the formation of bubbles in the body as a result of ambient pres- sure changes has been linked to decompression sickness (DCS). The mechanisms by which bubbles may lead to DCS are poorly understood, despite this long history of re- search. Mathematical modelling has played a key role in DCS prevention through the development of dive computer algorithms. Algorithms which incorporate mechanistic bubble models must make assumptions about a selected bubble property being statisti- cally related to the incidence of DCS. This poses a problem for the validation of such algorithms. Given the uncertain relationship between the mechanistic model output and the symptoms of DCS, direct bubble observation is required to validate the mechanistic portion of the model; such measurements, however, are not currently possible in vivo. The use of biomimetic in vitro models provides a new research avenue to investigate the causal mechanism as well address the validation problem currently faced. In the work described in this thesis an in vitro matrix model (collagen type I gel) was used to validate and further develop a 3D computational model of extravascular bubble dynamics. The collagen gels together with a microscope compatible pressure chamber provided the means to directly measure bubble formation and dynamics within the gels during decompression profiles. The effect of material and dive parameter vari- ations on bubble growth was first investigated and validated. Bubble-bubble interaction and coalescence were then analysed. Both the computational and experimental results of these analyses indicated that a model of bubble nucleation would be essential to model bubble dynamics accurately. The possible nature and distribution of nucleation sites was investigated. Options for incorporation of the nucleation findings are anal- ysed. Finally the influence of live cells bubble dynamics through oxygen consumption and the effect bubble proximity has on cell viability were investigated.
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