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Title: Cell-biomaterial mechanical interactions : from cancer mechanobiology to cell therapies
Author: Gonzalez-Molina, Jordi
ISNI:       0000 0004 7429 1023
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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The physical characteristics of the cell microenvironment greatly affect cellular processes such as survival, proliferation, migration, and differentiation. Biomaterials with well-defined physical and chemical properties have been used to better understand the cell microenvironment. Furthermore, the physicochemical properties of biomaterials can be modulated to induce host body responses and therapeutic cell behaviour. Based on these premises, the work presented in this thesis investigated the effect of soluble polymers commonly used in cell therapies on the physical properties of the extracellular microenvironment. It was found, that viscosity-enhancing polymers induce mesenchymal migration in liver cancer cells, an effect derived from changes in integrin-dependent cell – substrate adhesion dynamics and mechanosensing. Also, the role of extracellular polymers on endothelial-derived cell alignment was explored indicating that molecular soluble polymers enhance cell elongation and alignment in a molecular weight-dependent manner. In addition, the effect of hydrogel density and crosslinking causing mechanical confinement was found to affect cancer cell growth and cell cycle progression, leading to an enhanced content in polyploid cells. Finally, the effect of mechanical confinement on liver cancer cells was taken advantage of to improve the production of biomass for a bioartificial liver device by modulating the degree of crosslinking of alginate hydrogel. In conclusion, the work presented here indicates that physical properties of both the extracellular fluid and matrix greatly affect cell behaviour and can be exploited to improve biomaterial design for in vitro testing and clinical applications.
Supervisor: Selden, C. ; Fuller, B. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available