Gonzalez-Molina, Jordi;
(2018)
Cell-biomaterial mechanical interactions: from cancer mechanobiology to cell therapies.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Cell-biomaterial mechanical interactions: from cancer mechanobiology to cell therapies |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Keywords: | Biomaterials, Mechanobiology, Cancer, Bioartificial liver, Viscosity. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10052561 |
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