Biocompatible polymer microarrays for cellular high-content screening
The global aim of this thesis was to study the use of microarray technology for the screening and identification of biocompatible polymers, to understand physiological phenomena, and the design of biomaterials, implant surfaces and tissue-engineering scaffolds. This work was based upon the polymer microarray platform developed by the Bradley group. Polymer microarrays were successfully applied to find the best polymer supports for: (i) mouse fibroblast cells and used to evaluate cell biocompatibility and cell morphology. Fourteen polyurethanes demonstrated significant cellular adhesion. (ii) Analysis of the adhesion of human erythroleukaemic K562 suspension cells onto biomaterials with particular families of polyurethanes and polyacrylates identified. A DNA microarray study (to access the global gene expression profiles upon cellular binding) demonstrated that interactions between cells and some polyacrylates induced a number of transcriptomic changes. These results suggested that, during these interactions, a chain of cellular changes is triggered, most notably resulting in the downregulation of membrane receptors and ligands. (iii) Identification of polymers with potential applications in the field of stem cell biology. Polymers were identified that showed attachment, promotion and stabilisation of hepatocyte-like cells. A polyurethane support (PU-134) was pinpointed, which significantly improved both hepatocyte-like cell function and “lifespan”. A second project investigated biomaterials that promoted adhesion, growth and function of endothelial progenitor cells. A new polymer matrix was identified which contained the necessary signals to promote endothelial phenotype and function. This has potential application in the creation of blood vessels and the endothelialisation of artificial vessel prostheses and stent coatings for improving angioplasty therapy. (iv) The study of bacterial adhesion, focusing on the adhesion of food-borne pathogenic bacterium Salmonella enterica serovar typhimurium, strain SL1344, and the commensal bacterium Escherichia coli, strain W3110. Several polymers were found to support selective bacterial enrichment, as well as others that minimised bacterial adhesion.