DEVELOPING SOFT HIERARCHICALLY-STRUCTURED BIOMATERIALS USING PROTEINS AND BACTERIOPHAGES

Abstract

Bio-interface topography strongly affects the nature and efficiency of interactions with living cells and biological molecules, making hydrogels decorated with micro and nanostructures an attractive choice for a wide range of biomedical applications. Despite the distinct advantages of protein hydrogels, literature in the field has disproportionately focused on synthetic polymers to the point that most methods are inherently incompatible with proteins and heat-sensitive molecules. We report the development of multiple biomolecule-friendly technologies to construct microstructured protein and bacteriophage (bacterial virus) hydrogels. Firstly, ordered and sphericity-controllable microbumps were obtained on the surface of protein hydrogels using polystyrene microporous templates. Addition of protein nanogels resulted in the hierarchical nano-on-micro morphology on the microbumps, exhibiting bacterial repellency 100 times stronger than a flat hydrogel surface. The developed microstructures are therefore especially suitable for antifouling applications. The microstructures created on protein hydrogels paved the way for applying honeycomb template on proteinous bacterial viruses. We developed a high-throughput method to manufacture isolated, homogenous, pure and hybrid phage microgels. The crosslinked phages in each phage-exclusive microgel self-organized and exhibited a highly-aligned nanofibrous texture. Sprays of hybrid microgels loaded with potent virulent phage effectively reduced heavy loads of multidrug resistant Escherichia coli O157:H7 on food products by 6 logs.