Layer-by-layer coatings with multiple antibiofilm functions.

摘要

Bacterial infections of medical devices present a significant societal and scientific challenge as such infections are often resistant to treatment with antibiotics. Medical treatment of these infections is associated with high costs, significant patient discomfort and increased mortality. In this dissertation, we explore several novel ways of constructing highly efficient antibacterial coatings. The approach is based on the layer-by-layer (LbL) technique, which is highly suitable for constructing bioactive functional films due to its applicability to a wide range of synthetic and biological molecules, the use of environmentally friendly aqueous solutions, and the ability to create conformal coatings on substrates of complex shapes.;We describe three novel strategies for building antibiofilm coatings. The first strategy is construction of biocompatible dispersin B-containing LbL coatings that show inhibition of biofilm formation in a poly-N-acetylglucosamine-producing bacterial species, such as Staphylococcus epidermidis, due to degradation of biofilm polysaccharide matrix. The second approach describes designing single-component, weak polyelectrolyte LbL hydrogels for controlled binding and pH-triggered release of antibacterial agents. Since the pH of the surrounding solution decreases during growth of many types of bacteria, such as Staphylococci, we suggest that such coatings present a new type of `smart' coatings with bacteria-triggered release capability. Using ultrathin hydrogels of poly(methacrylic acid), we show that loading and release of several antibacterial agents, such as lysozyme, gentamicin, or a cationic polypeptide, can be controlled by the type of a chemical crosslinker. We contrast the antibacterial activity of different types of LbL hydrogels towards Staphylococcus epidermidis, and discuss results in terms of contact killing and solution-release mechanisms. The third approach combines the two properties, permanent antibiofilm protection and pH-triggered release, within a single coating. This coating comprises a biocompatible clay/polycarboxylic acid LbL assembly, loaded with a widely used antibiotic, gentamicin. We show that there exists a strong and clear relationship between thickness of the LbL films and the extent of inhibition of Staphylococcus aureus growth. These films open new exciting opportunities as highly efficient antibacterial coatings of biomedical and implantable devices.