Biomaterials play an essential role in modern medicine replacing and or facilitating normal physiological function. Despite their many advantages they serve as reservoirs for bacterial adhesion and subsequent biofilm infection. These are extremely difficult to treat, displaying resistance to conventional antibiotics up to 1000 times that of planktonic bacteria. In addition, biomaterial associated infections have a significant impact on patient recovery time and healthcare budgets. Researchers are developing biomaterial coatings in order to prevent bacterial adhesion and biofilm development. Taking inspiration from nature, antimicrobial peptides are now coming to the forefront of research and development. Variation of the R group attached to the alpha carbon confers peptides with tailored therapeutic, biodegradable and toxicity profiles. Synthetic peptides may be exploited for a variety of applications including as antimicrobial biomaterials and drug delivery vehicles. Ultrashort peptides (<7 amino acids) are a highly innovative and economical development strategy. These not only possess the tunable properties of longer peptides but they have the ability to self-assemble to hydrogel structures in response to external stimuli including pH, light, temperature and enzymes. Ultrashort self-assembling peptides are considered as novel ’smart’ nanomaterials. This thesis focuses on the development of a library of ultrashort self-assembling peptides prepared following standard Fmoc solid phase synthesis protocols and confirmed using NMR, RP-HPLC and ESI-MS. pH induced assembly resulted in hydrogel formation. Hydrogels were physically characterised using Cryo-SEM, TEM, oscillatory rheology, FTIR, CD and TGA. Antimicrobial activity was determined against a range of Gram-positive and Gram-negative biofilm forming healthcare associated pathogens and in vivo Galleria mellonella infection models. Toxicity profiles were determined via in vitro haemolysis and cell culture assays. The work highlights the promising contribution of ultrashort self-assembling peptides to future biomaterial development.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:709669 |
| Date | January 2016 |
| Creators | McCloskey, Alice Patricia |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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