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Title: Antibacterial surfaces for medical implant applications
Author: Fleming, George
ISNI:       0000 0004 7964 1977
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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Implantable medical devices are prone to bacterial and biofilm infection, which can lead to serious complications and fatalities in patients. Bacterial resistance to current antibiotics and increasing emergence of healthcare associated infections drives the urgency to develop new antibacterials that do not induce bacterial resistance. In this study the surface chemistry and/or topography of medically relevant polymers, poly(ethylene terephthalate) (PET), silicone elastomer (SE), polystyrene (PS), polycaprolactone (PCL), poly(methyl methacrylate) (PMMA) and polydimethylsiloxane (PDMS) were modified, in an attempt to fabricate synthetic polymers with antibacterial surfaces for use in medical implant applications. Surfaces have been modified chemically to release nitric oxide (NO), a potent antibacterial agent. Physical modifications have led to the fabrication of surfaces with micro- /nanotopographical features that can inhibit bacterial adhesion. In Chapter 4, PET and SE were first aminosilanised to functionalise the surface with amines which facilitate the in situ formation of N-diazeniumdiolates; a class of NO donor that decompose under physiological conditions to release NO. The modified polymers released low levels of NO, which prevented biofilm formation after 24 hrs. In Chapter 5, SE substrates were coated with xerogels. Unlike in Chapter 4, Ndiazeniumdiolates were preformed before incorporation into the xerogel to increase NO storage and release. The N-diazeniumdiolated xerogel coatings released high levels of NO, which resulted in the killing of planktonic (free-moving) bacteria after 1, 4 and 24 hrs. In Chapter 6, PS/PCL, PS/PMMA and PCL/PMMA binary blends were spin coated to form polymer demixed films. By varying the relative concentrations of the polymers in the binary blends, demixed films with island-, ribbon- and pit-like micro- /nanotopographical surface structures were fabricated. When surface structures were smaller than the diameter of the bacterial cell, a reduction in cell adhesion was observed; when the surface structures were comparable in size to the diameter of the bacterial cell no reduction in cell adhesion was observed. In Chapter 7, N-diazeniumdiolate groups were tethered in situ to PDMS replicas with structured microtopographies resulting in novel materials with both distinct surface microfeatures and NO releasing capabilities. Bacterial cell adhesion was reduced on non-releasing structured PDMS compared to non-releasing flat PDMS after 24 hrs, but both surfaces were ineffective in killing bacteria. After 24 hrs, novel dual-action NO-releasing structured PDMS surfaces were both bactericidal and reduced cell adhesion.
Supervisor: D'Sa, Raechelle ; Fothergill, Jo ; Raval, R. ; Hanson, Jenny Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral