Development of stimuli-responsive hydrogels to combat infection of biomaterials

• Main Author: Trotter, Johann Louise
• Published: Queen's University Belfast 2017
• Subjects: 615
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.728682

The development of medical device-associated infections is an increasing burden on modern healthcare. Currently there are no methods fully effective at preventing or eradicating these infections. The aim of this thesis was to develop stimuli-responsive hydrogels as new alternative methods to try and combat such infections, with particular focus placed on catheter-associated urinary tract infections (CAUTIs). Urease-producing bacteria, such as Proteus mirabilis, are prevalent organisms in CAUTIs and cause an increase in pH at the catheter surface. This change in pH was exploited in this thesis wherein a pH- triggered system has been developed and characterised, comprised of a surfactant tethered to a polymeric backbone. An increase in pH was shown to cleave these bonds and accelerate the release of surfactant with 5 times more surfactant released at pH 10 than pH 7 after 28 days. Materials were also shown to demonstrate significant reductions in antimicrobial adherence when challenged with Proteus mirabilis and Staphylococcus aureus. A low-friction coating with an improved dry-out time for intermittent catheters has also been characterised and the effect of retraction speed during the dip coating process on a number of different parameters has been assessed. The highly effective chlorhexidine diacetate has also been incorporated into the coating as a means of enhancing antimicrobial efficacy with up to 5 log reductions in bacterial adherence observed. Lastly, a photolabile crosslinker was developed and incorporated into hydrogels to produce a photoresponsive material. Irradiation of the materials was shown to cleave the crosslinker, increasing porosity and subsequently swelling and drug release. This thesis therefore provides a range of novel materials that have been shown to display antimicrobial or anti-adherent properties and therefore have demonstrated a potential applicability to prevent medical device infections.