Catalyst Reincarnation: Post-Polymerisation Functionality of Ring-Opening Polymerisation Catalysts as Bioactive Additives in Biomedical Devices

Abstract

This research aims to form a series of biopolymers (Poly-lactide, PLA) for the use as medical devices, specifically for the use as antimicrobial thin film coatings to combat postoperative infection. If an infection occurs patient health is at risk, particularly with surgeries such as joint-replacements where metal implants are already a strain on the body.

The use of bismuth complexes as antimicrobial catalysts for the ring-opening polymerisation (ROP) of lactide is intended to reduce environmental damage through repurposing the metal catalyst, removing the need for further antimicrobial additives and
reducing the need to remove previously used toxic catalysts. This will result in a reduceduse of resources and time resulting in a more sustainable and useful polymer product.

Chapter 1 details the relevant literature background: the synthesis of PLA including reaction mechanisms and typical catalyst systems; applications of bismuth as an antimicrobial agent and methods of forming functionalised polymers.

Chapter 2 addresses the clinical problem of post-operative infection, the suggested method to combat this and the aims of this thesis.

Chapter 3 describes the use of commercially available bismuth compounds; triphenyl bismuth, bismuth subsalicylate and bismuth acetate, to form PLA via ROP methods; the characterisation of the resultant polymers were completed.

Chapter 4 sees the formation of homoleptic bismuth(III) complexes using a series of α-hydroxy ketones as ligands in the system. The formation, characterisation and biological activity towards Gram-positive and -negative bacteria and mammalian cells is investigated
and discussed for these compounds. The antimicrobial efficacy of the alpha-hydroxy ketones improved upon coordination to the bismuth centre and show favourable selectivity profiles.


Chapter 5 investigates the use of these bismuth tris-α-hydroxyketones as novel ROP catalysts forming PLA through the homopolymerisation of lactide to form a linear or telechelic polymer chain. The polymers formed were investigated for their typical polymer properties: mechanical, thermal and the bismuth content. Promising results are seen for the activity of the bismuth tris-alpha hydroxy ketones towards ROP with retention of bismuth within the polymer observed.

Chapter 6 investigates the application of the polymers formed in chapter 5 through study of the bismuth leaching rates and bacterial growth inhibition. Factors effecting the leaching rate are considered and discussed such as: polymer molecular weight, bismuth
compound solubility and polymer crystallinity. Polymers catalysed from Bi(Trop)3 showed promising activity with antimicrobial efficacy towards multiple strains of bacteria including some of those which are clinically important.

Date of Award	26 Jun 2024
Original language	English
Awarding Institution	University of Bath
Supervisor	Matthew Davidson (Supervisor), Philip Andrews (Supervisor), Laurence Meagher (Supervisor) & Antoine Buchard (Supervisor)