Ahmed, Jubair; (2022) The Tailored Production of Small Diameter Fibres and Their Applications in Wound Healing. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Thinner fibres benefit from a high surface area to volume ratio which is valuable in many biomedical applications ranging from tissue engineering to drug delivery and wound healing. Fibre forming technologies such as electrospinning and pressurised gyration rely on the careful manipulation of solution properties as well as working parameters to obtain the most optimal fibre morphology for their intended applications. In deeply understanding how these fibre manufacturing technologies work, there can be highly optimised and tailored production of polymeric biomaterials. Natural substances represent a class of materials that fail to be forgotten for use in health-related applications. Honey and cinnamon have gained significant interest not only for their physical and chemical properties but also for their antibacterial activity. Manuka Honey UMF 20+ was examined for its antibacterial properties against Escherichia coli and Staphylococcus epidermidis using flow cytometry where the active agent is thought to be the high methylglyoxal content. The inhibitory effect of manuka honey on bacterial growth was evident at concentrations ranging from 10 to 30 v/v%, where higher concentrations benefited from additional honey loading. The incorporation of Manuka honey as an antibacterial agent was explored as a potential route for manufacturing wound dressing components. Using pressurised gyration, scaffolds of sub-micrometre fibres were formed from 10, 20 and 30 v/v% Manuka honey which were incorporated into the polycaprolactone polymer solutions. The composite fibres were analysed for their morphology and topography using scanning electron microscopy. The average fibre diameter of the Manuka honey-polycaprolactone scaffolds was found to be in the range of 437 to 815 nm. The antibacterial activity of the most potent 30 v/v% scaffolds was studied against S. epidermidis. The scaffolds showed strong antibacterial activity with a bacterial reduction rate of over 90%. The results here show that honey composite fibres can be considered a natural therapeutic agent for wound healing applications. Fibrous bandage-like constructs made with incorporated cinnamon extract have been previously shown to have potent antifungal abilities which surpass even the raw material itself. The question remains as to whether these constructs are useful in the prevention of bacterial infections and what the antimicrobial effect means in terms of toxicity to native physiological cells. In this work cinnamon-extracted fibres are tested against Staphylococcus epidermidis to assess their antibacterial capacity; it was found that the fibres were able to successfully kill the bacteria. The constructs were also tested under indirect MTT cytotoxicity tests involving the L929 mouse fibroblast cell line, where they showed no variation from the control groups in terms of toxicity. Additionally, cell viability imaging showed no significant toxicity issues with the fibres, even at their tested highest concentration. Here I present a viable method to produce wound healing products made from non-toxic and abundant naturally occurring materials such as cinnamon. Two fibre forming techniques, pressurised gyration and electrospinning have been combined to create a manufacturing process where advanced wound healing bandages can be created. This new hybrid process leverages the rapid production rate of pressurised gyration to create the bulk portion of the bandages and exploits the precise nature of electrospinning to directly print a bioactive fibrous patch onto the active site of the bandages. Polycaprolactone bandages have thus been created which have a bioactive patch consisting of collagen and chitosan with a poly(ethylene oxide) support. The patches have an average fibre diameter of 173 ± 27 nm and closely resemble the extracellular matrix in its structure, together with the active collagen and chitosan, this will be crucial in their ability to facilitate advanced wound healing. Additionally, synthetic materials such as antimicrobial nanoparticles can be added to the patches which demonstrate that the manufacturing technique is not limited to only using natural materials. Patches with these nanoparticles had an average fibre diameter of 142 ± 31 nm and demonstrated that very uniform and thin fibres could be created with these materials. The process has a great degree of automation and has potential for industrial scalability. The advancement of manufacturing processes needs to be supported by the discovery of novel materials and novel combinations of existing materials. Graphene possesses many properties that have predominately been investigated for commercial applications. For the first time, porous graphene (PG) has been incorporated into polymer matrices produced by a high-output manufacturing process. Graphene and its other derivates such as graphene oxide have been shown to provide an antibacterial surface that can mechanically kill pathogens that encounter it. For this reason, graphene nanopores presents itself as a viable additive for wound healing materials. This overarching work focuses on the production of small diameter fibres via multiple techniques to achieve the most control over the final fibre morphology for uses in advanced wound healing materials.

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