Development of a nanomedicine in an electrospun patch for wound healing

Abstract

Delays in wound healing are a significant financial burden to the NHS with annual costs estimated to be £3.2 billion. Wound healing is regulated by microRNAs(miRs), which impact multiple aberrant genetic pathways. miR-31 and miR-132 canpromote re-epithelialisation, neoangiogenesis, and anti-inflammatory responses by targeting different molecular pathways. In this thesis, we have encapsulatedmiR-31 and miR-132 into nanoparticles (NP) by electrostatic interaction with RALA, a novel 30-mer amphipathic pH-responsive peptide that is designed to overcome biological barriers. A wound dressing with potential for NP loadingand delivery has been fabricated using electrospinning. Polyvinyl alcohol was chosen as the carrier polymer owing to its ability to be electrospun, sodiumalginate was incorporated for its wound healing ability and ciprofloxacin wasadded as a wide-spectrum antibiotic. The NP cocktail has been proven to efficiently enter cells with no cytotoxicity, to upregulate miR levels, and to increase cell migration. Our NP-loaded electrospun nanofibre technology has demonstrated in vitro antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus, as well as biocompatibility and the promotion of keratinocyte migration in wound scratch assays. Treatment with the loaded nanofibres in a full thickness wound model in C57BL/6N mice resulted in an increase in wound healing rate, as well as a thicker epidermal layer and a heightened blood vessel count.

Thesis embargoed until 31 December 2027

Date of Award	Dec 2022
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	SPaRK
Supervisor	Helen McCarthy (Supervisor) & Nicholas Dunne (Supervisor)