Oxygen-generating biomaterials for use in wound dressing strategies

Abstract

The aim of the work undertaken in this thesis was to investigate the application of biodegradable, oxygen generating matrices for potential use in treating chronic wounds. Chapter 1 introduces factors contributing to delayed wound healing, existing state of the art treatments, their limitations and the potential use of oxygen generating materials in treating chronic wounds. Chapter 2 provides the experimental methodologies used across Chapters 3-5. Chapter 3 describes the production and characterisation of CaO2 NPs that are then incorporated into the biodegradable polymers PLGA, PCL and PLA to produce oxygen generating matrices. Oxygen generation was assessed by measuring the production of dissolved oxygen. Chapter 4 explores the antibacterial activity of the oxygen generating matrices and their potential to address wound infections. Results demonstrated that of the three polymers, PLGA matrices containing CaO2 NPs had a significant antibacterial effect against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. PLGA matrices were subsequently tested against P. aeruginosa biofilm models and a significant decrease in bacterial CFUs was observed after 8 h. The addition of US enhanced this antibacterial effect further, suggesting that this approach could provide a novel, stimulus response wound management material, capable of delivering an antibacterial effect on demand. Chapter 5 investigates the ability of oxygen generating materials to overcome a hypoxic environment and consequentially enhance wound healing. Initially, this involved examining the cytotoxicity of both freeCaO2 NPs and oxygen generating matrices, to identify optimal treatment concentrations. An in vitro scratch assay was developed as a wound healing model, demonstrating a hypoxia-induced delay in scratch closure when compared to normoxic conditions. Using this model, both PLGA and PLA matrices could generate sufficient oxygen to overcome the hypoxic-induced delay in wound closure. Furthermore, RT-qPCR analysis using PLGA matrices confirmed this with decreased expression of HIF-1α and VEGF-A genes. The final chapter provides overall conclusions arrived at from the data and suggests future direction to develop the full potential of the approach. Overall, the findings indicate that these novel oxygen generating matrices offer significant potential in overcoming the major barriers of hypoxia and infection to effective chronic wound healing.

Date of Award	Jun 2025
Original language	English
Supervisor	Anthony McHale (Supervisor) & John Callan (Supervisor)