Thesis Format
Integrated Article
Degree
Doctor of Philosophy
Program
Biomedical Engineering
Supervisor
Gillies, Elizabeth R.
2nd Supervisor
Ragogna, Paul J.
Co-Supervisor
Abstract
The goal of this thesis is to develop potential solutions to prevent bacterial growth on surfaces, using stimuli-sensitive antibacterial coatings. First, pH-sensitive coatings were synthesized using phosphonium monomers with different substituents, along with two different types of crosslinkers: one ketal-based and the other acetal-based. These components were combined and subjected to UV curing. Analysis of coating properties revealed a mild hydrophilic character, along with high charge density and gel content. Degradation studies of these coatings, employing ketal or acetal-based crosslinkers, demonstrated that ketal-based coatings underwent faster degradation at pH 5.0 compared to acetal-based coatings, resulting in the release of more phosphonium species at pH 5.0. Furthermore, antibacterial studies showcased the bactericidal efficacy of these pH-sensitive phosphonium coatings. At pH 5.0, ketal-based coatings exhibited superior performance, leading to complete eradication of Staphylococcus aureus and Escherichia coli, as confirmed by the counting of colony forming units and fluorescence microscopy analysis using green fluorescence protein-expressing bacteria. Further enhancements to these pH-sensitive phosphonium coatings were made by incorporating the antibiotic gentamicin. A gentamicin monomer with the drug conjugated to a polymerizable styrenic group through a pH-sensitive imine linkage was incorporated into the coating formulation. Analysis of coating properties revealed a higher hydrophilic feature and a slight enhancement in gel content compared to the non-gentamicin coatings. Drug release studies demonstrated that gentamicin was released more rapidly when utilizing ketal-based coatings compared to acetal-based coatings. Bacterial studies indicated complete eradication of bacteria irrespective of the coating composition. Additionally, thermo-sensitive coatings were explored in combination with inductive heating. Combinations of different antibiotics and poly(ester amide) were utilized, and the final coatings were obtained through drop casting. Upon reaching a temperature above the glass transition temperature of the poly(ester amide), antibiotics were released at an accelerated rate. Various temperature conditions were explored to assess the thermo-responsive behavior of the poly(ester amide), including the application of inductive heating. Higher temperatures led to more rapid release of the drug. Bacterial studies revealed that these coatings, when subjected to inductive heating combined with antibiotic release, exhibited an enhanced bactericidal effect confirmed by crystal violet and fluorescence microscopy.
Summary for Lay Audience
Joint replacement surgery offers significant benefits by relieving pain and restoring joint function for individuals struggling with conditions like arthritis. Based on data from the Canadian Institute for Health Information database, hip and knee replacements remain among the most prevalent procedures in Canada, with an annual count exceeding 138,000 surgeries and inpatient costs estimated to surpass $1.4 billion. While the majority of joint arthroplasties yield positive outcomes, a minority of patients encounter device failure necessitating revision surgeries. These instances present complex challenges and may potentially lead to health complications. Many revision surgeries arise due to prosthetic joint infections that develop between the joint prosthesis and adjacent tissue. In Canada, statistics from 2017-2018 revealed that among total knee replacements, 8.2% required revision surgeries, with 17.7% of those cases attributed to bacterial infection. Similarly, for total hip replacements, 6.9% underwent revision surgeries, with 21.2% due to infection. Infections can initiate when microorganisms are introduced to the implant's surface through direct contact, aerosol contamination, or an existing infection in the patient. These bacteria then colonize the surface, forming a biofilm that is difficult to eradicate, largely due to the production of extracellular polymeric substances that act as a protective barrier against the body's immune response and external agents like antibiotics. Despite the availability of treatment methods for prosthetic joint infections, such as antibiotic therapy and surgical intervention like one or two-stage arthroplasty, these approaches are complex and costly. They often entail prolonged hospital stays, extensive antibiotic courses, and multiple re-operations, particularly in cases involving multi-drug resistant bacteria. This thesis aims to investigate antibacterial coatings as a preventive measure against prosthetic joint infections and bacterial proliferation in general. When a patient develops a bacterial infection, it often creates an acidic microenvironment. In response, we propose the development of pH-sensitive coatings that can be triggered by these acidic conditions. Consequently, these coatings will release antibacterial agents, facilitating the eradication of bacteria. Additionally, we introduce temperature-sensitive coatings that can respond to heat generated by inductive heating. Once the temperature surpasses 38 °C, drug release will be initiated, allowing for a bactericidal effect. These stimuli-responsive coatings will undergo evaluation to assess their degradation profiles, drug release kinetics under varying pH conditions, antibacterial efficacy, and other relevant coating properties.
Recommended Citation
Vasquez Pena, Monica, "Stimuli-responsive antibacterial coatings" (2024). Electronic Thesis and Dissertation Repository. 10039.
https://ir.lib.uwo.ca/etd/10039