Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Engineering Science

Program

Biomedical Engineering

Collaborative Specialization

Musculoskeletal Health Research

Supervisor

Gillies, Elizabeth

Abstract

The clinical effectiveness of orthopedic devices to restore the function of joints has been well established yet there is a lack of development in associated infections. As the demand for orthopedic surgeries continues to rise, infection remains a growing problem and one of the main reasons for revision surgeries. Bacterial contamination of the surgical site followed by adhesion of bacteria onto the surface of orthopedic devices leads to the formation of a biofilm which is a common initiator for infection. As a result, infection in the orthopedic field is commonly defined as orthopedic device-related infections (ODRI). There are limited options to treat ODRI, with revision surgery being the most common standard of treatment involving multiple surgeries to replace the infected component, but this approach is very expensive and can reduce the quality of life for the patient. Although the use of antibiotic carriers such as poly(methyl methacrylate) (PMMA) bone cement and calcium sulfate have shown promise, their ability to control the amount and rate of drug release remains a challenge. In this study, I have investigated a novel approach in using induction heating (IH) to not only directly kill bacteria and inhibit biofilm formation but also achieve on-demand externally triggered release of antibiotics from a poly(ester amide) (PEA) coating. The PEA coating has a glass transition temperature (Tg) of 39 °C, just above physiological temperature. I demonstrated that by heating the PEA above its Tg, either by direct heating or IH, the release of antibiotics can be accelerated due to the increased mobility of the drug in the PEA film in its rubbery state. The use of an intermittent IH protocol paired with an antibiotic-loaded PEA coating leads to a synergistic reduction in biofilm formation and live bacteria on the surfaces of the coating. This new technology provides a promising new approach to potentially prevent and treat implant-associated orthopedic infections.

Summary for Lay Audience

Orthopedic device-related infections (ODRI) have been a growing problem within the orthopedic field and are one of the major reasons for revision surgery. As the demand for hip and knee replacements continues to rise, infections near orthopedic devices will follow suit. Infections are often associated with bacteria that adhere to metallic surfaces. If left untreated, they can grow in size and complexity while acting as a protective environment for bacteria. Not only are these infections difficult to treat with antibiotics, but they can also lead to antibiotic-resistant bacteria if not properly treated. The most common treatment is a two-stage revision surgery involving multiple surgeries to replace the infected component while being administered oral or intravenous antibiotics. However, this approach is expensive and reduces the quality of life of the patient. Another method to treat ODRI is the use of antibiotic carriers which act as vehicles to release antibiotics locally in the surgical site. Although these carriers have shown promise, controlling the amount and release rate of antibiotics from these carriers over the short and long term remains a challenge.

In this study, I developed a coating that can be loaded with antibiotics and coated onto the surface of a 3D-printed titanium disc. The coating can release antibiotic slowly at normal body temperatures and more rapidly at higher temperatures. Just above body temperature, the polymer coating changes from a glassy state to a rubbery state allowing the release of antibiotic from the surface of the polymer into the surrounding environment. Higher temperatures were achieved using a device that emits a high frequency alternating magnetic field, which causes the surface of the titanium disc to heat without direct contact or heating the surrounding environment (e.g., the tissue) locally. We demonstrate that by using this heating device paired with an antibiotic-loaded coating we can either prevent or disrupt the formation of bacteria on the surface of metallic orthopedic devices which is where the infections are taking place.

In this study, I developed a coating that can be loaded with antibiotics and coated onto the surface of a 3D-printed titanium disc. The coating is able to release antibiotic slowly at normal body temperatures and more rapidly at higher temperatures. Just above body temperature, the polymer coating changes from a glassy state to a rubbery state allowing the release of antibiotic from the surface of the polymer into the surrounding environment. Higher temperatures were achieved using a device that emits a high frequency alternating magnetic field, which causes the surface of the titanium disc to heat without direct contact or heating the surrounding environment (e.g., the tissue) locally. We demonstrate that by using this heating device paired with an antibiotic-loaded coating we can either prevent or disrupt the formation of bacteria on the surface of metallic orthopedic devices which is where the infections are taking place.

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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