Controlled release of therapeutics from orthopaedic implants

King, David James (2020) Controlled release of therapeutics from orthopaedic implants. PhD thesis, University of Glasgow.

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Abstract

The scientific literature contains a variety of experimental studies centred on the theme of drug delivery from orthopaedic implants (OIs). These experiments cover a wide range of ideas, including the design of novel implant coatings to contain and control drug release; fabrication and testing of prototype drug-filled devices and; preliminary investigations into the effect of the drug when released into the biological environment. There are a multitude of issues that arise from the use of OIs and of these, the problem of orthopaedic associated infection receives particular attention. A key challenge is the prevention of bacterial infection in order to avoid the failure of the associated implant-a serious complication for patients and a significant burden on health care provider resources. A mathematical study is presented in this thesis which covers a wide variety of topics: ranging from a more fundamental investigation into the use of porosity to control the delivery of drug through to more practical modelling of two seemingly similar prototype orthopaedic fixation pins that have vastly different drug release properties. A common theme is the consideration of how experimental conditions shape the outcome of the experiment and indeed the mathematical model adopted. In order to be able to effectively control the release of drug from an orthopaedic implant, one has to have sufficient knowledge of the purpose of the drug: this determines the required dose and release rate. Thus, towards the end of the thesis, a gradual investigation of the growth of bacteria subject to antibiotic release from the aforementioned pins is carried out, to model the interplay between the two processes.

There are several conclusions that arise from the research contained within this thesis. These include: there exists little-to-no mathematical modelling in the field of drug release from OIs; porosity is likely a very fruitful approach to control the release of a drug from an OI; the conditions in which an experiment is carried out is crucial; the dissolving process of a drug is an important process and one that may be the governing means of limiting the rate of drug release; the use of 1D modelling is sometimes sufficient to answer key questions; there is a need for collaborative efforts between mathematicians and experimentalists for the goal of effective drug-releasing OIs to be realised and; the desired outcome, where infection is concerned, is highly dependent on the drug release profile and, critically, the implant surface concentration of, and potency of, the antibiotic delivered.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: orthopaedic implants, drug release, mathematical modelling, infection, bacterial growth.
Subjects: Q Science > QA Mathematics
Colleges/Schools: College of Science and Engineering > School of Engineering > Biomedical Engineering
Supervisor's Name: McGinty, Dr. Sean
Date of Award: 2020
Depositing User: Dr David James King
Unique ID: glathesis:2020-81530
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Jul 2020 05:39
Last Modified: 27 Jul 2020 05:43
URI: http://theses.gla.ac.uk/id/eprint/81530
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