Mathematical modelling of antibiotic release from medical implants to counteract biofilm formation

Mandal, Parna (2025) Mathematical modelling of antibiotic release from medical implants to counteract biofilm formation. PhD thesis, University of Glasgow.

Abstract

A biofilm is a community of bacteria embedded in a self-produced extracellular matrix (EPS) that adheres to surfaces like medical implants. Biofilms are highly resistant to antibiotics due to the protective EPS barrier and dormant persister cells, leading to chronic infections that are difficult to eradicate and often require surgical intervention. This resistance, along with the increase in antibiotic resistant bacteria, underscores the need for new strategies to manage biofilm-related infections. This thesis aims to address this challenge by investigating the dynamics of biofilm growth under various conditions, including nutrient availability and antibiotic exposure. The goal is to provide insights for developing more effective therapeutic strategies. A simple mathematical model of biofilm growth is introduced, progressively incorporating complexities such as different bacterial phenotypes, nutrient-dependent transition rates between proliferative and persister bacteria, and controlled antibiotic release from porous implant. Before exploring the mathematical models in detail, this thesis introduces a hierarchy of adaptable models tailored to the needs of different studies.

The key findings of this thesis reveal the critical role of nutrient availability and antibiotic distribution in controlling biofilm growth. In nutrient-rich environments, biofilms grew rapidly but were more vulnerable to collapse under antibiotic treatment, while nutrient-poor conditions promoted persister cells, leading to thinner and more resilient biofilms that were harder to eliminate. Controlled antibiotic release from porous implants provided initial biofilm suppression but was insufficient for long-term control without sustained release, as biofilms regrew after antibiotic depletion. It is also clear from the results that higher initial antibiotic concentrations delayed biofilm regrowth but did not ensure complete eradication. Finally, spatially optimised antibiotic loading, which has a higher antibiotic concentration near the implant-biofilm interface, worked better for short-term suppression but resulted in poorer long-term biofilm control. In contrast, distributing the antibiotic farther from the implant-biofilm interface led to more sustained suppression over time. These findings underscore the need for strategies that balance sustained antibiotic presence with nutrient manipulation for effective biofilm control in clinical settings.

This work lays the foundation for several future avenues in optimising antibiotic delivery, including spatially variable implant porosity, pulse dosing, and systemic administration. The final model can also be extended to include environmental factors such as temperature and pH and can be expanded to higher-dimensional biofilm structures.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QA Mathematics; Q Science > QR Microbiology
• Colleges/Schools: College of Science and Engineering > School of Mathematics and Statistics
• Funder's Name: Engineering and Physical Sciences Research Council (EPSRC)
• Supervisor's Name: Mottram, Professor Nigel and McGinty, Dr. Sean
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85250
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 24 Jun 2025 13:26
• Last Modified: 24 Jun 2025 13:29
• Thesis DOI: 10.5525/gla.thesis.85250
• URI: https://theses.gla.ac.uk/id/eprint/85250