Dissertation
Comparison of in vitro and in vivo models for the thermal mitigation of bacterial biofilms
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2024
DOI: 10.25820/etd.007675
Abstract
Hundreds of thousands of patients suffer annually from biofilm infections on medical implants that resist antibiotics and immune defenses. Current standard of care often necessitates multiple surgeries for implant replacement, leading to extended hospital stays, risks of reinfection, and substantial financial burdens on the healthcare system. Strategies aimed at preventing biofilm formation are hindered by limitations in implementation and efficacy. A promising alternative involves delivering heat remotely to the infected surfaces to potentially eradicate biofilms in situ. Despite promising results in laboratory settings, the effectiveness and safety of thermal treatment in vivo remains largely unexplored. This study seeks to address this gap by comparing findings from laboratory experiments with observations from in vivo trials. First, Pseudomonas aeruginosa biofilms were cultured on stainless-steel implants in a mouse model, demonstrating that in vivo biofilms exhibit lower population densities than their in vitro counterparts. Thermally treating these biofilms in vitro, through immersion in hot media, revealed greater thermal susceptibility compared to the in vitro biofilms. Second, electro-resistive devices were developed and tailored to serve as substrates for biofilm culture and deliver controlled surface thermal shocks at the biofilm interface. In vitro cultured biofilms on these devices were implanted in mice and subjected to thermal shocks, which significantly reduced biofilm populations. However, these treatments also caused bacteria to disperse into surrounding tissues, contributing to biofilm regrowth. This highlighted the importance of combining thermal and antibiotic treatments to effectively prevent biofilm recurrence. Combining thermal shocks with tobramycin showed promise for biofilm elimination and improved clinical outcomes by reducing signs of systemic infections in mice. Further evaluation of the thermal susceptibility of biofilms grown in vivo and subjected to in vivo thermal shocks provided insights into biofilm behavior in a host environment. Allowing in vitro grown biofilms to acclimate within mice adjusted their population to levels observed in in vivo grown biofilms. Additionally, treatments that eliminated in vitro biofilms when subjected to thermal shock in vivo along with tobramycin during survival surgeries appeared to have lower percentages of samples with eliminated populations. These findings may underscore the influence of host factors on biofilm responses to thermal treatment, but the limited sample size emphasizes the need for further investigation with larger-scale trials to draw robust and statistically significant conclusions. Histological analysis of mouse skin and muscle tissues across these experimental groups revealed signs of cell damage, skin burns, and tissue necrosis, predominantly observed in the survival surgeries, which appeared comparable to the inflammation and damage caused by bacterial infections alone. In contrast, tissue samples from non-survival surgeries without the presence of bacteria did not show evidence of damage, at least not beyond that caused by the surgical operation itself. Overall, these findings suggest that thermal treatment may offer an efficient and potentially less invasive therapeutic approach against biofilm infections compared to current surgical standards. This study lays the foundation for further refinement of thermal treatment approaches and larger-scale animal studies that could enhance the clinical advancement of thermal treatment as an innovative therapeutic strategy against biofilm infections on medical implants.
Details
- Title: Subtitle
- Comparison of in vitro and in vivo models for the thermal mitigation of bacterial biofilms
- Creators
- Paraskevi Konstantina Zoga
- Contributors
- Eric E. Nuxoll (Advisor)Jennifer Fiegel (Committee Member)David G. Rethwisch (Committee Member)David A. Stoltz (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemical and Biochemical Engineering
- Date degree season
- Summer 2024
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007675
- Number of pages
- xxii, 193 pages
- Copyright
- Copyright 2024 Paraskevi Konstantina Zoga
- Comment
- This thesis has been optimized for improved web viewing. If you require the original version, contact the University Archives at the University of Iowa: https://www.lib.uiowa.edu/sc/contact/
- Language
- English
- Date submitted
- 07/23/2024
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 162-173).
- Public Abstract (ETD)
Every year, hundreds of thousands of patients suffer from antibiotic-resistant biofilm infections on medical implants. Current treatments often require multiple surgeries for implant replacement, resulting in prolonged hospital stays, risks of reinfection, and significant financial burden for the healthcare system. Thermal treatment, which involves delivering remotely heat to the infected surface, has been suggested as a potential alternative, though its effectiveness in living organisms is still uncertain.
This study aims to bridge the gap between laboratory findings and animal models in the thermal treatment of biofilm infections. Initially, biofilms cultured in mice and treated thermally in the lab, through immersion in hot media, showed reduced bacterial numbers and increased sensitivity to thermal shock compared to lab-grown biofilms. Next, biofilms were grown on electronic devices heated with a resistor. Culturing these biofilms in the lab and then thermally treating them through the device’s surface, while placed within mice, resulted in significant reductions in population. However, these treatments led to bacterial spread into nearby tissues, contributing to biofilm regrowth. To address this issue, thermal treatment was combined with tobramycin, demonstrating effective biofilm elimination.
Both culturing and treating biofilms within mice, while using these devices, showed more samples with live biofilm cells compared to the previous experimental arm, but still demonstrated promising results regarding the effect of thermal treatment. This highlights the need for further, larger-scale studies to understand the role of host factors in biofilm behavior. Histological analysis revealed tissue damage from thermal treatments, comparable to the damage caused by the surgical operation and the bacterial infection alone. These findings suggest that thermal treatment shows potential as a non-invasive therapeutic strategy against biofilms, deserving further investigation.
- Academic Unit
- Chemical and Biochemical Engineering
- Record Identifier
- 9984697939902771
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