Author ORCID Identifier:
Date of Graduation
7-2026
Document Type
Thesis
Degree Name
Master of Science in Cell & Molecular Biology (MS)
Degree Level
Graduate
Department
Cell & Molecular Biology
Advisor/Mentor
Stenken, Julie
Committee Member
Lessner, Daniel
Second Committee Member
Durdik, Jeannine
Keywords
Bacterial biofilm; Cytokines; Implant-associated infection; Macrophages; Microdialysis
Abstract
Macrophage activation is an underexplored method for combating the deleterious effects of biofilm-based implant infections. Implant-associated infections (IAIs) impose significant clinical and economic burdens with costs reaching $28.4 to $45 billion per year with nearly 100,000 deaths per year. Approximately 60-80% of implant-associated infections are due to the formation of a bacterial biofilm frequently resulting in multiple revision surgeries. This interaction between macrophages and bacterial biofilms and why macrophages accept biofilms as “host” is not well understood. Due to the possibility of using macrophage activation to defend against the bacterial cells, this research focused on using a microdialysis-based implant model to assess macrophage activation into its pro-inflammatory response and the resulting biofilm chemical response. A two-method approach was demonstrated to study the pro-inflammatory response of macrophages in a culture with a bacterial biofilm. The first approach involved priming the macrophages at the site of the microdialysis probe for their direct attachment on the membrane and confirming their polarization towards the M1 (pro-inflammatory) state. It was found that LPS can stimulate the macrophages toward an M1 state through a measured increase in CCL2, IL-8, and IL-1β concentrations. It was also found that coating the microdialysis membrane in fibrinogen and perfusing the chemokine IL-8 appears to be the most effective for macrophage attachment, although further verification via immunohistochemical staining is needed. The second approach involved priming the biofilm at the site of the microdialysis probe prior to macrophage co-culture, followed by perfusion of CCL2 to monitor the pro-inflammatory response. This approach showed that a microdialysis 3D-printed lattice for promoting biofilm attachment can be used in conjunction with the microdialysis probe, enabling facile cytokine monitoring. Though perfusing CCL2 did not alter IL-8 or IL-1β concentrations compared to controls, this implant model could be used as a drug delivery system to analyze how a drug compound may enhance biofilm disruption, while concomitantly monitoring the immune response.
Citation
Luebbert, S. M. (2026). Microdialysis-based Implant Model for Macrophage Activation and Bacterial Biofilm Disruption. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/6338