A biofilm is a community of microorganisms embedded in a matrix of polymers. The focus of this project is on biofilms that grow in the lungs of cystic fibrosis (CF) patients. A biofilm structure protects bacteria and makes it harder for natural enzymes and drugs to fight the bacteria within the biofilm. Biofilms also secrete compounds that stimulate pro-inflammatory cytokines, which further damage the underlying lung tissue.
The goal of this work is to improve the understanding of how drugs disperse through a biofilm. To accomplish this goal, a discrete model was adopted. The model describes the nutrient and biomass as discrete particles. Diffusion of the nutrient, consumption of the nutrient by microbial particles, and growth and decay of microbial particles are simulated using stochastic processes, which are directly related to physical and biological parameters of the system. These processes have been modeled previously by other authors. Our model extends the complexity of the biofilm system by including the conversion and reversion of living bacteria into a hibernated state, known as persister bacteria. Another new contribution is the inclusion of antimicrobial in two forms: an aqueous solution and encapsulated in biodegradable nanoparticles. Finally, we model bacteria movement using Monte Carlo (MC) techniques, which is unique from other discrete models. The bacteria population growth and spatial variation of drugs and their effectiveness are included in the project.
Due to the stochastic nature of the model, different initial conditions affect the quantitative results of the biofilm growth. However, qualitatively the results are similar. The minimum inhibitory concentration (MIC) of the antimicrobial is 6 μg/mL, which is consistent with continuum models and experiments. However, this may take a long time to clear the biofilm. For example, it took 8 μg/mL of antimicrobial over four days of exposure to kill all the living bacteria. The distribution of nanoparticles is approximately uniform after 4 hours from when the first nanoparticle enters the biofilm, which agrees with experimental results. A combined aqueous solution-nanoparticle treatment strategy achieves the quickest clearance of living bacteria from the biofilm.