| Biofilm implant-related infections represent one of the most difficult-to-treat pathologies in current healthcare systems. According to the National Institutes of Health, over 80% of infections in the human body are biofilm related. Biofilms are dynamic communities of bacterial cells that are often polymicrobial and which typically develop into three-dimensional structures that are attached to a surface. Due to the morphological, physiological and genotypic characteristics of biofilms, they are highly resistant to antibiotic therapies.;One of the most practical strategies that has been undertaken to prevent these biofilm implant-related infections has been the development of active release coatings on biomaterial devices. Unfortunately, to date, active release coatings have had limited in vivo and clinical success due to several important limitations.;To address these limitations, the work that was performed in this dissertation has led to or may lead to five areas of development that have the potential to contribute to the fields of bioengineering and biofilm research. First, a membrane biofilm reactor was developed to grow biofilms for use as initial inocula both in vitro and in vivo. Second, in contrast to the common use of planktonic bacteria for in vitro and in vivo testing, all aspects of this project used well-established biofilms of methicillin-resistant Staphylococcus aureus using the membrane biofilm reactor to more closely model the phenotype of bacteria that reside in natural ecosystem. Third, a novel antimicrobial compound was used as an active release agent. Fourth, the in vitro work performed in this study was done using a flow cell system to more closely model an in vivo paradigm. Fifth, the animal model that was established for this project presents the first animal model in the published literature to use well-established biofilms of MRSA that were grown under fluid sheer forces as initial inocula in an animal model of biofilm-related infection.;The in vitro results demonstrated that the active release coating was able to significantly eradicate biofilms within a 24-hour period. These results translated to the in vivo model wherein the active release coating was able to prevent biofilm implant-related infection in 100% of animals tested. Taken together, these results provide a promising outlook for the future use of this active release coating to prevent biofilm implant-related infections. |
