Development of novel Staphylococcus aureus biofilm treatment: A biomaterials approach to delay antibiotic tolerance and inhibit bacterial-mediated bone destruction
Bacterial biofilms are adherent, treatment-recalcitrant communities that contribute to the chronicity of diseases such as osteomyelitis, a debilitating infection of bone that results in increased morbidity and mortality. Staphylococcus aureus is the most commonly isolated bacteria from bone and boasts an arsenal of virulence factors that contribute to devastating morbidities including bone destruction. This dissertation seeks to address innovative strategies that delay the manifestation of antibiotic-recalcitrance during biofilm formation on 3D substrates and mitigate bacterial-mediated bone loss during osteomyelitis. We detail the influence of substrate morphology on the development of antibiotic-recalcitrance within adherent bacterial communities using a novel in vitro biofilm model. Next, we discuss the utilization of polyurethane (PUR) foams for local drug delivery to demonstrate the anti-virulent activity of diflunisal, a non-steroidal anti-inflammatory drug (NSAID) in a murine osteomyelitis model. However, a significant complication of local drug delivery is the bacterial colonization of foreign materials. Therefore, we leverage diflunisal activity and a poly(propylene sulfide) nanoparticle delivery technology for hydrophobic small molecules to overcome limitations of local osteomyelitis treatment. These collective works provide novel treatment strategies and potential drug delivery platforms to progress small molecule therapy of recalcitrant infection in the bone microenvironment.