Tissue engineering scaffolds consist of pores lined with cells through which a nutrient-filled fluid passes. Over time, cells consume the nutrients and proliferate, causing the pores to shrink until they completely fill with tissue. Existing literature has investigated the effects of nutrient flow rate, nutrient concentration, cell hunger rate, scaffold elasticity, and shear stress on cell proliferation within cylindrically shaped pores. In this work, we aim to model tissue growth considering all factors simultaneously while utilizing a different scaffold geometry. Specifically, we consider a branching structure; a scaffold which begins as a cylinder but repeatedly bifurcates over the length of the scaffold. Our objectives are the following: (i) develop a model of cell proliferation which includes nutrient flow dynamics and concentration, cell hunger, and scaffold elasticity; (ii) solve the model and then simulate the cell proliferation process; and (iii) optimize the initial configuration of the scaffold channels to maximize the cell growth. The results of this study are key to adapting the equations governing cell proliferation to more complex geometries, ones which can more accurately represent scaffolds used in experimental tissue engineering.

Chronic Pseudomonas aeruginosa infections are the hallmark of late-stage lung disease in individuals with cystic fibrosis. During chronic infection, P. aeruginosa becomes the dominant bacteria in the airway. Within-host adaptation of P. aeruginosa leads to vast phenotypic and genetic population heterogeneity. In vitro studies show mutations in lipopolysaccharide (LPS) O-specific antigen changes the aggregate formation in P. aeruginosa, however role of these changes in aggregate assembly in vivo is not understood. Using a synthetic CF sputum media and a preclinical murine infection model we assessed how the PAO1 wildtype and O-specific antigen mutants interact with each other, and if P. aeruginosa population heterogeneity affects the colonization of the murine lungs. Our findings suggest that the presence of variants lacking O-specific antigen does not impact the population fitness and size in both in vitro and in vivo, however it can influence the aggregate volume in vivo.

Arenaviruses are segmented negative-strand RNA viruses listed as highly pathogenic and as potential pandemic threats by the Center for Disease Control and Prevention (CDC) and the World Health Organization (WHO). They cause severe hemorrhagic fevers, including Lassa fever (case fatality rate up to 15%) and Bolivian hemorrhagic fever ( 35% case fatality rate). Currently, no effective vaccines or specific treatments exist, except for limited efficacy of ribavirin treatment in early stages. Therefore, developing potent inhibitors against these viruses is crucial. A key mechanism employed by arenaviruses to invade host cells is "cap snatching." This process involves stealing the 5' cap structure from host mRNAs, enabling the viral RNA-dependent RNA polymerase (RdRp) to initiate viral mRNA synthesis to replicate the negative-sense genome. Our lab aims to develop effective antiviral treatments against arenaviruses by targeting their cap snatching mechanism. Through endonuclease enzyme inhibition studies, we have identified novel and promising compounds that will be further optimized through X-ray crystallography and other studies for potential drug development. We thank our collaborators in The Midwest Antiviral Drug Discovery Center (AViDD) for the partnership and support. This work is supported by an NIH grant (1U19AI171954 - 01) and a CDT/GSU fellowship to Oluwafoyinsola O. Faniyi.