10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Development of a Novel Biomimetic Platform for Simulating Human Respiratory Infections
David Drewry, Brian Damit, FELIX SAGE, Julia Patrone, Johns Hopkins University Applied Physics Laboratory
Abstract Number: 1385 Working Group: Bioaerosols
Abstract Airborne respiratory infections (e.g. inhalation of viruses, bacteria, or fungi) pose a serious threat to global health and current methods for studying human physiological response fall short for agents untestable on humans. Current methods used to study airborne transmission consist of aerosol deposition directly onto in-vitro cell cultures or exposure to in-vivo and ex-vivo animal models. Although used extensively, animal models are expensive and experimental results are challenging to extrapolate a human response due to anatomical and physiological differences. In-vitro models lack a realistic delivery method for bioaerosols and the benefit of multicellular and whole organisms response. This research seeks to address these shortcomings through the development of an experimental platform that provides a more realistic insight into pathogenesis and delivery of aerosol particles to human cells. The platform consists of an additive manufactured, anatomically-realistic upper respiratory tract for an average human male. The airway includes the mouth, trachea, and bronchi (to the third bifurcation) coupled with “inserts” seeded with human A549 cells. Embedded at various locations in the cast, these inserts match the natural curvature of the respiratory tract and allow for bioaerosols drawn into the platform to deposit naturally on the cells. Initially, inserts without A549 cells were subjected to bioaerosol loading to examine aerosol deposition location and to establish dose during an aerosol challenge. Airflow through the cast was representative of inhalation during light exercise. Finally, inserts were seeded with viable A549 cells and exposed to a model bacterial agent (Staphylococcus epidermidis). Infectivity was evaluated through live-dead staining and fluorescent microscopy. This type of platform is an important innovation in modeling whole-organ systems that can be paired with recent advances in bio-printing on the path to creating organotypic test beds. This will allow researchers to perform experiments that are more cost-effective, and that more faithfully represent airborne infection in humans.