Advanced in vitro testing strategies to understand the lung cell-(nano)particle interaction at the air-blood barrier

Abstract: The lung represents the primary exposure route to the human body for any sized particle. In the past three decades, the implications of exposure to nano-sized particles has received increased focused in regards to human health due to the increase in nanotechnology-related applications being manufactured. Concomitant with this has been the consistently heightened concerns of the ability for the nano-sized fraction of air pollution to cause the onset of, as well as exacerbate lung disease(s). Furthermore, due to the need to move away from invasive animal experimentation and develop applicable in vitro technologies, there has been increased attention given to the development of advanced models of the alveolar region of the lung, and the air-blood barrier. Most focus has been given to constructing systems based upon multiple cells, since these provide the ability to build models that exhibit anatomically correct structures. Yet, whilst these systems have been used with great effect to study the potential adverse biological impact of of nano-sized materials and provide clear advantages over monoculture systems due to cell-to-cell interplay, such systems are static and do not provide the physiological, dynamic environment of the air-blood barrier in vivo. Models focussing on the dynamic movement and fluid-flow are available, yet do not allow for the multi-cellular approach. Thus, the objective of this presentation is to provide a succinct overview of the above imbalance and highlight the ongoing research that we are conducting in order to close the knowledge gap and produce a dynamic functioning, multi-cellular model of the air-blood barrier to study the risk posed to human health following exposure to nano-sized particles.