67 Development of a Physiologically-Relevant in Vitro Model of the Lung, Incorporating Novel Peptide Hydrogels as Biomimetic Extracellular Matrix Scaffolds

Abstract

Abstract The vast number of different nanomaterials (NMs) in production and under development precludes the complete hazard assessment of each individual substance according to current regulatory standards which require long term in vivo studies. To reduce the burden of in vivo toxicity testing more physiologically relevant in vitro pulmonary models are required to predict the inhalation hazard posed by aerosolized particles, including NMs. Recently significant progress has been made in the development of multi-cell 3D models which mimic the cellular constituents of tissues and organs, few models under development concomitantly take into account the functional role of the extracellular matrix (ECM) in determining the tissue microenvironment and behaviour of cells. This project specifically aims to develop an in vitro model composed of multiple cells-types grown directly in contact with hydrogel scaffolds which mimic the ECM to better replicate the in vivo microenvironment. We hypothesize the novel addition of an ECM mimetic will influence cell phenotype and activation after exposure to NMs. Preliminary data summarising the process of model building and characterisation including selection of appropriate cell lines and gel formulations, optimisation of culture conditions and evaluation of the integrity of the hydrogel scaffolds is presented. This application of this model will then be evaluated for use in toxicology testing of NMs and predictivity of hazard compared to existing data from both simple 2D in vitro systems and in vivo toxicology studies. In future the potential advantages and limitations of the approach will be evaluated and relevant adaptions to be further explored.