Alveolus mimics using human pluripotent stem cells and mechanistic understanding of nanoparticles translocation through respiratory system – AvleolusMimics

We aim to develop human alveolus mimics for mechanistic understanding of nanoparticles translocation through respiratory system. Alveolar epithelial and capillary endothelial cells will be obtained by differentiating human induced pluripotent stem cells (hiPSCs) and plated on the upper and lower side of a monolayer net of crosslinked gelatin nanofibers. Afterward, this artificial pulmonary membrane will be integrated into a microfluidic device which allows exposing the alveolar epithelial layer to air and the capillary endothelial layer to the nutrient. In addition, a periodic deformation of the membrane will be generated under physiological conditions. Once optimized, the translocation processes of externally inhaled nanoparticles will be studied with human alveolus mimics. Thus, this will be based on three innovative approaches: i) An extracellular matrix-like culture support which allows a minimal exogenous material contact but a maximal cell-cell contact; ii) human alveolar epithelial and capillary endothelial cells derived from hiPSCs and iii) A microfluidic control of physiological conditions which ensures the functionality of the respiratory membrane. We believe that this in-vitro model will be unique and versatile for a number of nano-toxicology studies as well as safe development of nanomedicine. Our ultimate goal is to create a new standard in biomedical research by using hiPSC derived tissues to replace conventional animal approaches, therefore accelerating industrial applications of advanced research in biomaterials and nanotechnologies.