Drug discovery and toxicology are complex and highly depend on animal testing which often fails to predict human trial outcomes due to species differences. Coupled with ethical concerns around animal testing, this leads to high demand for improved in vitro cell culture platforms. Achieving physiologically relevant in vitro human organ models for a reliable assessment of the physiological responses of the body to drug compounds and toxins is challenging. The latest development in in vitro cell culture models, organ-on-chips (OOCs), seeks to introduce more realistic models of organ function. Current OOCs often use commercial porous polymeric membranes as a barrier membrane for cell culture which is challenging due to the poor
replication of the physiological architectures. Better recapitulation of the native basement membrane (BM) characteristics is desirable for remodelling physical (e.g. intestine, skin and lung) and metabolic (e.g. liver) barrier models. Electrospinning is a polymer processing
technique capable of producing membranes with nano to micron-scale in diameter fibres which have the potential to replicate the fibrillated architecture of the basement membranes. This thesis looks at the development of lung BM mimicking constructs utilising electrospinning
regarding ultrastructural and mechanical characteristics. The electrospinning process was first optimised regarding the solvent selection (theoretically & experimentally) and the processing
parameters (using Response Surface Methodology) to achieve electrospun membranes with properties correlating to those of the native BM. Biological studies confirmed the formation of a stable in vitro alveolar model assessed by the formation of confluent layers of human lung carcinoma epithelial cells (A549) and human pulmonary microvascular endothelial cells (hPMEC) on the opposite sides of the selected membrane as relevant cells to those of the alveolar-capillary barrier in the lung. The membrane can be easily adapted to other barrier tissue models due to the great similarity of the BM as their core structure