Development of advanced healthy and diseased in vitro 3D glomerulus model for drug testing and understanding kidney disease mechanisms

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Kidney plays an important role in maintaining homeostasis in the body by regulating water, electrolytes, and the acid/base balance. Apart from secreting various hormones, it also plays an important role in regulating red blood cell production and blood pressure. For understanding kidney diseases and for drug testing it would be helpful to have functional in vitro models of the different units of the organ. Whereas a number of models for the proximal tubule have been proposed in the last years only few models for the glomerulus exist – which is the part of the kidney where primary urine is formed. Main problem is to mimic the relatively high internal pressure of capillaries which is relevant for the filtration processes.In this Indo-German project we want to use state-of-the-art additive manufacturing technologies like melt electrowriting to fabricate fibrous tubes which are able to withstand the physiological pressure. The tubes will be coated with components of the extracellular matrix (ECM) of the glomerulus like collagens and laminin and also with decellularised ECM from animal-derived kidney glomeruli. After seeding of the tubes with tissue-specific endothelial cells (lumen) and podocytes (external surface) the structures will be integrated in customised perfusion bioreactors which allow separate perfusion of both internal (tube lumen) and external spaces. Finally, the function and relevance of the model will be tested by applying known drugs.This collaborative project will combine the expertise of both applicants in the fields of biomaterials, tissue engineering and additive manufacturing (Michael Gelinsky, TU Dresden) and extraction from ECM from decellularised tissues and design and manufacturing of customized bioreactor systems (Falguni Pati, IIT Hyderabad).