Development of miniaturized multi-organ human skin-vasculature-liver model on chip (SVLOC) for biological investigation of cross-talk of multiple organs

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Understanding the cross-talk of skin with other organs such as the respiratory, gastro-intestinal tract and particularly the liver, is of paramount importance. The chemical absorbed through skin may be metabolized at liver, while the affected liver may also influence the skin. The studies focused on investigating this cross-talk are limited and have produced misleading and contradictory results due to technical challenges. Due to the side effect of dermal There is an essential need to establish a novel biomimetic in vitro multi-organ model to investigate the cross-talk of skin with relevant organs. The majority of commercially available or existing in vitro skin models do not include important cell types, extracellular matrix (ECM) proteins, immune response or the barrier layer against chemical diffusion. In addition, skin biopsies used in previous models suffer from donor-specific variations. The main challenge is to develop an integrated platform that can make physiologically relevant layers of different cell types within the skin to provide a long-term functional organ under appropriate nutrient supply to all cell layers, while maintaining an air-liquid interface at the top layer. For the liver model, the current liver on chip models still lack the essential cell types and physiologically relevant structure. Additionally, since blood vessels have a close interaction with the organ systems, vascularization can improve their performance. There is still no system integrating two biomimetic functional organs (in particular skin and liver models) interconnected through vasculature. The major challenge is how to engineer the integration of vasculature to organs and how to adjust the lifetimes of different organs and vasculature. Here, we propose to develop a biomimetic skin model integrated with miniaturized liver and vasculature using microfluidic approaches. This multi-organ model can be useful to characterize cross-talk of skin and associated organs and to target several principle biological questions, such as: 1) determining the impact of the vasculature system on the lifetime and performance of multi-organs models; 2) characterizing the consumption and release of different biomarkers at each organ to identify appropriate biomarkers, and 3) developing common media for long-term co-culture of multiple organs. The proposed skin­vasculature­liver model on chip (SVLOC) will have a potential to address a pressing need for predicting the allergenic or toxic potential of novel and existing chemicals and drugs on skin, vasculature or liver.