Microfluidic system for generating a three-dimensional (3D) vascularized islet-on-a-chip model

Abstract

Diabetes is a disease associated with the insufficiency of pancreatic endocrine part, consisting mainly of pancreatic islets. Currently, diabetes is considered the fastest growing civilization disease. Globally, over 440 million people suffer from diabetes, and it is estimated that this number will increase to 700 million by 2045. Pancreatic islets are complex, highly vascularized mini-organs, and only the development of a fully functional vascularized pancreatic islet model could lead to the progress of knowledge about diabetes evolution, new therapeutic strategies, and the islet generation for applications in regenerative medicine. Therefore, the main goal of our study was to develop a microfluidic system for the simultaneous culture of two three-dimensional (3D) research models. The device presented in this article was used to simultaneously culture a model of a blood vessel composed of endothelial cells (HUVEC) developed using the Viscous Finger Patterning (VFP) technique and a model of the pancreatic islet, which was developed using a co-culture of α and β cells. During the research, device production method was optimized, and for this purpose, the most precise micro-milling technique was compared with the rapid prototyping technique - 3D printing. The spatial arrangement of cells in the developed models, their morphology, and viability were visualized using fluorescence staining and confocal microscopy analysis. This article presents preliminary research to develop a long-term culture of a complex model imitating the connection between the microvessel and the pancreatic islet, which in the future will be used to develop new therapeutic strategies or generate fully functional islets.