Preparation of 3D Zonal and Interactional Glomerular Models Based on Composite Core–Shell Hydrogel Microspheres

Abstract

Herein, to tackle the current issue of ignoring cell interactions and spatial heterogeneity in in vitro glomerulus models, a core–shell composite gel microsphere with interzonal intercommunication was developed. By adjusting the diameter ratio of the Dex-Alg/PEG-Alg droplet to the GelMA droplet, the size, shape, and compartment ratio of the droplet can be controlled. This setup keeps compartments separate yet interconnected, closely resembling the spatial arrangement of cells in glomeruli and their physiological state. Noteworthily, glomerular endothelial cells, which are supported by mesangial cells, form blood vessels, whereas podocytes form an epithelial barrier. Key functional proteins were increased, and electron imaging revealed the creation of the basement membrane. Moreover, Doxorubicin-treated models demonstrated enhanced cell death, podocyte loss, and kidney damage, which were reduced by dexrazoxane. Thus, we believe that in vitro 3D glomerular models with zone structures have significant potential for glomerular research.