Hemodynamic simulation and in vitro modeling of three-dimensional glomeruli at anatomical scale.

Abstract

The glomerulus is a critical filtration unit in the kidney, yet its complex three-dimensional architecture has long hindered a comprehensive understanding of its function and regulation. Here, we present an integrated framework that combines in vivo imaging based three-dimensional modeling, computational fluid dynamics simulations, and in vitro reconstruction to elucidate the structural and hemodynamic complexity of the glomerulus. Our analyses reveal that the inherent asymmetry between afferent and efferent arterioles is critical for establishing a precise pressure-flow relationship and regulating hemodynamics. We further successfully fabricated a perfusable, anatomically accurate mouse glomerulus within a microphysiological system, demonstrating proof-of-concept for perfusion analysis and vascularization. These findings establish a transformative platform for studying glomerular diseases and pave the way for therapeutic interventions.