Hemodynamic simulation and <i>in vitro</i> 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 <i>in vivo</i> imaging based three-dimensional modeling, computational fluid dynamics simulations, and <i>in vitro</i> 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.