Microphysiological Glomerular Filtration Barriers: Current Insights, Innovations, and Future Applications

Chronic kidney disease (CKD) affects over 850 million individuals worldwide, often progressing to stages requiring dialysis or kidney transplants. Central to kidney function is the glomerular filtration barrier (GFB), which selectively filters waste while retaining essential proteins. Traditional models, including animal studies and 2D cell cultures, fail to fully replicate the GFB's complexity, limiting CKD research. Recent developments in microphysiological systems (MPS), particularly microphysiological glomerular filtration barriers (MPGFB), provide more accurate in vitro models for studying kidney diseases and evaluating therapies. MPGFB systems use organ-on-chip technology to integrate podocytes and glomerular endothelial cells within confined microfluidic environments, closely mimicking GFB's dynamic in vivo conditions. This setup enables detailed permeability analysis, aiding in research on disease mechanisms and drug toxicity. Furthermore, using human-induced pluripotent stem cells in MPGFB platforms allows patient-specific studies, enhancing insights into genetic kidney disorders. This review first examines the GFB's structure and function, focusing on its cellular and extracellular matrix components. It then discusses biological and engineering approaches to MPGFB fabrication, covering materials, 3D design, and flow control. The review concludes with MPGFB applications in disease modeling and drug testing, and addresses improvements needed for refining MPGFB as a key tool in kidney disease research and treatment.