The glomerular filtration barrier is essential for renal function, enabling selective plasma filtration while retaining cells and large proteins. Barrier disruption reduces glomerular filtration rate and is central to chronic kidney disease. Yet advanced human models that faithfully replicate this barrier remain limited, hindering therapeutic development and bioartificial kidney design.
Building on the modular, open-access, ISO-compliant microfluidic Translational Organ-on-chip Platform pioneered by the UTwente, our unit will integrate human glomerular endothelial cells with a functional glycocalyx and GBM-mimetic substrates to replicate glomerular architecture and function. This system will support mechanistic studies and drug development while forming the basis for a scalable hemofilter module for future needle-free hemodialysis and implantable biohybrid kidneys. We will explore direct cell printing on or into the platform to accelerate fabrication, avoid conventional seeding, and improve control over cell placement and layer uniformity.
Subprojects
1. Generating glomerular-like endothelial cells with fenestrae and glycocalyx
This task focuses on the development of hiPSC-derived endothelial cells (ECs) with a glomerular phenotype, characterized by the presence of large fenestrae and a negatively charged glycocalyx. These features are essential for mimicking the filtration properties of native glomerular endothelium. The candidate will build on an established differentiation protocol for fenestrated hiPSC-derived ECs. Glycocalyx will be induced by exposure to shear stress under flow conditions.
2. Fabrication of ultrathin hemocompatible nanoporous membranes with integrated cells
With support from NXTGEN Artificial Kidney Innovation Lab, the PhD candidate will fabricate nanoporous membranes using advanced 3D bioprinting technologies. The process will involve parameter and the goal is to produce very thin, microporous/nanoporous membranes ( 50μm) compatible with microfluidic assembly, which can support perfusion and viable cell function.
3. Development of TOP-compatible flow cells with integrated living membranes
A dedicated TOP-compatible flow cell will be developed in collaboration with the Artificial Kidney Innovation Lab and UTwente. The flow cells will be designed with smooth blood flow paths and physiological shear stress levels to ensure hemocompatibility and support the endothelialized glomerular filtration barrier.
4. High-Throughput Functional Testing in TOP-Integrated Flow Cells
Integration of the modules into TOP will enable automated, real-time analysis of functional performance. Functional readouts include water transport, solute transport, barrier integrity, and morphology.
