Addario, Gabriele (Maastricht University-MERLN institute)


Chronic kidney diseases (CKD) is the twelfth leading cause of death worldwide, where patients present a gradual loss/impairment in kidney function, leading to end-stage renal disease (ESD). People suffering from ESD have limited life-saving temporal renal replacements options, such as the kidney dialysis, while donor organ transplantation is still the current gold standard, generally hampered by the limited organ availability. The need of replacement therapies is being investigated worldwide. In vitro platforms to study CKD might facilitate further understanding of its progression and eventually the development of new therapies. Biofabrication approaches such as 3D printing and bioprinting offer the possibility to produce pre-designed in vitro models and potentially new therapies. Several approaches are currently under investigation, such as scaffold, stem cell based therapy and decellularised animal tissue, but these are far from being alternatives. Therefore, reliable in vitro models are clearly needed. We developed extrusion based bioprinted chip models which present multiple advantages compared to the classical microfluidic chips, in terms of reproducibility, cost, production time and feasibility of varying geometry. We used bioprinting to produce sacrificial pluronic filament structures that were subsequently encapsulated in PDMS. The pluronic was then removed, creating empty channels that were subsequently seeded with cells. Primary renal epithelial cells (keratin 8-yellow fluorescent protein, Krt8-YFP) and human umbilical vein endothelial cell (HUVEC) were used. Results showed that it was possible to bioprint channels in varying diameters. The effect of channel geometry, its reproducibility and coatings for optimal cell culture were all evaluated. Cultured Krt8-YFP and HUVEC cells adhered and proliferated until a complete lumen was formed. Our model presents single and double channels, demonstrating the capability to mimic not only the renal tubule, but also the capillary side, together with extra-cellular matrix (ECM) hydrogels dispensed in the middle of the two channel, mimicking in vitro the renal tubulointerstitium. In conclusion, we believe this tubulointerstitium model can be a first step toward the production of more complex disease models for testing new therapies for CKD.


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