Towards a stackable kidney-on-a-chip model with morphogen patterning for nephron segment differentiation
Date
2025-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Recapitulating multiple regions of the nephron remains a challenge with current
organ-on-a-chip strategies. However, patterned nephron systems can provide insight
into mechanisms of disease and induce spatially regulated differentiation of stem cells
and organoids into tissues with nephron segments. We have created three kidney-on-a chip devices with physical and chemical nephron patterning. In Aim 1, we developed a
stackable nephron-on-a-chip with hydrogel layers open on both sides of the device.
This enables the integration of multiple cell types and tissue structures by adding
layers to the system. In Aim 2, we created an external gradient generator to apply
morphogenetic gradients using source-sink diffusion to collagen-based
microphysiological systems, such as the model developed in Aim 1. In Aim 3, we
established a nephron-on-a-chip with interstitial flow patterning to apply growth factor
concentrations to defined regions along a lumenized microchannel. These systems
require optimization for longer-term cell culture, hydrogel stability, and perfusion at
incubation temperatures. Future work includes coculturing nephron cell types through
stacked tissues in the Aim 1 device. Moreover, spatially-directed nephron progenitor
cell (NPC) differentiation can be studied within the Aim 2 and Aim 3 systems.