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Bioengineered in vitro models of the kidney offer unprecedented opportunities to better mimic the in vivo microenvironment. Kidney-on-a-chip technology reproduces 2D or 3D features which can replicate features of the tissue architecture, composition, and dynamic mechanical forces experienced by cells in vivo. Kidney cells are exposed to mechanical stimuli such as substrate stiffness, shear stress, compression, and stretch, which regulate multiple cellular functions. Incorporating mechanical stimuli in kidney-on-a-chip is critically important for recapitulating the physiological or pathological microenvironment. This review will explore approaches to applying mechanical stimuli to different cell types using kidney-on-a-chip models and how these systems are used to study kidney physiology, model disease, and screen for drug toxicity. We further discuss sensor integration into kidney-on-a-chip for monitoring cellular responses to mechanical or other pathological stimuli. We discuss the advantages, limitations, and challenges associated with incorporating mechanical stimuli in kidney-on-a-chip models for a variety of applications. Overall, this review aims to highlight the importance of mechanical stimuli and sensor integration in the design and implementation of kidney-on-a-chip devices.
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A multi-domain shear-stress dependent diffusive model of cell transport-aided dialysis: analysis and simulation
Kidney dialysis is the most widespread treatment method for end-stage renal disease, a debilitating health condition common in industrialized societies. While ubiquitous, kidney dialysis suffers from an inability to remove larger toxins, resulting in a gradual buildup of these toxins in dialysis patients, ultimately leading to further health complications. To improve dialysis, hollow fibers incorporating a cell-monolayer with cultured kidney cells have been proposed; however, the design of such a fiber is nontrivial. In particular, the effects of fluid wall-shear stress have an important influence on the ability of the cell layer to transport toxins. In the present work, we introduce a model for cell-transport aided dialysis, incorporating the effects of the shear stress. We analyze the model mathematically and establish its well-posedness. We then present a series of numerical results, which suggest that a hollow-fiber design with a wavy profile may increase the efficiency of the dialysis treatment. We investigate numerically the shape of the wavy channel to maximize the toxin clearance. These results demonstrate the potential for the use of computational models in the study and advancement of renal therapies.
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- Award ID(s):
- 2012686
- PAR ID:
- 10328737
- Date Published:
- Journal Name:
- Mathematical Biosciences and Engineering
- Volume:
- 18
- Issue:
- 6
- ISSN:
- 1551-0018
- Page Range / eLocation ID:
- 8188 to 8200
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3934/mbe.2021406
