Construction of a Multitubular Perfusable Kidney-on-Chip for the Study of Renal Diseases.

The organ-on-chip model offers versatility and modularity of in vitro models while approaching the biological fidelity of in vivo models. We propose a method to build a perfusable kidney-on-chip aiming at reproducing key features of the densely packed segments of nephrons in vitro; such as their geometry, their extracellular matrix, and their mechanical properties. The core of the chip is made of parallel tubular channels molded into collagen I that are as small as 80 µm in diameter and as close as 100 µm apart. These channels can further be coated with basement membrane components and seeded by perfusion of a suspension of cells originating from a given segment of the nephron. We optimized the design of our microfluidic device to achieve high reproducibility regarding the seeding density of the channels and high fluidic control of the channels. This chip was designed as a versatile tool to study nephropathies in general, contributing to building ever better in vitro models. It could be particularly interesting for pathologies such as polycystic kidney diseases where mechanotransduction of the cells and their interaction with adjacent extracellular matrix and nephrons may play a key role.

Enzyme-Digested Edible Bird's Nest (EBND) Prevents UV and Arid Environment-Induced Cellular Oxidative Stress, Cell Death and DNA Damage in Human Skin Keratinocytes and Three-Dimensional Epithelium Equivalents.

The aim of this study is to investigate the repressive effects of enzyme-digested edible bird's nest (EBND) on the combination of arid environment and UV-induced intracellular oxidative stress, cell death, DNA double-strand breaks (DSBs) and inflammatory responses in human HaCaT keratinocytes and three-dimensional (3D) epithelium equivalents. An oxygen radical antioxidant capacity assay showed that EBND exhibited excellent peroxyl radical scavenging activity and significantly increased cellular antioxidant capacity in HaCaT cells. When EBND was administered to HaCaT cells and 3D epitheliums, it exhibited significant preventive effects on air-drying and UVA (Dry-UVA)-induced cell death and apoptosis. Dry-UVA markedly induced intracellular reactive oxygen species (ROS) generation in HaCaT cells and 3D epitheliums as quantified by CellROX® Green/Orange reagents. Once HaCaT cells and 3D epitheliums were pretreated with EBND, Dry-UVA-induced intracellular ROS were significantly reduced. The results from anti-γ-H2A.X antibody-based immunostaining showed that EBND significantly inhibited Dry-UVA-induced DSBs in HaCaT keratinocytes. Compared with sialic acid, EBND showed significantly better protection for both keratinocytes and 3D epitheliums against Dry-UVA-induced injuries. ELISA showed that EBND significantly suppressed UVB-induced IL-6 and TNF-α secretion. In conclusion, EBND could decrease arid environments and UV-induced harmful effects and inflammatory responses in human keratinocytes and 3D epithelium equivalents partially through its antioxidant capacity.