![]() Moreover, we summarize the current research progress on adapting microfluidic chips for constructing the urinary microenvironment. In this review, we describe the biochemical and physical microenvironment of the urinary system and explore the feasibility of microfluidic technology in simulating the urinary microenvironment and pathophysiological characteristics in vitro. However, several challenges continue to impede the development of a tissue microenvironment with controllable conditions closely resemble physiological conditions. Additionally, these models facilitate improved visualization and integration and meet the requirements of the laminar flow environment of the urinary system. Microfluidic models, based on micromachining and tissue engineering technology, can integrate pathophysiological characteristics, maintain cell-cell and cell-extracellular matrix interactions, and accurately simulate the vital characteristics of human tissue microenvironments. The urinary system, comprising the kidneys, ureters, bladder, and urethra, has a unique mechanical and fluid microenvironment, which is essential to the urinary system growth and development. In this review, we summarize HTS in 2D models and discuss recent studies that have successfully demonstrated HTS-compatible 3D models of high-impact diseases, such as cancers or cardiovascular diseases. However, for 3D models, such as 3D cell-laden hydrogels and scaffolds, cell sheets, and spheroids as well as 3D microfluidic and organ-on-a-chip systems, to replace 2D models in HTS, they must be compatible with high-throughput fabrication schemes and evaluation methods. Instead, tissue-engineered 3D models with extracellular matrix-mimicking components are destined to become the preferred in vitro systems for HTS. The most frequently-used model systems for HTS, 2D models, do not adequately model the in vivo 3D microenvironment-an important aspect of which is the extracellular matrix-and therefore, 2D models may not be appropriate for drug screening. 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.ĭuring high-throughput drug screening, in vitro models are fabricated and the effects of therapeutics on the models evaluated in high throughput-for example, with automated liquid handling systems and microplate reader-based high-throughput screening (HTS) assays. We discuss the advantages, limitations, and challenges associated with incorporating mechanical stimuli in kidney-on-a-chip models for a variety of applications. We further discuss sensor integration into kidney-on-a-chip for monitoring cellular responses to mechanical or other pathological stimuli. 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. Incorporating mechanical stimuli in kidney-on-a-chip is critically important for recapitulating the physiological or pathological microenvironment. Kidney cells are exposed to mechanical stimuli such as substrate stiffness, shear stress, compression, and stretch, which regulate multiple cellular functions. 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. Microfluidic technology shows promise for simultaneous control of multiple parameters of the microenvironment and can provide a base for scaling advanced cell-based experiments into automated high-throughput formats.īioengineered in vitro models of the kidney offer unprecedented opportunities to better mimic the in vivo microenvironment. To assess microfluidics for use in microenvironmental screening, examples and categories of micro-scale and microfluidic technology are highlighted. This paper examines microenvironmental screening in terms of outcomes and benefits, key elements of the screening process, challenges for implementation, and a possible role for microfluidics as the screening platform. Screening can be used to map combinations of cells and microenvironments to phenotypic outcomes in a way that can help develop more predictive in vitro models and to better understand phenotypic mechanisms from a systems biology perspective. The microenvironment of a cell is an organized combination of extracellular matrix (ECM), cells, and interstitial fluid that influence cellular phenotype through physical, mechanical, and biochemical mechanisms. The cellular microenvironment is an increasingly discussed topic in cell biology as it has been implicated in the progression of cancer and the maintenance of stem cells.
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