Introduction:
Many previous approaches have been made as an advancement in the normal biological functioning of the body, having limited physiological functioning. Microfluidics is a new form of technology in bioengineering that provides new options to overcome the problems faced in medicine. These microfluidics handle smaller volumes of fluids that may be used in various clinical conditions. Using organs-on-a-chip allows for the development of smaller functional units of one or more organs. The kidneys-on-a-chip has been developed through a fusion of renal tubular cells working with microfluidic devices. Although many studies have been performed to determine the efficiency of kidneys on a chip, it still shows a very promising outcome.
What Is a Microfluidic?
Microfluidics, in general, is the process of controlled movement of fluids in smaller (submillimeter) units. Microfluidic measurement microscale devices are also occasionally called lab-on-a-chip technologies or small comprehensive analytical systems (devices used for measuring). Over several years, many new technologies proved to be more efficient than the conventional methods, mimicking technologies such as organ-on-a-chip, surface tension-assisted immunoassays, and paper-based diagnostic instruments.
What Is Organ-on-Chip Technology?
Compared to cells cultivated in dishes, organ-on-a-chip is a microfluidic method of a cell culture system that provides a much more accurate physiological version of the organ. Here, some main features include frequently infused compartments with living cells arranged in a pattern to mimic the physiology of tissues and organs. Various individual organs on chips have been created so far, including kidneys on chips, intestines on chips, livers on chips, blood vessels like the arteries and veins on chips, lungs on chips, cancer on chips, bone marrow on chips, etc. Moreover, many attempts have been made to combine numerous organs on a chip, such as the kidney, liver, intestines, and skin, or organs like the liver, bone marrow, or tumor. However, the design of these devices is based on a very particular microenvironment that is very specific to the individual organs, where the development of organs on a chip requires a lot of hard work, an adequately clean environment, and advanced learning skills.
What Is Kidney-on-Chip Technology?
With organ-on-a-chip technology, specific parts of the nephron, including the glomerulus, the distal and proximal tubule, and the medullary collecting duct, have been successfully replicated. These models have great potential for improving the nature of the existing living tissue, testing for drug toxicity, and improvising treatment methods like dialysis, which replace kidney function. To improve metabolic and endocrine functioning, the primary renal epithelial cell types found in the healthy tissue of the kidney are used for cultivation. Here, a renal tubular environment is mimicked outside the body, where the flow in microfluidic systems can promote cell polarization (conduction of electric signal of the cells) and improve function. This is how the cell-based microphysiological systems have been used to generate tissue models with disease, pathophysiology, and normal kidney function. This technology also overcomes the limitations faced in the 2D cell culture methods. It can also be used to analyze the relationship between drugs and chemicals causing nephrotoxicity (a clinical condition affecting the normal functioning of the kidney due to the damage from drugs and their chemicals. The original human cells, called human proximal tubule epithelial cells (hPTECs), are widely used in these kinds of models outside the body. However, harvesting these cells often becomes difficult within a limited number of people used as control groups in studies.
What Are the Materials Used in Kidney-on-Chip Technology?
Polydimethylsiloxane (PDMS) is a material that is frequently used to create microfluidic devices. It is inexpensive, has a long shelf life with good blood and biocompatibility, has a high gas permeability, and is extremely sensitive to chemicals. However, the capacity of PDMS to absorb hydrophobic materials limits its application in microfluidic drug testing systems. Because of this, thermoplastic polymers like polystyrene, polycarbonate, and poly(methyl methacrylate) that absorb hydrophobic substances minimally are commonly used to make these biochips. To better replicate the normal physiological process, a number of both natural and synthetic polymer-based hydrogels are added to both PDMS- and non-PDMS-based microfluidic devices.
The microfluidic bioreactor (a machine used for creating biochips) is implanted with the human epithelial cells of the kidney and MDCK (a material composed of polycarbonate membranes coated with type IV collagen). A thorough assessment of the renal epithelial cell growth, transepithelial electrical resistance, and integrity between the tight junction were all assessed using the integrated electrodes in these bioreactors. After a disruption in tight junctions was noticed, the transepithelial electrical resistance was seen to decline, and this was noticed to be in connection with a change in the transport of inulin, which was the marker used in this research.
What Is the Kidney Structure Built in Kidney-on-Chip Technology?
The renal system in humans comprises various cell types and functional units. Therefore, a biologically mimicking kidney-on-a-chip must have the dynamics of the flow of fluid, metabolic and endocrine functions of the cells, the structural arrangement of the tubular segment of the kidney, electrochemical reactions between the cells along with the osmotic pressure gradients, and cell-cell interactions, such as those between glomerular vascular endothelial cells and podocytes, so that It is considered to the physiologically similar. So far, on-chip technology has been used to construct glomerular, proximal tubular, and distal tubular physiology models. However, It is still challenging to integrate these elements in the creation of a real kidney-on-a-chip.
By studying the structure of the kidney on a chip, the function of these newer on-chip kidneys can be divided based on their parts, and they include:
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Proximal tubules on a chip.
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Glomerulus on a chip.
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Distal tubules on a chip.
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Entire kidney on a chip.
How Is Kidney-on-Chip Technology Clinically Applied?
The clinical application of such advanced technology is slowly seen to creep into different functions of the kidney, and they include:
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Treatments for Renal Replacement: Even though they are often life-saving, the usual hemodialysis treatments only approximate renal function in a harsh way, and the death rates associated with such dialysis have remained constant for decades now. Here, hemodialysis depends on a one-way diffusion and its approach towards a relatively nonselective semipermeable membrane to very prominent small and medium-sized molecules, that is in contrast to the normal functioning nephron, which filters and secretes toxins while reabsorbing small molecules and essential electrolytes. Here, the traditional dialysis filters have been modified to resemble the actual function of the nephron better.
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Drug Research and Development: Previously, drugs that alter renal blood flow have been difficult to screen for nephrotoxicity outside the body. These compounds and inhibitors of calcineurin are examples of vasoconstrictors that decrease oxygen delivery and harm the renal medulla. The on-chip models may soon be accessible to resemble vasoconstrictive nephrotoxicity. However, recently developed blood vessel-on-a-chip devices have shown that vasoconstrictive behaviors can be used to examine organ-on-chip models.
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Both Advantages and Disadvantages: Microfluidic devices allow different cell types to coexist and are vital for looking into warning signs, cell recruitment, and cell-cell interactions in healthy and sick conditions. Moreover, the inclusion of sensors into microfluidic systems enables continuous monitoring of cellular activities. Apart from using electrodes to track the strength of the epithelial barrier by transepithelial (within the cells) electrical resistance measurements, the on-chip systems having massive spectrometric analysis embedded allow the analysis of proteomic, metabolomic, and genomic fingerprints in reaction to certain stimuli and substances. Combining data transfer technology with on-chip devices is believed to enhance cellular monitoring and prediction of a toxic model.
Conclusion:
This on-chip technology results from advancements in renal cell-seeded hollow fiber devices and a model of a wider spectrum of kidney activities. Such methods could be useful in predicting the idea of expecting drug toxicity and in vitro (outside the body) human kidney disease models. Many patients could be prevented from the potentially fatal consequences of unexpected reactions as a side effect, and the expenses of developing new medications could be significantly decreased. Research on kidney diseases, which are associated with significant worldwide costs for society and human health, including their causes and treatment, could be made easier by these technologies.
