An overview of modern-day technology addressed to organs-on-a-chip

Updated: Jul 10

-by Derniza Cozorici.


Following the breakthroughs in microfluidics and lab-on-a-chip technology, a novel biomedical use for microfluidic-based devices has developed in recent years, with the creation of 3D cell culture microdevices. These microfluidic devices, known as organs-on-a-chip, are platforms that simulate the in vivo microenvironment of living organs and provide more physiologically appropriate in vitro models of human organs [1].

Human physiology has long been an essential part of scientific study in order to understand diseases mechanisms, apply and develop innovative therapeutics for the vast array of disorders that exist. Microfluidic technology has shown to be a remarkable tool for simulating human organs through cultivating living cells in chambers with micrometric dimensions that are continually perfused in order to replicate physiological processes of tissues and organs [2]. This is evidenced by the vast quantity of researches that exists in the subject of organs-on-a-chip, as well as the fact that organs on chip technology is being already assessed by the pharmaceutical sector [3].

The concept is to intently reflect microenvironments of real organs, and quantity of research have focused simulating lung-on-a-chip [4], brain-on-a chip [5], liver-on-a-chip [6], kidney-on-a-chip [7] and heart-on-a-chip [8].

The organs-on-a-chip concept aims to achieve lofty objectives such as speeding medication development and minimizing animal testing. It is commonly recognized that animal models have long been used in medical research, particularly when determining the safety of novel medications for human use. Animal models, on the other hand, frequently produce erroneous predictions, and testing on large numbers of animals entails substantial time and resource constraint. Furthermore, the use of animals in clinical research is fraught with ethical conundrums. This is where the technology of organs on a chip arises. By growing human cells on miniature devices with microfluid channels, researchers may recreate the physiological conditions of human organs. These microchannels allow cells to interact by exchanging chemical signals, exactly like in human bodies [9].

Organ-on-a-chip yield could be useful for generating models for complicated diseases by studying different organ functions on a chip. This is commonly referred to as "disease-on-a-chip".


Disease-on-a-chip


Microfluidic devices of tremendous medical value might provide a greater knowledge of the metastatic cascade, notably regarding the extravasation to a specific organ, in order to stimulate the development of novel therapeutic options, thereby boosting cancer survival rates. In this regard several microfluidic approaches have been designed to explore cancer cell invasion and migration from a primary location, cell transition consequence across mechanical barriers, intravasation, adhesion, and extravasation processes, and so on [10], [11].

Organs-on-a-chip have been employed in the latest years to simulate a wide range of diseases covering nearly all organs in order to gain a new understanding of the molecular and cellular basis of various physiological and pathophysiological mechanisms, and to model various drug delivery strategies. In a recent study, a group of researchers attempted for the first time to develop a human alveolar infection model by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) using an organ chip, which enables the reproduction of lung injury and immune response to viral infection in vitro at the organ level. This organ-on-a-chip platform can accurately mimic human-relevant responses to SARS-CoV-2 infection, providing a unique platform for COVID-19 research and medication development, which can have great importance in the pandemic context [12].


Personalized medicine


It has been stated that organs-on-a-chip can also be used to tailor disease models based on patient characteristics. Organs-on-a-chip systems can in precept be designed to mirror patients physiology, for instance through which includes blood samples, primary human tissue, and cells derived from triggered pluripotent stem cell-derived cells, in addition to by tuning important physico-chemical parameters of the cell culture microenvironment primarily based on personal health data [13]. Personalized organs on chips might aid researchers in the development of novel treatments for a wide range of uncommon and underserved diseases for which current models either do not exist or are imprecise, especially when these platforms include a patient's cells, resulting in patient-specific discoveries. As an example, Tanmay Mathur, doctoral scholar in Abhishek Jain’s lab withinside the Department of Biomedical Engineering at Texas A&M University, is developing customized blood vessels to enhance expertise and derive therapies in opposition to the vascular disorder visible in sickle cell disorder and different rare illnesses of the blood and vessels [14].


How are these small devices made?


To date, numerous technologies, like as photolithography, xerography, and soft lithography, have been used to fabricate various organs-on-a-chip. With the rising interest in additive manufacturing, multiple researches have reported the fabrication of organs-on-chips with microfluidic channels using 3D printing and 3D bioprinting as well.

There are several materials that are used in the manufacturing of organ-on-a-chip devices. The proper material must meet certain requirements, such as optical transparency, gas permeability, cell non-toxicity and affordability. Starting with glass and silicon as the earliest materials utilized, various elastomers and thermoplastic polymers are currently used and studied for the fabrication of organs-on-a-chip.


Limitations and Future perspectives


Notwithstanding the cutting-edge advances in organ-on-a-chip microfluidics devices, they are not yet capable of replacing animal testing in drug development applications. The main challenges to adoption include engineering constraints, biological assay output and the cost of manufacturing.

The ultimate objective of organ-on-a-chip technology is to merge several organs into a single chip and develop a more complicated multi-organ chip model, eventually attaining "human-on-a-chip".


References

[1] N. Azizipour, R. Avazpour, D. H. Rosenzweig, and M. Sawan, “Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip,” pp. 1–33, 2020.

[2] S. N. Bhatia and D. E. Ingber, “Microfluidic organs-on-chips,” Nat. Biotechnol., vol. 32, no. 8, pp. 760–772, 2014, doi: 10.1038/nbt.2989.

[3] P. Vulto and J. Joore, “Adoption of organ-on-chip platforms by the pharmaceutical industry,” Nat. Rev. Drug Discov. 2021 2012, vol. 20, no. 12, pp. 961–962, Oct. 2021, doi: 10.1038/s41573-021-00323-0.

[4] A. Jain et al., “Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics,” Clin. Pharmacol. Ther., vol. 103, no. 2, pp. 332–340, 2018, doi: 10.1002/cpt.742.

[5] S. Dauth et al., “Neurons derived from different brain regions are inherently different in vitro: A novel multiregional brain-on-a-chip,” J. Neurophysiol., vol. 117, no. 3, pp. 1320–1341, Mar. 2017, doi: 10.1152/JN.00575.2016/SUPPL_FILE/SUPPLEMENTAL_TABLE_3.XLSX.

[6] J. Deng et al., “A liver-on-a-chip for hepatoprotective activity assessment,” Biomicrofluidics, vol. 14, no. 6, 2020, doi: 10.1063/5.0024767.

[7] L. Yin et al., “Efficient Drug Screening and Nephrotoxicity Assessment on Co-culture Microfluidic Kidney Chip,” Sci. Reports 2020 101, vol. 10, no. 1, pp. 1–11, Apr. 2020, doi: 10.1038/s41598-020-63096-3.

[8] H. Liu et al., “Heart-on-a-Chip Model with Integrated Extra- And Intracellular Bioelectronics for Monitoring Cardiac Electrophysiology under Acute Hypoxia,” Nano Lett., vol. 20, no. 4, pp. 2585–2593, Apr. 2020, doi: 10.1021/ACS.NANOLETT.0C00076/SUPPL_FILE/NL0C00076_SI_001.MP4.

[9] J. Zhu and J. Zhu, “Application of Organ-on-Chip in Drug Discovery,” J. Biosci. Med., vol. 8, no. 3, pp. 119–134, Mar. 2020, doi: 10.4236/JBM.2020.83011.

[10] D. Wlodkowic and J. M. Cooper, “Tumors on chips: Oncology meets microfluidics,” Curr. Opin. Chem. Biol., vol. 14, no. 5, pp. 556–567, 2010, doi: 10.1016/j.cbpa.2010.08.016.

[11] S. Bersini et al., “A microfluidic 3D invitro model for specificity of breast cancer metastasis to bone,” Biomaterials, vol. 35, no. 8, pp. 2454–2461, 2014, doi: 10.1016/j.biomaterials.2013.11.050.

[12] M. Zhang et al., “Biomimetic Human Disease Model of SARS-CoV-2-Induced Lung Injury and Immune Responses on Organ Chip System,” Adv. Sci., vol. 8, no. 3, p. 14, Feb. 2021, doi: 10.1002/ADVS.202002928.

[13] A. Van Den Berg, C. L. Mummery, R. Passier, and A. D. Van der Meer, “Personalised organs-on-chips: functional testing for precision medicine,” Lab Chip, vol. 19, no. 2, pp. 198–205, 2019, doi: 10.1039/c8lc00827b.

[14] T. Mathur, J. J. Tronolone, and A. Jain, “Comparative analysis of blood-derived endothelial cells for designing next-generation personalized organ-on-chips,” J. Am. Heart Assoc., vol. 10, no. 22, p. 19, Nov. 2021, doi: 10.1161/JAHA.121.022795.

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