“Lung-on-a-chip” as an instrument for studying the pathophysiology of human respiration

Cover Page

Cite item

Full Text

Abstract

“Lung-on-a-chip” (LoC) is a microfluidic device, imitating the gas-fluid interface of the pulmonary alveole in the human lung and intended for pathophysiological, pharmacological and molecular-biological studies of the air-blood barrier in vitro. The LoC device itself contains a system of fluid and gas microchannels, separated with a semipermeable elastic membrane, containing a polymer base and the alveolar cell elements. Depending on the type of LoC (single-, double- and three-channel), the membrane may contain only alveolocytes or alveolocytes combined with other cells — endotheliocytes, fibroblasts, alveolar macrophages or tumor cells. Some LoC models also include proteinic or hydrogel stroma, imitating the pulmonary interstitium. The first double-channel LoC variant, in which one side of the membrane contained an alveolocytic monolayer and the other side — a monolayer of endotheliocytes, was developed in 2010 by a group of scientists from the Harvard University for maximally precise in vitro reproduction of the micro-environment and biomechanics operations of the alveoli. Modern LoC modifications include the same elements and differ only by the construction of the microfluidic system, by the biomaterial of semipermeable membrane, by the composition of cellular and stromal elements and by specific tasks to be solved. Besides the LoC imitating the hematoalveolar barrier, there are modifications for studying the specific pathophysiological processes, for the screening of medicinal products, for modeling specific diseases, for example, lung cancer, chronic obstructive pulmonary disease or asthma. In the present review, we have analyzed the existing types of LoC, the biomaterials used, the methods of detecting molecular processes within the microfluidic devices and the main directions of research to be conducted using the “lung-on-a-chip”.

About the authors

Oksana A. Zhukova

Pulmonology Scientific Research Institute; Federal Center of Brain Research and Neurotechnologies

Author for correspondence.
Email: Oksana.saprikina82@mail.ru
ORCID iD: 0000-0002-0907-0078
Russian Federation, Moscow; Moscow

Iuliia V. Ozerskaya

Pulmonology Scientific Research Institute

Email: 1759317593@mail.ru
ORCID iD: 0009-0008-4893-2735
Russian Federation, Moscow

Dmitry V. Basmanov

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine

Email: basmanov.dmitry@gmail.com
ORCID iD: 0000-0001-6620-7360
SPIN-code: 1801-6408
Russian Federation, Moscow

Vsevolod Yu. Stolyarov

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine

Email: stoliarov.viu@phystech.edu
ORCID iD: 0009-0002-9168-9378
Russian Federation, Moscow

Vladimir G. Bogush

National Research Center «Kurchatov Institute»

Email: vlbogush@mail.ru
ORCID iD: 0000-0002-7159-0381
SPIN-code: 7428-0145

Cand. Sci. (Biology)

Russian Federation, Moscow

Vladimir V. Kolesov

Kotelnikov Institute of Radio Engineering and Electronics

Email: kvv@cplire.ru
ORCID iD: 0000-0001-6427-6362
SPIN-code: 6869-1397

Cand. Sci. (Physics and Mathematics)

Russian Federation, Moscow

Kirill A. Zykov

Pulmonology Scientific Research Institute; Russian University of Medicine

Email: kirillaz@inbox.ru
ORCID iD: 0000-0003-3385-2632
SPIN-code: 6269-7990

МD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences

Russian Federation, Moscow; Moscow

Gaukhar M. Yusubalieva

Federal Center of Brain Research and Neurotechnologies; Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies; Engelhardt Institute of Molecular Biology

Email: gaukhar@gaukhar.org
ORCID iD: 0000-0003-3056-4889
SPIN-code: 1559-5866

MD, PhD

Russian Federation, Moscow; Moscow; Moscow

Vladimir P. Baklaushev

Pulmonology Scientific Research Institute; Federal Center of Brain Research and Neurotechnologies; Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies; Engelhardt Institute of Molecular Biology

Email: baklaushev.vp@fnkc-fmba.ru
ORCID iD: 0000-0003-1039-4245
SPIN-code: 3968-2971

MD, PhD, Associate Professor

Russian Federation, Moscow; Moscow; Moscow; Moscow

References

  1. Федеральная служба государственной статистики [Интернет]. Здравоохранение. [Federal State Statistics Service (Internet). Health care. (In Russ.)] Режим доступа: https://rosstat.gov.ru/folder/13721. Дата обращения: 15.12.2024.
  2. Chen L, Rackley CR. Diagnosis and epidemiology of acute respiratory failure. Crit Care Clin. 2024;40(2):221–233. doi: 10.1016/j.ccc.2023.12.001
  3. Pan H, Deutsch GH, Wert SE; Ontology Subcommittee; NHLBI Molecular Atlas of Lung Development Program Consortium. Comprehensive anatomic ontologies for lung development: A comparison of alveolar formation and maturation within mouse and human lung. J Biomed Semantics. 2019;10(1):18. doi: 10.1186/s13326-019-0209-1
  4. Lagowala DA, Kwon S, Sidhaye VK, Kim DH. Human microphysiological models of airway and alveolar epithelia. Am J Physiol Lung Cell Mol Physiol. 2021;321(6):L1072–L1088. doi: 10.1152/ajplung.00103.2021
  5. Mullard A. Parsing clinical success rates. Nat Rev Drug Discov. 2016;15(7):447. doi: 10.1038/nrd.2016.136
  6. Zhu Y, Sun L, Wang Y, et al. A biomimetic human lung-on-a-chip with colorful display of microphysiological breath. Adv Mater. 2022;34(13):e2108972. doi: 10.1002/adma.202108972
  7. Huh D, Matthews BD, Mammoto A, et al. Reconstituting organ-level lung functions on a chip. Science. 2010;328(5986): 1662–1668. doi: 10.1126/science.1188302
  8. Varone A, Nguyen JK, Leng L, et al. A novel organ-chip system emulates three-dimensional architecture of the human epithelia and the mechanical forces acting on it. Biomaterials. 2021;275:120957. doi: 10.1016/j.biomaterials.2021.120957
  9. Doryab A, Amoabediny G, Salehi-Najafabadi A. Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip. Biotechnol Adv. 2016;34(5): 588–596. doi: 10.1016/j.biotechadv.2016.02.006
  10. Jensen C, Teng Y. Is it time to start transitioning from 2D to 3D cell culture? Front Mol Biosci. 2020;7:33. doi: 10.3389/fmolb.2020.00033
  11. Wang H, Brown PC, Chow EC, et al. 3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration. Clin Transl Sci. 2021;14(5):1659–1680. doi: 10.1111/cts.13066
  12. Duval K, Grover H, Han LH, et al. Modeling physiological events in 2D vs. 3D cell culture. Physiology (Bethesda). 2017;32(4):266–277. doi: 10.1152/physiol.00036.2016
  13. Martínez-Espuga M, Mata A, Ordóñez-Morán P. Intestinal cell differentiation and phenotype in 2D and 3D cell culture models. Methods Mol Biol. 2023;2650:235–243. doi: 10.1007/978-1-0716-3076-1_18
  14. Sisodia Y, Shah K, Ali Sayyed A, et al. Lung-on-chip microdevices to foster pulmonary drug discovery. Biomater Sci. 2023;11(3):777–790. doi: 10.1039/d2bm00951j
  15. Zhu L, Zhang J, Guo Q, et al. Advanced lung organoids and lung-on-a-chip for cancer research and drug evaluation: A review. Front Bioeng Biotechnol. 2023;11:1299033. doi: 10.3389/fbioe.2023.1299033
  16. Tan J, Guo Q, Tian L, et al. Biomimetic lung-on-a-chip to model virus infection and drug evaluation. Eur J Pharm Sci. 2023;180:106329. doi: 10.1016/j.ejps.2022.106329
  17. Kim HJ, Park S, Jeong S, et al. Lung organoid on a chip: A new ensemble model for preclinical studies. Int J Stem Cells. 2024;17(1):30–37. doi: 10.15283/ijsc23090
  18. Shrestha J, Razavi Bazaz S, Aboulkheyr EH, et al. Lung-on-a-chip: The future of respiratory disease models and pharmacological studies. Crit Rev Biotechnol. 2020;40(2):213–230. doi: 10.1080/07388551.2019.1710458
  19. Nawroth JC, Barrile R, Conegliano D, et al. Stem cell-based lung-on-chips: The best of both worlds? Adv Drug Deliv Rev. 2019;140:12–32. doi: 10.1016/j.addr.2018.07.005
  20. Zarrintaj P, Saeb MR, Stadler FJ, et al. Human organs-on-chips: A review of the state-of-the-art, current prospects, and future challenges. Adv Biol (Weinh). 2022;6(1):e2000526. doi: 10.1002/adbi.202000526
  21. Travaglini KJ, Nabhan AN, Penland L, et al. A molecular cell atlas of the human lung from single-cell RNA sequencing. Nature. 2020;587(7835):619–625. doi: 10.1038/s41586-020-2922-4
  22. Hartmann B, Fleischhauer L, Nicolau M, et al. Profiling native pulmonary basement membrane stiffness using atomic force microscopy. Nat Protoc. 2024;19(5):1498–1528. doi: 10.1038/s41596-024-00955-7
  23. Doryab A, Tas S, Taskin MB, et al. Evolution of bioengineered lung models: Recent advances and challenges in tissue mimicry for studying the role of mechanical forces in cell biology. Adv Functional Materials. 2019;29(39). doi: 10.1002/adfm.201903114
  24. Bai H, Ingber DE. What can an organ-on-a-chip teach us about human lung pathophysiology? Physiology (Bethesda). 2022;37(5):0. doi: 10.1152/physiol.00012.2022
  25. Whitsett JA, Weaver TE. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med. 2002;347(26): 2141–2148. doi: 10.1056/NEJMra022387
  26. Doryab A, Groll J. Biomimetic in vitro lung models: Current challenges and future perspective. Adv Mater. 2023;35(13): e2210519. doi: 10.1002/adma.202210519
  27. Shah DD, Raghani NR, Chorawala MR, et al. Harnessing three-dimensional (3D) cell culture models for pulmonary infections: State of the art and future directions. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(11):2861–2880. doi: 10.1007/s00210-023-02541-2
  28. Fang Y, Eglen RM. Three-dimensional cell cultures in drug discovery and development. SLAS Discov. 2017;22(5):456–472. doi: 10.1177/1087057117696795
  29. Morin JP, Baste JM, Gay A, et al. Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies. Xenobiotica. 2012;43(1):63–72. doi: 10.3109/00498254.2012.727043
  30. Wyss Institute. Human organs-on-chips [2021 Mar 28]. Режим доступа: https://wyss.harvard.edu/. Дата обращения: 15.12.2024.
  31. Novik E, Maguire TJ, Chao P, et al. A microfluidic hepatic coculture platform for cell-based drug metabolism studies. Biochem Pharmacol. 2010;79(7):1036–1044. doi: 10.1016/j.bcp.2009.11.010
  32. Jang KJ, Mehr AP. Hamilton GA, et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol (Camb). 2013;5(9):1119–1129. doi: 10.1039/c3ib40049b
  33. Kim HJ, Ingber DE. Gut-on-a-chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr Biol (Camb). 2013;5(9):1130–1140. doi: 10.1039/c3ib40126j
  34. Zhang W, Lee WY, Siegel DS, et al. Patient-specific 3D microfluidic tissue model for multiple myeloma. Tissue Engin Part C Methods. 2014;20(8):663–670. doi: 10.1089/ten.TEC.2013.0490
  35. Van der Meer AD, Orlova VV, ten Dijke P, et al. Three-dimensional co-cultures of human endothelial cells and embryonic stem cell-derived pericytes inside a microfluidic device. Lab Chip. 2013;13(18):3562–3568. doi: 10.1039/c3lc50435b
  36. Grosberg A, Nesmith AP, Goss JA, et al. Muscle on a chip: In vitro contractility assays for smooth and striated muscle. J Pharmacol Toxicol Methods. 2012;65(3):126–135. doi: 10.1016/j.vascn.2012.04.001
  37. Ingber DE. Developmentally inspired human ‘organs on chips’. Development. 2018;145(16):dev156125. doi: 10.1242/dev.156125
  38. Sone N, Konishi S, Igura K, et al. Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology. Sci Transl Med. 2021;13(601):eabb1298. doi: 10.1126/scitranslmed.abb1298
  39. Wang H, Yin F, Li Z, et al. Advances of microfluidic lung chips for assessing atmospheric pollutants exposure. Environ Int. 2023;172:107801. doi: 10.1016/j.envint.2023.107801
  40. Sengupta A, Roldan N, Kiener M, et al. A new immortalized human alveolar epithelial cell model to study lung injury and toxicity on a breathing lung-on-chip system. Front Toxicol. 2022;4:840606. doi: 10.3389/ftox.2022.840606
  41. Fisher CR, Mba Medie F, Luu RJ, et al. A high-throughput, high-containment human primary epithelial airway organ-on-chip platform for SARS-CoV-2 therapeutic screening. Cells. 2023;12(22):2639. doi: 10.3390/cells12222639
  42. Sengupta A, Dorn A, Jamshidi M, et al. A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip. Front Pharmacol. 2023;14:1114739. doi: 10.3389/fphar.2023.1114739
  43. Dey M, Ozbolat IT. 3D bioprinting of cells, tissues and organs. Sci Rep. 2020;10(1):14023. doi: 10.1038/s41598-020-70086-y
  44. Matai I, Kaur G, Seyedsalehi A, et al. Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials. 2020;226:119536. doi: 10.1016/j.biomaterials.2019.119536
  45. Kim W, Lee Y, Kang D, et al. 3D inkjet-bioprinted lung-on-a-chip. ACS Biomater Sci Eng. 2023;9(5):2806–2815. doi: 10.1021/acsbiomaterials.3c00089
  46. Baptista D, Moreira Teixeira L, Barata D, et al. 3D lung-on-chip model based on biomimetically microcurved culture membranes. ACS Biomater Sci Eng. 2022;8(6):2684–2699. doi: 10.1021/acsbiomaterials.1c01463
  47. Li K, Yang X, Xue C, et al. Biomimetic human lung-on-a-chip for modeling disease investigation. Biomicrofluidics. 2019;13(3):031501. doi: 10.1063/1.5100070
  48. Regehr KJ, Domenech M, Koepsel JT, et al. Biological implications of polydimethylsiloxane-based microfluidic cell culture. Lab Chip. 2009;9(15):2132–2139. doi: 10.1039/b903043c
  49. Jo BH, van Lerberghe LM, Motsegood KM, Beebe DJ. Three-dimensional micro-channel fabrication in polydimethylsiloxane (PDMS) elastomer. J Microelectromech Syst. 2000;9(1):76–81. doi: 10.1109/84.825780
  50. Gaio N, van Meer B, Quirós Solano W, et al. Cytostretch, an organ-on-chip platform. Micromachines (Basel). 2016;7(7):120. doi: 10.3390/mi7070120
  51. Bennet TJ, Randhawa A, Hua J, Cheung KC. Airway-on-a-chip: Designs and applications for lung repair and disease. Cells. 2021;10(7):1602. doi: 10.3390/cells10071602
  52. Park SE, Georgescu A, Oh JM, et al. Polydopamine-based interfacial engineering of extracellular matrix hydrogels for the construction and long-term maintenance of living three-dimensional tissues. ACS Appl Mater Interfaces. 2019;11(27):23919–23925. doi: 10.1021/acsami.9b07912
  53. Toepke MW, Beebe DJ. PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip. 2006;6(12):1484–1486. doi: 10.1039/b612140c
  54. Wang JD, Douville NJ, Takayama S, El-Sayed M. Quantitative analysis of molecular absorption into PDMS microfluidic channels. Ann Biomed Eng. 2012;40(9):1862–1873. doi: 10.1007/s10439-012-0562-z
  55. Ingber DE. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat Rev Genet. 2022;23(8):467–491. doi: 10.1038/s41576-022-00466-9
  56. Ewart L, Apostolou A, Briggs S, et al. Qualifying a human liver-chip for predictive toxicology: Performance assessment and economic implications. bioRxiv. 2021. doi: 10.1101/2021.12.14.472674
  57. Van Meer BJ, de Vries H, Firth KS, et al. Small molecule absorption by PDMS in the context of drug response bioassays. Biochem Biophys Res Commun. 2017;482(2):323–328. doi: 10.1016/j.bbrc.2016.11.062
  58. Domansky K, Leslie DC, McKinney J, et al. Clear castable polyurethane elastomer for fabrication of microfluidic devices. Lab Chip. 2013;13(19):3956–3964. doi: 10.1039/c3lc50558h
  59. Domansky K, Sliz JD, Wen N, et al. SEBS elastomers for fabrication of microfluidic devices with reduced drug absorption by injection molding and extrusion. Microfluid Nanofluid. 2017;21(6):107. doi: 10.1007/s10404-017-1941-4
  60. Schneider S, Brás EJ, Schneider O, et al. Facile patterning of thermoplastic elastomers and robust bonding to glass and thermoplastics for microfluidic cell culture and organ-on-chip. Micromachines. 2021;12:575. doi: 10.3390/mi12050575
  61. Gomez-Sjoberg R, Leyrat AA, Houseman BT, et al. Biocompatibility and reduced drug absorption of sol-gel-treated poly (dimethyl siloxane) for microfluidic cell culture applications. Anal Chem. 2010;82(21):8954–8960. doi: 10.1021/ac101870s
  62. Sasaki H, Onoe H, Osaki T, et al. Sensors and actuators B: Chemical parylene-coating in PDMS microfluidic channels prevents the absorption of fluorescent dyes. Sensors Actuators B Chem. 2010;150(1):478–482. doi: 10.1016/j.snb.2010.07.021
  63. Sicard D, Haak AJ, Choi KM, et al. Aging and anatomical variations in lung tissue stiffness. Am J Physiol Lung Cell Mol Physiol. 2018;314(6):L946–L955. doi: 10.1152/ajplung.00415.2017
  64. Polio SR, Kundu AN, Dougan CE, et al. Cross-platform mechanical characterization of lung tissue. PLoS One. 2018;13(10):e0204765. doi: 10.1371/journal.pone.0204765
  65. Kumar V, Madhurakkat Perikamana SK, Tata A, et al. an in vitro microfluidic alveolus model to study lung biomechanics. Front Bioeng Biotechnol. 2022;10:848699. doi: 10.3389/fbioe.2022.848699
  66. Mohammed MI, Haswell S, Gibson I. Lab-on-a-chip or chip-in-a-lab: Challenges of commercialization lost in translation. Procedia Technol. 2015;20:54–59. doi: 10.1016/j.protcy.2015.07.010
  67. Ongaro AE, di Giuseppe D, Kermanizadeh A, et al. Polylactic is a sustainable, low absorption, low autofluorescence alternative to other plastics for microfluidic and organ-on-chip applications. Anal Chem. 2020;92(9):6693–6701. doi: 10.1021/acs.analchem.0c00651
  68. Guan M, Tang S, Chang H, et al. Development of alveolar-capillary-exchange (ACE) chip and its application for assessment of PM2.5-induced toxicity. Ecotoxicol Environ Saf. 2021;223:112601. doi: 10.1016/j.ecoenv.2021.112601
  69. Mejias JC, Nelson MR, Liseth O, Roy K. A 96-well format microvascularized human lung-on-a-chip platform for microphysiological modeling of fibrotic diseases. Lab Chip. 2020;20(19):3601–3611. doi: 10.1039/d0lc00644k
  70. Carius P, Dubois A, Ajdarirad M, et al. PerfuPul-A versatile perfusable platform to assess permeability and barrier function of air exposed pulmonary epithelia. Front Bioeng Biotechnol. 2021;9:743236. doi: 10.3389/fbioe.2021.743236
  71. Grigoriev TE, Bukharova TB, Vasilyev AV, et al. Effect of molecular characteristics and morphology on mechanical performance and biocompatibility of PLA-based spongious scaffolds. BioNanoSci. 2018;8(4):977–983. doi: 10.1007/s12668-018-0557-9
  72. Da Silva D, Kaduri M, Poley M, et al. Biocompatibility, biodegradation and excretion of polylactic acid (PLA) in medical implants and theranostic systems. Chem Eng J. 2018;340:9–14. doi: 10.1016/j.cej.2018.01.010
  73. Ramot Y, Haim-Zada M, Domb AJ, Nyska A. Biocompatibility and safety of PLA and its copolymers. Adv Drug Deliv Rev. 2016;107:153–162. doi: 10.1016/j.addr.2016.03.012
  74. Yang X, Li K, Zhang X, et al. Nanofiber membrane supported lung-on-a-chip microdevice for anti-cancer drug testing. Lab Chip. 2018;18(3):486–495. doi: 10.1039/c7lc01224a
  75. Li W, Sun X, Ji B, et al. PLGA Nanofiber/PDMS microporous composite membrane-sandwiched microchip for drug testing. Micromachines (Basel). 2020;11(12):1054. doi: 10.3390/mi11121054
  76. Carlborg CF, Haraldsson T, Öberg K, et al. Beyond PDMS: Off-stoichiometry thiol-ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices. Lab Chip. 2011;11(18):3136–3147. doi: 10.1039/c1lc20388f
  77. Rimsa R, Galvanovskis A, Plume J, et al. Lung on a chip development from off-stoichiometry thiol-ene polymer. Micromachines (Basel). 2021;12(5):546. doi: 10.3390/mi12050546
  78. Huang D, Liu T, Liao J, et al. Reversed-engineered human alveolar lung-on-a-chip model. Proc Natl Acad Sci USA. 2021;118(19):e2016146118. doi: 10.1073/pnas.2016146118
  79. Ochs M, Nyengaard JR, Jung A, et al. The number of alveoli in the human lung. Am J Respir Crit Care Med. 2004;169(1):120–124. doi: 10.1164/rccm.200308-1107OC
  80. Zamprogno P, Wüthrich S, Achenbach S, et al. Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane. Commun Biol. 2021;4(1):168. doi: 10.1038/s42003-021-01695-0
  81. Park S, Newton J, Hidjir T, Young EW. Bidirectional airflow in lung airway-on-a-chip with matrix-derived membrane elicits epithelial glycocalyx formation. Lab Chip. 2023;23(16): 3671–3682. doi: 10.1039/d3lc00259d
  82. Licciardello M, Traldi C, Cicolini M, et al. A miniaturized multicellular platform to mimic the 3D structure of the alveolar-capillary barrier. Frontiers Bioeng Biotechnol. 2024;12:1346660. doi: 10.3389/fbioe.2024.1346660
  83. Carvalho M, Ribeiro V, Caballero D, et al. Biomimetic and soft lab-on-a-chip platform based on enzymatic-crosslinked silk fibroin hydrogel for colorectal tumor model. Authorea. 2022. doi: 10.22541/au.167232609.96998643/v1
  84. Богуш В.Г., Давыдова Л.И., Шуляков В.С., и др. Разработка биоадгезивов на основе рекомбинантных аналогов белков паутины // Биотехнология. 2021. Т. 37, № 2. С. 20–33. [Bogush VG, Davydova LI, Shulyakov VS, et al. Development of bioadhesives based on recombinant analogues of spider web proteins. Biotechnology. 2021;37(2):20–33]. EDN: ZHUEDS doi: 10.21519/0234-2758-2021-37-2-20-33
  85. Zhang Y, Wang X, Yang Y, et al. Recapitulating essential pathophysiological characteristics in lung-on-a-chip for disease studies. Front Immunol. 2023;14:1093460. doi: 10.3389/fimmu.2023.1093460
  86. Moreira A, Müller M, Costa PF, Kohl Y. Advanced in vitro lung models for drug and toxicity screening: The promising role of induced pluripotent stem cells. Adv Biol (Weinh). 2022;6(2):e2101139. doi: 10.1002/adbi.202101139
  87. Nawroth JC, Roth D, van Schadewijk A, et al. Breathing on chip: Dynamic flow and stretch accelerate mucociliary maturation of airway epithelium in vitro. Mater Today Bio. 2023;21:100713. doi: 10.1016/j.mtbio.2023.100713
  88. Heinen N, Klöhn M, Steinmann E, Pfaender S. In vitro lung models and their application to study SARS-CoV-2 pathogenesis and disease. Viruses. 2021;13(5):792. doi: 10.3390/v13050792
  89. Petpiroon N, Netkueakul W, Sukrak K, et al. Development of lung tissue models and their applications. Life Sci. 2023;334:122208. doi: 10.1016/j.lfs.2023.122208
  90. Damle EB, Yamaguchi E, Yao JE, Gaver DP. Preparation and structural evaluation of epithelial cell monolayers in a physiologically sized microfluidic culture device. J Vis Exp. 2022;(185):10.3791/64148. doi: 10.3791/64148
  91. Maoz BM, Herland A, Henry OY, et al. Organs-on-chips with combined multi-electrode array and transepithelial electrical resistance measurement capabilities. Lab Chip. 2017;17:2294–2302. doi: 10.1039/c7lc00412e
  92. Niemeyer BF, Zhao P, Tuder RM, Benam KH. Advanced microengineered lung models for translational drug discovery. SLAS Discov. 2018;23(8):777–789. doi: 10.1177/2472555218760217
  93. Yousafzai MS, Hammer JA. Using biosensors to study organoids, spheroids and organs-on-a-chip: A mechanobiology perspective. Biosensors (Basel). 2023;13(10):905. doi: 10.3390/bios13100905
  94. Kwon A, Lee NY, Yu JH, et al. Mitochondrial stress activates YAP/TAZ through RhoA oxidation to promote liver injury. Cell Death Dis. 2024;15(1):51. doi: 10.1038/s41419-024-06448-5
  95. Smirnov AV, Anisimkin VI, Shamsutdinova ES, et al. Acoustiс waves in piezoelectric layered structure for selective detection of liqiod viscosity. Sensors. 2023;23:7329. doi: 10.3390/s23177329
  96. Lee SH, Cha B, Yi HG, et al. Acoustofluidic separation of bacteria from platelets using tilted-angle standing surface acoustic wave. Sensors Actuators B Chem. 2024;417:136161. doi: 10.1016/j.snb.2024.136161
  97. Vachon P, Merugu S, Sharma J, et al. Cavity-agnostic acoustofluidic manipulations enabled by guided flexural waves on a membrane acoustic waveguide actuator. Microsystems Nanoengineering. 2024;10(1):33. doi: 10.1038/s41378-023-00643-8
  98. Huh D, Leslie DC, Matthews BD, et al. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci Transl Med. 2012;4(159):159ra147. Erratum in: Sci Transl Med. 2018;10(449). doi: 10.1126/scitranslmed.3004249
  99. Jain A, Barrile R, van der Meer AD, et al. Primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics. Clin Pharmacol Ther. 2018; 103(2):332–340. doi: 10.1002/cpt.742
  100. Hassell BA, Goyal G, Lee E, et al. Human organ chip models recapitulate orthotopic lung cancer growth, therapeutic responses, and tumor dormancy in vitro. Cell Rep. 2017; 21(2):508–516. doi: 10.1016/j.celrep.2017.09.043
  101. Benam KH, Villenave R, Lucchesi C, et al. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods. 2016;13(2):151–157. doi: 10.1038/nmeth.3697
  102. Si L, Bai H, Rodas M, et al. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat Biomed Eng. 2021;5(8):815–829. doi: 10.1038/s41551-021-00718-9
  103. Danahay H, Pessotti AD, Coote J, et al. Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung. Cell Rep. 2015;10(2):239–252. doi: 10.1016/j.celrep.2014.12.017
  104. Ordonez CL, Khashayar R, Wong HH, et al. Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. Am J Respir Crit Care Med. 2001;163(2):517–523. doi: 10.1164/ajrccm.163.2.2004039
  105. Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2006;173(10):1114–1121. doi: 10.1164/rccm.200506-859OC
  106. Jain A, van der Meer A, Papa AL, et al. Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium. Biomed Microdevices. 2016;18(4):73. doi: 10.1007/s10544-016-0095-6
  107. Сooley BC. In vivo fluorescence imaging of large-vessel thrombosis in mice. Arterioscler Thromb Vasc Biol. 2011;31(6):1351–1356. doi: 10.1161/ATVBAHA.111.225334
  108. Li L, Bo W, Wang G, et al. Progress and application of lung-on-a-chip for lung cancer. Front Bioeng Biotechnol. 2024;12:1378299. doi: 10.3389/fbioe.2024.1378299
  109. Assaad S, Kratzert WB, Shelley B, et al. Assessment of pulmonary edema: Principles and practice. J Cardiothorac Vasc Anesth. 2018;32(2):901–914. doi: 10.1053/j.jvca.2017.08.028
  110. Melencio L, McKallip RJ, Guan H, et al. Role of CD4(+)CD25(+) T regulatory cells in IL-2-induced vascular leak. Int Immunol. 2006;18(10):1461–1471. doi: 10.1093/intimm/dxl079
  111. Batool I, Qadir A, Levermore JM, Kelly FJ. Dynamics of airborne microplastics, appraisal and distributional behaviour in atmosphere: A review. Sci Total Environ. 2022;806(Pt 4):150745. doi: 10.1016/j.scitotenv.2021.150745
  112. Tokunaga Y, Okochi H, Tani Y, et al. Airborne microplastics detected in the lungs of wild birds in Japan. Chemosphere. 2023;321:138032. doi: 10.1016/j.chemosphere.2023.138032
  113. Baeza-Martínez C, Olmos S, González-Pleiter M, et al. First evidence of microplastics isolated in European citizens’ lower airway. J Hazard Mater. 2022;438:129439. doi: 10.1016/j.jhazmat.2022.129439
  114. Yang S, Zhang T, Ge Y, et al. Sentinel supervised lung-on-a-chip: A new environmental toxicology platform for nanoplastic-induced lung injury. J Hazard Mater. 2023;458:131962. doi: 10.1016/j.jhazmat.2023.131962
  115. Zhang M, Xu C, Jiang L, Qin J. A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol Res (Camb). 2018;7(6):1048–1060. doi: 10.1039/c8tx00156a
  116. Van den Berg A, Mummery CL, Passier R, et al. Personalised organs-on-chips: Functional testing for precision medicine. Lab Chip. 2019;19(2):198–205. doi: 10.1039/c8lc00827b

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig.1. The principal structure and the variants of the “lung-on-a-chip”: а — human lung acinus structure; b — schemes, developed as of today for the microfluidic devices and LoC variants (from the left side to the right: single-channel — Y. Zhu et al., 2022 [6]; double-channel — D. Huh et al., 2010 [7], three-channel — A. Varone et al., 2021 [8]); c — imitation of respiratory movements using the negative pressure in the lateral LoC channels (courtesy of D. Huh et al., 2010 [7]). ЛА — pulmonary artery; ЛВ — pulmonary vein; ГВ — smooth-muscle fibers; АМе — alveolar sac; ЛК — pulmonary capillaries; АI — type I alveolocyte; AII — type II alveolocyte; АМ — alveolar macrophage.

Download (1MB)
Indexing metadata
3. Fig.2. Methods of “lung-on-a-chip”-associated research with an example of double-channel chip. ЛА — pulmonary artery; ЛВ — pulmonary vein; ГВ — smooth-muscle fibers; АМе — alveolar sac; ЛК — pulmonary capillaries; АI — typeI alveolocyte; AII — type II alveolocyte; АМ — alveolar macrophage; Э — endotheliocytes; FLIM — Fluorescent Lifetime Imaging Microscopy; FRET — Förster Resonance Energy Transfer.

Download (1MB)
Indexing metadata

Copyright (c) 2024 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».