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Recent advances in lung-on-a-chip technology for modeling respiratory disease

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Abstract

Tissue engineering approaches, including those to functional lung tissues, are finely honed by the inclusion of upgraded devices that mimic biophysical and biochemical features in vivo. Perfusion culture is one of these essential biophysical characteristics enabled by the introduction of microfluidic devices in recent years. This review links the importance of dynamic culture for in vitro maintenance of functional lung cells to the modeling of respiratory disease. We identify and discuss different parameters for fabricating the requisite microfluidic models for lung cells, as well as their application in modeling lung diseases caused by external factors such as smoking and pollution. The possibility of creating a multi-organ-on-a-chip to establish a more physiologically relevant model is highlighted. Overall, the focus is on different prospects for the in vitro modeling approach and for lungs-on-a-chip for developing advanced, reliable technology to analyze the pathophysiology of respiratory diseases and screen potential treatments.

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References

  1. Levine SM, Marciniuk DD (2022) Global impact of respiratory diseases: what can we do, together, to make a difference? Chest 161(5):1153–1154. https://doi.org/10.1016/j.chest.2022.01.014

    Article  Google Scholar 

  2. Cotes JE, Chinn DJ, Miller MR (2006) Lung Function: Physiology, Measurement and Application in Medicine (6th Ed.). Blackwell Pub, Malden

    Book  Google Scholar 

  3. Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660

    Article  Google Scholar 

  4. Artzy-Schnirman A, Hobi N, Schneider-Daum N et al (2019) Advanced in vitro lung-on-chip platforms for inhalation assays: from prospect to pipeline. Eur J Pharm Biopharm 144:11–17. https://doi.org/10.1016/j.ejpb.2019.09.006

    Article  Google Scholar 

  5. Cron RQ, Caricchio R, Chatham WW (2021) Calming the cytokine storm in COVID-19. Nat Med 27(10):1674–1675. https://doi.org/10.1038/s41591-021-01500-9

    Article  Google Scholar 

  6. Ho JQ, Sepand MR, Bigdelou B et al (2022) The immune response to COVID-19: does sex matter? Immunology 166(4):429–443. https://doi.org/10.1111/imm.13487

    Article  Google Scholar 

  7. Van Norman GA (2019) Limitations of animal studies for predicting toxicity in clinical trials: is it time to rethink our current approach? JACC Basic Transl Sci 4(7):845–854. https://doi.org/10.1016/j.jacbts.2019.10.008

    Article  Google Scholar 

  8. Bhowmick R, Derakhshan T, Liang Y et al (2018) A three-dimensional human tissue-engineered lung model to study influenza A infection. Tissue Eng Part A 24(19–20):1468–1480. https://doi.org/10.1089/ten.TEA.2017.0449

    Article  Google Scholar 

  9. Mazrouei R, Velasco V, Esfandyarpour R (2020) 3D-bioprinted all-inclusive bioanalytical platforms for cell studies. Sci Rep 10:14669. https://doi.org/10.1038/s41598-020-71452-6

    Article  Google Scholar 

  10. Velasco V, Shariati SA, Esfandyarpour R (2020) Microtechnology-based methods for organoid models. Microsyst Nanoeng 6:76. https://doi.org/10.1038/s41378-020-00185-3

    Article  Google Scholar 

  11. Shrestha J, Razavi Bazaz S, Aboulkheyr Es H et al (2020) Lung-on-a-chip: the future of respiratory disease models and pharmacological studies. Crit Rev Biotechnol 40(2):213–230. https://doi.org/10.1080/07388551.2019.1710458

    Article  Google Scholar 

  12. Birgersdotter A, Sandberg R, Ernberg I (2005) Gene expression perturbation in vitro—a growing case for three-dimensional (3D) culture systems. Semin Cancer Biol 15(5):405–412. https://doi.org/10.1016/j.semcancer.2005.06.009

    Article  Google Scholar 

  13. Velasco V, Joshi K, Chen J et al (2019) Personalized drug efficacy monitoring chip. Anal Chem 91(23):14927–14935. https://doi.org/10.1021/acs.analchem.9b03291

    Article  Google Scholar 

  14. Esfandyarpour R, Esfandyarpour H, Harris JS et al (2013) Simulation and fabrication of a new novel 3D injectable biosensor for high throughput genomics and proteomics in a lab-on-a-chip device. Nanotechnology 24(46):465301. https://doi.org/10.1088/0957-4484/24/46/465301

    Article  Google Scholar 

  15. Esfandyarpour R, Esfandyarpour H, Javanmard M et al (2012) Electrical detection of protein biomarkers using nanoneedle biosensors. MRS Online Proc Libr 1414(1):7–14. https://doi.org/10.1557/opl.2012.807

    Article  Google Scholar 

  16. Esfandyarpour R, Esfandyarpour H, Javanmard M et al (2013) Microneedle biosensor: a method for direct label-free real time protein detection. Sens Actuat B Chem 177:848–855. https://doi.org/10.1016/j.snb.2012.11.064

    Article  Google Scholar 

  17. Esfandyarpour R, Javanmard M, Harris J et al (2014) Label-free electronic detection of target cells. Proc SPIE 1:8976. https://doi.org/10.1117/12.2037966

    Article  Google Scholar 

  18. Kumar S, Esfandyarpour R, Davis R et al (2014) Surface charge sensing by altering the phase transition in VO2. J Appl Phys 116(7):074511. https://doi.org/10.1063/1.4893577

    Article  Google Scholar 

  19. Esfandyarpour R, DiDonato MJ, Yang Y et al (2017) Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis. Proc Natl Acad Sci USA 114(8):E1306–E1315. https://doi.org/10.1073/pnas.1621318114

    Article  Google Scholar 

  20. Esfandyarpour R, Koochak Z, Harris JS et al (2015) Rapid, label free, high throughput, miniaturized, and inexpensive nanoelectronic array as a cancer diagnosis tool. In: 18th International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers), pp. 1523–1526

  21. Esfandyarpour R, Yang L, Koochak Z et al (2016) Nanoelectronic three-dimensional (3D) nanotip sensing array for real-time, sensitive, label-free sequence specific detection of nucleic acids. Biomed Microdevices 18(1):7. https://doi.org/10.1007/s10544-016-0032-8

    Article  Google Scholar 

  22. Joshi K, Esfandyarpour R (2020) An inkjet-printed and reusable platform for single cell impedance cytometry. Microfluidics Biomems Med Microsyst 18:11235. https://doi.org/10.1117/12.2543160

    Article  Google Scholar 

  23. Joshi K, Javani A, Park J et al (2020) A machine learning-assisted nanoparticle-printed biochip for real-time single cancer cell analysis. Adv Biosyst 4(11):2000160. https://doi.org/10.1002/adbi.202000160

    Article  Google Scholar 

  24. Joshi K, Velasco V, Esfandyarpour R (2020) A low-cost, disposable and portable inkjet-printed biochip for the developing world. Sensors 20(12):3593. https://doi.org/10.3390/s20123593

    Article  Google Scholar 

  25. Elbert KJ, Schafer UF, Schafers HJ et al (1999) Monolayers of human alveolar epithelial cells in primary culture for pulmonary absorption and transport studies. Pharm Res 16(5):601–608. https://doi.org/10.1023/a:1018887501927

    Article  Google Scholar 

  26. Sucre JMS, Jetter CS, Loomans H et al (2018) Successful establishment of primary type II alveolar epithelium with 3D organotypic coculture. Am J Respir Cell Mol Biol 59(2):158–166. https://doi.org/10.1165/rcmb.2017-0442MA

    Article  Google Scholar 

  27. Evans KV, Lee JH (2020) Alveolar wars: the rise of in vitro models to understand human lung alveolar maintenance, regeneration, and disease. Stem Cells Transl Med 9(8):867–881. https://doi.org/10.1002/sctm.19-0433

    Article  Google Scholar 

  28. Jiang D, Schaefer N, Chu HW (2018) Air–liquid interface culture of human and mouse airway epithelial cells. Methods Mol Biol 1809:91–109. https://doi.org/10.1007/978-1-4939-8570-8_8

    Article  Google Scholar 

  29. Bluhmki T, Bitzer S, Gindele JA et al (2020) Development of a miniaturized 96-transwell air-liquid interface human small airway epithelial model. Sci Rep 10:13022. https://doi.org/10.1038/s41598-020-69948-2

    Article  Google Scholar 

  30. Xu W, Janocha AJ, Leahy RA et al (2014) A novel method for pulmonary research: assessment of bioenergetic function at the air–liquid interface. Redox Biol 2:513–519. https://doi.org/10.1016/j.redox.2014.01.004

    Article  Google Scholar 

  31. Fang Y, Eglen RM (2017) Three-dimensional cell cultures in drug discovery and development. SLAS Discov 22(5):456–472. https://doi.org/10.1177/1087057117696795

    Article  Google Scholar 

  32. Hofer M, Lutolf MP (2021) Engineering organoids. Nat Rev Mater 6(5):402–420. https://doi.org/10.1038/s41578-021-00279-y

    Article  Google Scholar 

  33. Kim J, Koo BK, Knoblich JA (2020) Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol 21(10):571–584. https://doi.org/10.1038/s41580-020-0259-3

    Article  Google Scholar 

  34. Cores J, Dinh PC, Hensley T et al (2020) A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis. Stem Cells Transl Med 9(7):786–798. https://doi.org/10.1002/sctm.19-0167

    Article  Google Scholar 

  35. Dinh PC, Cores J, Hensley MT et al (2017) Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies. Respir Res 18:132. https://doi.org/10.1186/s12931-017-0611-0

    Article  Google Scholar 

  36. Li Z, Qian Y, Li W et al (2020) Human lung adenocarcinoma-derived organoid models for drug screening. iScience 23(8):1011. https://doi.org/10.1016/j.isci.2020.101411

    Article  Google Scholar 

  37. Mehta G, Hsiao AY, Ingram M et al (2012) Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J Contr Release 164(2):192–204. https://doi.org/10.1016/j.jconrel.2012.04.045

    Article  Google Scholar 

  38. Crabbé A, Liu Y, Sarker SF et al (2015) Recellularization of decellularized lung scaffolds is enhanced by dynamic suspension culture. PLoS ONE 10(5):e0126846. https://doi.org/10.1371/journal.pone.0126846

  39. Allen AB, Priddy LB, Li MT et al (2015) Functional augmentation of naturally-derived materials for tissue regeneration. Ann Biomed Eng 43(3):555–567. https://doi.org/10.1007/s10439-014-1192-4

    Article  Google Scholar 

  40. Rezaei FS, Khorshidian A, Beram FM et al (2021) 3D printed chitosan/polycaprolactone scaffold for lung tissue engineering: hope to be useful for COVID-19 studies. RSC Adv 11(32):19508–19520. https://doi.org/10.1039/d1ra03410c

    Article  Google Scholar 

  41. Wang X, Zhang X, Dai X et al (2018) Tumor-like lung cancer model based on 3D bioprinting. 3 Biotech 8(12):501. https://doi.org/10.1007/s13205-018-1519-1

  42. Young BM, Shankar K, Allen BP et al (2017) Electrospun decellularized lung matrix scaffold for airway smooth muscle culture. ACS Biomater Sci Eng 3(12):3480–3492. https://doi.org/10.1021/acsbiomaterials.7b00384

    Article  Google Scholar 

  43. Wan X, Ball S, Willenbrock F et al (2017) Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation. Sci Rep 7:9408. https://doi.org/10.1038/s41598-017-09686-0

    Article  Google Scholar 

  44. Halldorsson S, Lucumi E, Gomez-Sjoberg R et al (2015) Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices. Biosens Bioelectron 63:218–231. https://doi.org/10.1016/j.bios.2014.07.029

    Article  Google Scholar 

  45. Kim T, Yi Q, Hoang E et al (2021) A 3D printed wearable bioelectronic patch for multi-sensing and in situ sweat electrolyte monitoring. Adv Mater Technol 6(4):2001021. https://doi.org/10.1002/admt.202001021

    Article  Google Scholar 

  46. Ruzycka M, Cimpan MR, Rios-Mondragon I et al (2019) Microfluidics for studying metastatic patterns of lung cancer. J Nanobiotechnol 17:71. https://doi.org/10.1186/s12951-019-0492-0

    Article  Google Scholar 

  47. Zhang M, Xu C, Jiang L et al (2018) A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol Res 7(6):1048–1060. https://doi.org/10.1039/c8tx00156a

    Article  Google Scholar 

  48. Huh D, Matthews BD, Mammoto A et al (2010) Reconstituting organ-level lung functions on a chip. Science 328(5986):1662–1668. https://doi.org/10.1126/science.1188302

    Article  Google Scholar 

  49. Huh DD (2015) A human breathing lung-on-a-chip. Ann Am Thorac Soc 12(Suppl 1):S42–S44. https://doi.org/10.1513/AnnalsATS.201410-442MG

    Article  MathSciNet  Google Scholar 

  50. Stucki AO, Stucki JD, Hall SR et al (2015) A lung-on-a-chip array with an integrated bio-inspired respiration mechanism. Lab Chip 15(5):1302–1310. https://doi.org/10.1039/c4lc01252f

    Article  Google Scholar 

  51. Zamprogno P, Wuthrich S, Achenbach S et al (2021) Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane. Commun Biol 4:168. https://doi.org/10.1038/s42003-021-01695-0

    Article  Google Scholar 

  52. Ochs M, Nyengaard JR, Jung A et al (2004) The number of alveoli in the human lung. Am J Respir Crit Care Med 169(1):120–124. https://doi.org/10.1164/rccm.200308-1107OC

    Article  Google Scholar 

  53. Huang D, Liu T, Liao J et al (2021) Reversed-engineered human alveolar lung-on-a-chip model. Proc Natl Acad Sci USA 118(19):e2016146118. https://doi.org/10.1073/pnas.2016146118

    Article  Google Scholar 

  54. Aleman J, Kilic T, Mille LS et al (2021) Microfluidic integration of regeneratable electrochemical affinity-based biosensors for continual monitoring of organ-on-a-chip devices. Nat Protoc 16(5):2564–2593. https://doi.org/10.1038/s41596-021-00511-7

    Article  Google Scholar 

  55. Srinivasan B, Kolli AR, Esch MB et al (2015) TEER measurement techniques for in vitro barrier model systems. J Lab Autom 20(2):107–126. https://doi.org/10.1177/2211068214561025

    Article  Google Scholar 

  56. Bovard D, Giralt A, Trivedi K et al (2020) Comparison of the basic morphology and function of 3D lung epithelial cultures derived from several donors. Curr Res Toxicol 1:56–69. https://doi.org/10.1016/j.crtox.2020.08.002

    Article  Google Scholar 

  57. Henry OYF, Villenave R, Cronce MJ et al (2017) Organs-on-chips with integrated electrodes for trans-epithelial electrical resistance (TEER) measurements of human epithelial barrier function. Lab Chip 17(13):2264–2271. https://doi.org/10.1039/c7lc00155j

    Article  Google Scholar 

  58. Molloy K, Cagney G, Dillon ET et al (2020) Impaired airway epithelial barrier integrity in response to stenotrophomonas maltophilia proteases, novel insights using cystic fibrosis bronchial epithelial cell secretomics. Front Immunol 11:198. https://doi.org/10.3389/fimmu.2020.00198

    Article  Google Scholar 

  59. Doryab A, Taskin MB, Stahlhut P et al (2021) A bioinspired in vitro lung model to study particokinetics of nano-/microparticles under cyclic stretch and air-liquid interface conditions. Front Bioeng Biotechnol 9:616830. https://doi.org/10.3389/fbioe.2021.616830

    Article  Google Scholar 

  60. Mermoud Y, Felder M, Stucki JD et al (2018) Microimpedance tomography system to monitor cell activity and membrane movements in a breathing lung-on-chip. Sensor Actuat B Chem 255:3647–3653. https://doi.org/10.1016/j.snb.2017.09.192

    Article  Google Scholar 

  61. Skardal A, Murphy SV, Devarasetty M et al (2017) Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep 7:8837. https://doi.org/10.1038/s41598-017-08879-x

    Article  Google Scholar 

  62. Zhang F, Liu WM, Zhou SS et al (2020) Investigation of environmental pollutant-induced lung inflammation and injury in a 3D coculture-based microfluidic pulmonary alveolus system. Anal Chem 92(10):7200–7208. https://doi.org/10.1021/acs.analchem.0c00759

    Article  Google Scholar 

  63. Mejías JC, Nelson MR, Liseth O et al (2020) A 96-well format microvascularized human lung-on-a-chip platform for microphysiological modeling of fibrotic diseases. Lab Chip 20(19):3601–3611. https://doi.org/10.1039/d0lc00644k

    Article  Google Scholar 

  64. Lee SW, Kwak HS, Kang MH et al (2018) Fibroblast-associated tumour microenvironment induces vascular structure-networked tumouroid. Sci Rep 8:2365. https://doi.org/10.1038/s41598-018-20886-0

    Article  Google Scholar 

  65. Das P, Najafikhoshnoo S, Tavares-Negrete JA et al (2022) An in-vivo-mimicking 3D lung cancer-on-a-chip model to study the effect of external stimulus on the progress and inhibition of cancer metastasis. Bioprinting 28:e00243 https://doi.org/10.1016/j.bprint.2022.e00243

  66. Khalid MAU, Kim YS, Ali M et al (2020) A lung cancer-on-chip platform with integrated biosensors for physiological monitoring and toxicity assessment. Biochem Eng J 155:107469. https://doi.org/10.1016/j.bej.2019.107469

    Article  Google Scholar 

  67. Al-Hilal TA, Keshavarz A, Kadry H et al (2020) Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application. Lab Chip 20(18):3334–3345. https://doi.org/10.1039/d0lc00605j

    Article  Google Scholar 

  68. Schimek K, Frentzel S, Luettich K et al (2020) Human multi-organ chip co-culture of bronchial lung culture and liver spheroids for substance exposure studies. Sci Rep 10:7865. https://doi.org/10.1038/s41598-020-64219-6

    Article  Google Scholar 

  69. Kim D, Chen Z, Zhou LF et al (2018) Air pollutants and early origins of respiratory diseases. Chronic Dis Transl Med 4(2):75–94. https://doi.org/10.1016/j.cdtm.2018.03.003

    Article  Google Scholar 

  70. Reza Sepand M, Bigdelou B, Salek Maghsoudi A et al (2023) Ferroptosis: Environmental causes, biological redox signaling responses, cancer and other health consequences. Coord Chem Rev 480:215024. https://doi.org/10.1016/j.ccr.2023.215024

    Article  Google Scholar 

  71. Zhang F, Tian C, Liu W et al (2018) Determination of benzopyrene-induced lung inflammatory and cytotoxic injury in a chemical gradient-integrated microfluidic bronchial epithelium system. ACS Sens 3(12):2716–2725. https://doi.org/10.1021/acssensors.8b01370

    Article  Google Scholar 

  72. Xu C, Zhang M, Chen W et al (2020) Assessment of air pollutant PM2.5 pulmonary exposure using a 3D lung-on-chip model. ACS Biomater Sci Eng 6(5):3081–3090. https://doi.org/10.1021/acsbiomaterials.0c00221

    Article  Google Scholar 

  73. Plebani R, Potla R, Soong M et al (2022) Modeling pulmonary cystic fibrosis in a human lung airway-on-a-chip. J Cyst Fibros 21(4):606–615. https://doi.org/10.1016/j.jcf.2021.10.004

    Article  Google Scholar 

  74. Islami F, Goding Sauer A, Miller KD et al (2018) Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin 68(1):31–54. https://doi.org/10.3322/caac.21440

    Article  Google Scholar 

  75. Shrestha J, Ghadiri M, Shanmugavel M et al (2019) A rapidly prototyped lung-on-a-chip model using 3D-printed molds. Organs-on-a-Chip 1:100001. https://doi.org/10.1016/j.ooc.2020.100001

    Article  Google Scholar 

  76. Jones B, Donovan C, Liu G et al (2017) Animal models of COPD: what do they tell us? Respirology 22(1):21–32. https://doi.org/10.1111/resp.12908

    Article  Google Scholar 

  77. Hou W, Hu SY, Yong KT et al (2020) Cigarette smoke-induced malignant transformation via STAT3 signalling in pulmonary epithelial cells in a lung-on-a-chip model. Bio-Des Manuf 3(4):383–395. https://doi.org/10.1007/s42242-020-00092-6

    Article  Google Scholar 

  78. Benam KH, Novak R, Ferrante TC et al (2020) Biomimetic smoking robot for in vitro inhalation exposure compatible with microfluidic organ chips. Nat Protoc 15(2):183–206. https://doi.org/10.1038/s41596-019-0230-y

    Article  Google Scholar 

  79. Benam KH, Mazur M, Choe Y et al (2017) Human lung small airway-on-a-chip protocol. Methods Mol Biol 1612:345–365. https://doi.org/10.1007/978-1-4939-7021-6_25

    Article  Google Scholar 

  80. Cetintas E, Luo Y, Nguyen C et al (2022) Characterization of exhaled e-cigarette aerosols in a vape shop using a field-portable holographic on-chip microscope. Sci Rep 12:3175. https://doi.org/10.1038/s41598-022-07150-2

    Article  Google Scholar 

  81. Reyfman PA, Walter JM, Joshi N et al (2019) Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am J Respir Crit Care Med 199(12):1517–1536. https://doi.org/10.1164/rccm.201712-2410OC

    Article  Google Scholar 

  82. Ratjen F, Bell SC, Rowe SM et al (2015) Cystic fibrosis. Nat Rev Dis Primers 1:15010. https://doi.org/10.1038/nrdp.2015.10

    Article  Google Scholar 

  83. Park S, Kim TH, Kim SH et al (2021) Three-dimensional vascularized lung cancer-on-a-chip with lung extracellular matrix hydrogels for in vitro screening. Cancers 13(16):3930. https://doi.org/10.3390/cancers13163930

    Article  Google Scholar 

  84. Xu Z, Li E, Guo Z et al (2016) Design and construction of a multi-organ microfluidic chip mimicking the in vivo microenvironment of lung cancer metastasis. ACS Appl Mater Interfaces 8(39):25840–25847. https://doi.org/10.1021/acsami.6b08746

    Article  Google Scholar 

  85. Esfandyarpour R (2013) Electrical Response of DNA and Proteins at Nanoscale by Using Novel Nanoneedle Biosensor. Nanotech

  86. Esfandyarpour R, Javanmard M, Koochak Z et al (2013) Thin film nanoelectronic probe for protein detection. MRS Online Proc Libr 1572:110. https://doi.org/10.1557/opl.2013.660

    Article  Google Scholar 

  87. Esfandyarpour R, Javanmard M, Koochak Z et al (2013) Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor. Biomicrofluidics 1508 7(4):044114. https://doi.org/10.1063/1.4817771

  88. Esfandyarpour R, Javanmard M, Koochak Z et al (2014) Matrix Independent Label-Free Nanoelectronic Biosensor. In: IEEE 27th International Conference on Micro Electro Mechanical Systems, pp. 1083–1086

  89. Esfandyarpour R, Javanmard M, Koochak Z et al (2014) Nanoelectronic impedance detection of target cells. Biotechnol Bioeng 111(6):1161–1169. https://doi.org/10.1002/bit.25171

    Article  Google Scholar 

  90. Esfandyarpour R, Kashi A, Nemat-Gorgani M et al (2019) A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Proc Natl Acad Sci USA 116(21):10250–10257. https://doi.org/10.1073/pnas.1901274116

    Article  Google Scholar 

  91. NajafiKhoshnoo S, Kim T, Tavares-Negrete JA et al (2023) A 3D nanomaterials-printed wearable, battery-free, biocompatible, flexible, and wireless pH sensor system for real-time health monitoring. Adv Mater Technol 8(8):2201655 https://doi.org/10.1002/admt.202201655

  92. Yi Q, Najafikhoshnoo S, Das P et al (2022) All-3D-printed, flexible, and hybrid wearable bioelectronic tactile sensors using biocompatible nanocomposites for health monitoring. Adv Mater Technol 7(5):2101034. https://doi.org/10.1002/admt.202101034

  93. Yi Q, Pei XC, Das P et al (2022) A self-powered triboelectric MXene-based 3D-printed wearable physiological biosignal sensing system for on-demand, wireless, and real-time health monitoring. Nano Energy 101:107511. https://doi.org/10.1016/j.nanoen.2022.107511

    Article  Google Scholar 

  94. Pollet A, den Toonder JMJ (2020) Recapitulating the vasculature using organ-on-chip technology. Bioengineering 7(1):17. https://doi.org/10.3390/bioengineering7010017

    Article  Google Scholar 

  95. Trujillo-de Santiago G, Flores-Garza BG, Tavares-Negrete JA et al (2019) The tumor-on-chip: recent advances in the development of microfluidic systems to recapitulate the physiology of solid tumors. Materials 12(18):2945. https://doi.org/10.3390/ma12182945

    Article  Google Scholar 

  96. Dharmage SC, Perret JL, Custovic A (2019) Epidemiology of asthma in children and adults. Front Pediatr 7:246. https://doi.org/10.3389/fped.2019.00246

    Article  Google Scholar 

  97. Pavord ID, Beasley R, Agusti A et al (2018) After asthma: redefining airways diseases. Lancet 391(10118):350–400. https://doi.org/10.1016/S0140-6736(17)30879-6

    Article  Google Scholar 

  98. Abrams EM, Jong GW, Yang CL (2020) Asthma and COVID-19. CMAJ 192(20):E551. https://doi.org/10.1503/cmaj.200617

    Article  Google Scholar 

  99. Nawroth JC, Lucchesi C, Cheng D et al (2020) A Microengineered airway lung chip models key features of viral-induced exacerbation of asthma. Am J Respir Cell Mol Biol 63(5):591–600. https://doi.org/10.1165/rcmb.2020-0010MA

    Article  Google Scholar 

  100. Fan EKY, Fan J (2018) Regulation of alveolar macrophage death in acute lung inflammation. Respir Res 19:50. https://doi.org/10.1186/s12931-018-0756-5

    Article  Google Scholar 

  101. Benam KH, Villenave R, Lucchesi C et al (2016) Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods 13(2):151–157. https://doi.org/10.1038/nmeth.3697

    Article  Google Scholar 

  102. Punde TH, Wu WH, Lien PC et al (2015) A biologically inspired lung-on-a-chip device for the study of protein-induced lung inflammation. Integr Biol 7(2):162–169. https://doi.org/10.1039/c4ib00239c

    Article  Google Scholar 

  103. Chin KM, Rubin LJ (2008) Pulmonary arterial hypertension. J Am Coll Cardiol 51(16):1527–1538. https://doi.org/10.1016/j.jacc.2008.01.024

    Article  Google Scholar 

  104. Tas S, Rehnberg E, Bölükbas DA et al (2021) 3D printed lung on a chip device with a stretchable nanofibrous membrane for modeling ventilator induced lung injury. bioRxiv:2021.2007.2002.450873 https://doi.org/10.1101/2021.07.02.450873

  105. Jain A, Barrile R, van der Meer AD et al (2018) Primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics. Clin Pharmacol Ther 103(2):332–340. https://doi.org/10.1002/cpt.742

    Article  Google Scholar 

  106. Felder M, Trueeb B, Stucki AO et al (2019) Impaired wound healing of alveolar lung epithelial cells in a breathing lung-on-a-chip. Front Bioeng Biotechnol 7:3. https://doi.org/10.3389/fbioe.2019.00003

    Article  Google Scholar 

  107. Pinhu L, Whitehead T, Evans T et al (2003) Ventilator-associated lung injury. Lancet 361(9354):332–340. https://doi.org/10.1016/S0140-6736(03)12329-X

    Article  Google Scholar 

  108. Rehnberg E, Tas S, Bölükbas DA et al (2021) Lung-on-a-chip device for modelling of ventilator induced lung injury. ERJ Open Research 7:1

    Google Scholar 

  109. Amoretti M, Amsler C, Bonomi G et al (2002) Production and detection of cold antihydrogen atoms. Nature 419(6906):456–459. https://doi.org/10.1038/nature01096

    Article  Google Scholar 

  110. Vanegas MI, Hubbard KR, Esfandyarpour R et al (2019) Microinjectrode system for combined drug infusion and electrophysiology. Jove J Vis Exp 2019(153):e60365. https://doi.org/10.3791/60365

    Article  Google Scholar 

  111. Mani V, Lyu Z, Kumar V et al (2019) Epithelial-to-mesenchymal transition (EMT) and drug response in dynamic bioengineered lung cancer microenvironment. Adv Biosyst 3(1):e1800223 https://doi.org/10.1002/adbi.201800223

  112. Meghani N, Kim KH, Kim SH et al (2020) Evaluation and live monitoring of pH-responsive HSA-ZnO nanoparticles using a lung-on-a-chip model. Arch Pharm Res 43(5):503–513. https://doi.org/10.1007/s12272-020-01236-z

    Article  Google Scholar 

  113. Xu Z, Gao Y, Hao Y et al (2013) Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials 34(16):4109–4117. https://doi.org/10.1016/j.biomaterials.2013.02.045

    Article  Google Scholar 

  114. Yang X, Li K, Zhang X et al (2018) Nanofiber membrane supported lung-on-a-chip microdevice for anti-cancer drug testing. Lab Chip 18(3):486–495. https://doi.org/10.1039/c7lc01224a

    Article  Google Scholar 

  115. George PM, Wells AU, Jenkins RG (2020) Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med 8(8):807–815. https://doi.org/10.1016/S2213-2600(20)30225-3

    Article  Google Scholar 

  116. Ojo AS, Balogun SA, Williams OT et al (2020) Pulmonary fibrosis in COVID-19 survivors: predictive factors and risk reduction strategies. Pulm Med 2020:6175964. https://doi.org/10.1155/2020/6175964

    Article  Google Scholar 

  117. Mason RJ (2020) Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J 55(4):2000607. https://doi.org/10.1183/13993003.00607-2020

    Article  Google Scholar 

  118. Bigdelou B, Sepand MR, Najafikhoshnoo S et al (2022) COVID-19 and preexisting comorbidities: risks, synergies, and clinical outcomes. Front Immunol 13:890517. https://doi.org/10.3389/fimmu.2022.890517

    Article  Google Scholar 

  119. Nicholson LB (2016) The immune system. Essays Biochem 60(3):275–301. https://doi.org/10.1042/EBC20160017

    Article  Google Scholar 

  120. Zhang M, Wang P, Luo R et al (2021) Biomimetic human disease model of SARS-CoV-2-induced lung injury and immune responses on organ chip system. Adv Sci 8(3):2002928. https://doi.org/10.1002/advs.202002928

    Article  Google Scholar 

  121. Si L, Bai H, Rodas M et al (2021) A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat Biomed Eng 5(8):815–829. https://doi.org/10.1038/s41551-021-00718-9

    Article  Google Scholar 

  122. Long C, Finch C, Esch M et al (2012) Design optimization of liquid-phase flow patterns for microfabricated lung on a chip. Ann Biomed Eng 40(6):1255–1267. https://doi.org/10.1007/s10439-012-0513-8

    Article  Google Scholar 

  123. Sengupta A, Roldan N, Kiener M et al (2022) A new immortalized human alveolar epithelial cell model to study lung injury and toxicity on a breathing lung-on-chip system. Front Toxicol 4:840606. https://doi.org/10.3389/ftox.2022.840606

    Article  Google Scholar 

  124. Konar D, Devarasetty M, Yildiz DV et al (2016) Lung-on-a-chip technologies for disease modeling and drug development. Biomed Eng Comput Biol 7(Suppl 1):17–27. https://doi.org/10.4137/BECB.S34252

    Article  Google Scholar 

  125. Alberts B (2002) Molecular Biology of the Cell (4th Ed.). Garland Science, New York

    Google Scholar 

  126. Toepke MW, Beebe DJ (2006) PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip 6(12):1484–1486. https://doi.org/10.1039/b612140c

    Article  Google Scholar 

  127. Campbell SB, Wu Q, Yazbeck J et al (2021) Beyond polydimethylsiloxane: alternative materials for fabrication of organ-on-a-chip devices and microphysiological systems. ACS Biomater Sci Eng 7(7):2880–2899. https://doi.org/10.1021/acsbiomaterials.0c00640

    Article  Google Scholar 

  128. Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5(4):263–274. https://doi.org/10.1038/nrc1586

    Article  Google Scholar 

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Acknowledgements

We gratefully thank the startup funding of R.E. by the Henry Samueli School of Engineering and the Department of Electrical Engineering at the University of California, Irvine. J.A.T-N. acknowledges the Consejo Nacional de Ciencia y Tecnología (CONACyT, Mexico) and the University of California for the support provided under the UC MEXUS-CONACYT doctoral fellowships.

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Author notes

  1. Jorge A. Tavares-Negrete and Prativa Das have contributed equally to this work.

Authors and Affiliations

  1. Department of Electrical Engineering, University of California, Irvine, CA, 92697, USA

    Prativa Das, Sahar Najafikhoshnoo & Rahim Esfandyarpour

  2. Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA

    Jorge A. Tavares-Negrete & Rahim Esfandyarpour

  3. Henry Samueli School of Engineering, University of California, Irvine, CA, 92697, USA

    Rahim Esfandyarpour

  4. Laboratory for Integrated Nano Bio Electronics Innovation, Henry Samueli School of Engineering, University of California, Irvine, CA, 92697, USA

    Jorge A. Tavares-Negrete, Prativa Das, Sahar Najafikhoshnoo & Rahim Esfandyarpour

  5. Department of Mechanical and Aerospace Engineering, University of California, Irvine, CA, 92697, USA

    Rahim Esfandyarpour

  6. Department of Bioengineering, University of Massachusetts Dartmouth, Dartmouth, MA, USA

    Steven Zanganeh

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  1. Jorge A. Tavares-Negrete
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Contributions

RE conceptualized the paper. JATN, PD, SN, and RE collected the data and wrote the original draft. JATN, PD, SN, SZ, and RE reviewed and edited the document. All authors provided feedback.

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Correspondence to Rahim Esfandyarpour.

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Tavares-Negrete, J.A., Das, P., Najafikhoshnoo, S. et al. Recent advances in lung-on-a-chip technology for modeling respiratory disease. Bio-des. Manuf. 6, 563–585 (2023). https://doi.org/10.1007/s42242-023-00241-7

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