内容简介
本综述论文聚焦用于模拟呼吸系统疾病的肺芯片技术的最新进展。随着模拟体内生物物理和生化特征的设备升级,组织工程方法(包括功能性肺组织方法)得到了完善。灌注培养是近年来随着微流控设备的引入而实现的基本生物物理特性之一。本综述将动态培养对体外维持肺细胞功能的重要性与呼吸系统疾病建模联系起来。探讨了构建肺细胞微流控模型所需的不同参数,以及它们在模拟吸烟、污染等外部因素引起的肺部疾病中的应用。强调了创建多器官芯片以建立更符合生理学的模型的可能性。综上,本文分别针对体外肺模型的构建方法和以肺器官芯片开发先进可靠的技术,从而分析呼吸系统疾病的病理生理学和筛选潜在的治疗方法,提出了其研究前景。
引用本文(点击最下方阅读原文可下载PDF)
Tavares-Negrete JA, Das P, Najafikhoshnoo S, et al., 2023. Recent advances in lung-on-a-chip technology for modeling respiratory disease. Bio-des Manuf 6(5):563-585. https://doi.org/10.1007/s42242-023-00241-7
文章导读
图1 使用芯片肺系统再现肺生理机能。(a) 细胞培养方法的演变;(b) 微流控装置的制备,以模拟肺微环境和生理;(c) 应用芯片肺系统评估与污染、吸烟、感染、纳米粒子、药物等相关的呼吸系统疾病
图2 肺研究的不同模型。(a) 动物模型;(b) 细胞单层;(c) 球体培养;(d) 生物制造中基于支架的三维培养
图3 肺芯片在疾病建模中的应用
图4 肺芯片在癌症中的应用
图5 肺芯片模拟肺部病变
图6 肺芯片与COVID-19
图7 人体肺功能的体外建模
参考文献
上下滑动以阅览
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
2. Cotes JE, Chinn DJ, Miller MR (2006) Lung Function: Physiology, Measurement and Application in Medicine (6th Ed.). Blackwell Pub, Malden
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
32. Hofer M, Lutolf MP (2021) Engineering organoids. Nat Rev Mater 6(5):402–420. https://doi.org/10.1038/s41578-021-00279-y
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
98. Abrams EM, Jong GW, Yang CL (2020) Asthma and COVID-19. CMAJ 192(20):E551. https://doi.org/10.1503/cmaj.200617
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
119. Nicholson LB (2016) The immune system. Essays Biochem 60(3):275–301. https://doi.org/10.1042/EBC20160017
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
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
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
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
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
125. Alberts B (2002) Molecular Biology of the Cell (4th Ed.). Garland Science, New York
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
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
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
关于本刊
Bio-Design and Manufacturing(中文名《生物设计与制造》),简称BDM,是浙江大学主办的专业英文双月刊,主编杨华勇院士、崔占峰院士,2018年新创,2019年已被SCI-E等库检索,2023年起改为双月刊,2023年公布的最新影响因子为7.9,位列JCR的Q1区,14/96。
初审迅速:初审快速退稿,不影响作者投其它期刊。
审稿速度快:过去两年平均录用时间约40天;平均退稿时间约10天。文章录用后及时在线SpringerLink。一般两周左右即被SCI-E检索。
收稿方向 :机械工程(3D打印及生物处理工程等)、生物墨水与配方、组织与器官工程、医学与诊断装置、生物产品设计等。
文章类型:Research Article, Review, Short Paper (包括Editorial, Perspective, Letter, Technical Note, Case Report, Lab Report, Negative Result等)。
期刊主页:
http://www.springer.com/journal/42242
http://www.jzus.zju.edu.cn/ (国内可下载全文)
在线投稿地址:
http://www.editorialmanager.com/bdmj/default.aspx
入群交流
围绕BDM刊物的投稿方向,本公众号建有“生物设计与制造”学术交流群,加小编微信号icefires212入群交流,或扫以下二维码











