ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Organoids and Organ-On-A-Chip
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1570270
This article is part of the Research TopicInsights In Organoids and Organ-On-A-Chip 2024: Novel Developments, Current Challenges and Future PerspectivesView all 9 articles
Development and application of a stepwise-assembled modular biomimetic lung chip for analyzing formaldehyde-induced cellular ferroptosis
Provisionally accepted
Siyu Chen1
Zezhi Li2Quanping Yan1Chenfeng Hua1Pingping Shang1Kejian Liu1Junwei Zhao2Guangxiang Jin3
Xiang Li2*Fuwei Xie1*- 1Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou, China
- 2Beijing Life Science Academy, Beijing, China
- 3China Tobacco Guangdong Industrial Co., LTD., Guangzhou, China
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This study developed a modular biomimetic lung chip which consists of gas concentration gradient generator module and cell culture module, assembled using alignment holes and micropillars. This design enables stepwise experimental procedures, including cell loading, gas concentration gradient exposure, and cell sample collection, through the assembly and disassembly of the modules. Using this chip to investigate the formaldehyde-induced cellular ferroptosis, BEAS-2B cells were exposed to formaldehyde under a concentration gradient. Transcriptomic sequencing revealed the effects of different formaldehyde concentrations on the expression of ferroptosis-related genes in cells, identifying 12 ferroptosis-related genes (FRGS) and an enhancement of oxidative stress. The ferroptosis inhibitor (deferoxamine mesylate) significantly reduced cell death and reactive oxygen species levels, confirming the involvement of ferroptosis in formaldehyde-induced toxicity. Furthermore, deferoxamine mesylate modulated the expression of hub genes of FRGS, including PTGS2, ATF3, CDKN1A, PLIN2, and DUOX1, at both transcript and protein levels. These findings provide novel insights into the molecular mechanisms underlying formaldehyde-induced respiratory damage and establish the modular biomimetic lung chip as a powerful platform for studying environmental toxicants.
Keywords: microfluidic, modular, stepwise-assembled, biomimetic lung chip, Formaldehyde, ferroptosis
Received: 03 Feb 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Chen, Li, Yan, Hua, Shang, Liu, Zhao, Jin, Li and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiang Li, Beijing Life Science Academy, Beijing, China
Fuwei Xie, Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou, China
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