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Reconstituting Organ-Level Lung Functions on a Chip
Open accessAbstract
Just Breathe: Design of artificial systems that mimic in vivo organs could provide a better alternative for understanding mechanisms underlying physiological responses than current cell-based models or animal tests. Huh et al. (p. 1662 ) have created a tissue-tissue interface of human-cultured epithelial cells and endothelial cells together, with extracellular matrix in a device that models the alveolar-capillary interface of the human lung. The device mimicked physiological organ-level functions, including pathogen-induced inflammatory responses and responses to cytokine exposure. Breathing-type movements affected acute pulmonary cell toxicity and proinflammatory activity of widely used nanoparticulates.
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“most models rely on the integration of only a few, pre-defined immune cell types, which, however, does not emulate the complexity of in vivo immunoregulation”
From Human disease models in drug development (2023) · cites this paper as [143]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Biomechanical stimuli, such as shear stress, stretching or compression, influence (patho)physiological processes142–147”
From Human disease models in drug development (2023) · cites this paper as [143]
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In the citing paper
“Regarding the chip’s main structure, the traditional choice is poly(dimethylsiloxane) (PDMS) (Huh et al., 2010), a silicone rubber that is easily fabricated using lithographic design templates. This choice provides flexibility in the design, oxygen permeability, optical transparency, and biocompatibility.”
From Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility (2024) · cites this paper as Huh et al., 2010
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“This problem can be partially resolved using shaking cultures23 93, spinning bioreactors or suspension under continuous agitation23, or in continuously stirred bioreactors93.”
From Organoids (2022) · cites this paper as [93]
Experimental — accuracy not yet measuredIn the citing paper
“Earlier, Huh et al.131 used a bionic microsystem to reconstruct the alveolar–capillary interface of the key function of the human lung. This model can produce a complex, integrated organ-level response to bacteria and inflammatory cytokines entering the alveolar space.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [131]
In the citing paper
“Unlike simple two-dimensional cell cultures, the development of biomimetic organ-on-a-chip and tissue-on-a-chip systems may enable researchers to more accurately predict the behaviour of nanomedicines in a controlled setting by considering cell-cell interactions, interstitial flow and nanoparticle transport in three dimensions93,94.”
From How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (2018) · cites this paper as [93]
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Metadata
- Authors
- Huh, D., Matthews, B. D., Mammoto, A., Montoya-Zavala, M., Hsin, H. Y., & Ingber, D. E.
- Affiliations
- Boston Children's Hospital (US)
- Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
- Corresponding author
- Ingber, Donald E.
- Venue
- Science
- Published
- 2010-06-25
- Volume
- 328
- Issue
- 5986
- Pages
- 1662-1668
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8335790
- OpenAlex
- W2076922024
- Cited by
- 4,250
- References
- 41
- Citations by year
- 2026: 337 · 2025: 311 · 2024: 372 · 2023: 369 · 2022: 367 · 2021: 371 · 2020: 300 · 2019: 302 · 2018: 286 · 2017: 288 · 2016: 220 · 2015: 166 · 2014: 188 · 2013: 156 · 2012: 110
- FWCI
- 68.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (R01ES016665)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- organ-on-a-chip, lung-on-a-chip, cyclic strain, silica nanoparticles, nanoparticle uptake, nanoparticle transport, inflammation, bacterial infection, inhalation exposure, alternatives to animal testing, drug screening, toxicology
- MeSH terms
- Air, Animals, Capillaries, Capillary Permeability, Cells, Cultured, Escherichia coli, Humans, Immunity, Innate, Inflammation, Lung, Pulmonary Alveoli, Respiration, Silicon Dioxide, Stress, Mechanical, Blood-Air Barrier, Oxidative Stress, Neutrophil Infiltration, Biomimetic Materials, Endothelial Cells, Microfluidic Analytical Techniques, Mice, Nanoparticles, Microtechnology, Alveolar Epithelial Cells
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