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 disease models rely on the integration of only a few pre-defined immune cell types, which does not emulate the complexity of in vivo immunoregulation.
“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]
The Abstract (page not provided) says existing models fail to recreate an interface important for immune-cell transport. The Biomimetic Microsystems section (page not provided) acknowledges that this lung chip lacks alveolar macrophages. These passages support a limitation in modeling immune responses, but do not establish that most disease models integrate only a few pre-defined immune cell types. (LLM, conf=0.80)
Experimental — accuracy not yet measuredBiomechanical stimuli such as shear stress, stretching or compression influence pathophysiological processes.
“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]
The Reconstitution of a Functional Alveolar-Capillary Interface section (page unavailable) reports physiological effects of cyclic stretching, and the nanoparticle-response section reports that breathing-related strain may accentuate lung inflammation. The paper also reports a modest effect of shear stress on nanoparticle transport, but the passages do not establish an effect of compression; the claim is broader than this lung-chip evidence. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPDMS is a traditional choice for the main structure of OoC chips, providing flexibility in design, oxygen permeability, optical transparency, and biocompatibility.
“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
The fabrication passage (section labeled Abstract; page unavailable) describes PDMS layers made into microchannels by soft lithography, and another describes a flexible PDMS membrane supporting cultured cells. The paper does not establish that PDMS was the traditional choice for organ-on-chip structures or state that it provides oxygen permeability or optical transparency. (LLM, conf=0.85)
Experimental — accuracy not yet measuredShaking cultures, spinning bioreactors, suspension under continuous agitation, or continuously stirred bioreactors can partially resolve inadequate nutrient and waste diffusion in brain organoid culture.
“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]
The Abstract describes a lung-on-a-chip device, and 'Reconstitution of a Functional Alveolar-Capillary Interface' describes cyclic stretching and fluid flow; page numbers are not provided in our copy. Searches for spinning bioreactors, continuous agitation, and brain-organoid nutrient and waste diffusion found no passage addressing the attributed claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredA bionic microsystem reconstructed the alveolar-capillary interface of the key function of the human lung and can produce a complex, integrated organ-level response to bacteria and inflammatory cytokines entering the alveolar space.
“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]
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 dimensions.
“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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- 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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