Reconstituting Organ-Level Lung Functions on a Chip

  title={Reconstituting Organ-Level Lung Functions on a Chip},
  author={Dongeun Huh and Benjamin D. Matthews and Akiko Mammoto and Mart{\'i}n Montoya-Zavala and Hong Yuan Hsin and Donald E. Ingber},
  pages={1662 - 1668}
Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. [] Key Result This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles.

A biologically inspired lung-on-a-chip device for the study of protein-induced lung inflammation.

This study reports a biomimetic microsystem that reconstitutes the lung microenvironment for monitoring the role of eosinophil cationic protein (ECP) in lung inflammation and develops a new microfluidic model which could not only simulate the transwell for studying cell migration, but could also study the migration in the presence of a flow mimicking the physiological conditions in the body.

Biomimetic human lung-on-a-chip for modeling disease investigation.

This review summarizes current lungs-on-a-chip models based on the lung-related cellular microenvironment, including the latest advances described in studies of lung injury, inflammation, lung cancer, and pulmonary fibrosis.

Medium throughput breathing human primary cell alveolus-on-chip model

A breathing lung-on-chip array equipped with a passive medium exchange mechanism that provide an in vivo-like environment to primary human lung alveolar cells (hAEpCs) and primary lung endothelial cells, which has the potential to become a valuable tool for lung research, drug discovery and precision medicine.

Modeling a Lung-ona-Chip Microdevice

A COMSOL Multiphysics® software model of the lung-on-achip device of Huh et al. that mimics the essential features of the blood-air barrier in human and animal lungs is developed.

Biomimetic human lung alveolar interstitium chip with extended longevity

A biomimetic chip was developed to imitate key alveolar microenvironmental factors including an electrospun nanofibrous membrane as the analogue of the basement membrane for co-culture of epithelial cells with fibroblasts embedded in 3D collagenous gels and substantially improved epithelial barrier function compared to transwell models.

Microfluidic lung airway-on-a-chip with arrayable suspended gels for studying epithelial and smooth muscle cell interactions.

A thermoplastic-based microfluidic lung airway-on-a-chip model that mimics the lungAirway tissue microenvironment, and in particular, the interactions between SMC-EC-matrix interactions, and their roles in the development of CLDs is developed.

Second-generation lung-on-a-chip array with a stretchable biological membrane

A second-generation lung-on-a-chip with an array of in vivo-like sized alveoli and a stretchable biological membrane allows mimicking in vivo functionality of the lung parenchyma at an unprecedented level and makes this model a more analogous tool for drug discovery, diseases modeling and precision medicine applications.

Evolution of Bioengineered Lung Models: Recent Advances and Challenges in Tissue Mimicry for Studying the Role of Mechanical Forces in Cell Biology

It is concluded that natural‐synthetic copolymers are promising candidates for suitable stretchable membranes used in cell‐stretching models of the lung with the potential to function as a template for other organ models (e.g., skin, vessels).

Breathing on Chip: Biomechanical forces change airway epithelial cell biology in a human Airway Lung-Chip

It is suggested that breathing-associated mechanical stimulation changes epithelial composition, reduces secretion of IL-8, and downregulates gene expression of matrix metalloproteinase 9, fibronectin, and other extracellular matrix (ECM) factors.

Reversed-engineered human alveolar lung-on-a-chip model

This study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.



Primary human coculture model of alveolo-capillary unit to study mechanisms of injury to peripheral lung

The established coculture provides a suitable in vitro model to examine barrier function at the distal lung, including the interaction of microvascular endothelial cells with ATII-like and ATI-like epithelial cells.

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Towards a human-on-chip: culturing multiple cell types on a chip with compartmentalized microenvironments.

The function of A549 cells was enhanced while the functions of C3A, HK-2 and HPA cells were uncompromised, demonstrating the limited cross-talk between cell culture compartments similar to the in vivo situation.

The Design and Fabrication of Three‐Chamber Microscale Cell Culture Analog Devices with Integrated Dissolved Oxygen Sensors

The design and basic operation of the microscale manifestation of a cell culture analog system that achieves approximate physiological liquid‐to‐cell ratio and hydrodynamic shear stress while replicating the liquid residence time parameters in the PBPK model is described.

Computer-controlled microcirculatory support system for endothelial cell culture and shearing.

A self-contained microcirculatory EC culture system that efficiently studies such effects of shear stress on EC alignment and elongation in vitro by overcomes the small flow rates and the inefficiencies of previously described microfluidic and macroscopic systems respectively.

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The hypothesis is that growing endothelial cells on one side of an ultra-thin, highly porous membrane and differentiating astrocyte or astrogliomal cells on the opposite side will lead to a higher degree of interaction between the two cell types and therefore to an improved model of the blood-brain barrier.

An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture.

A biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver acinus is created.

Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity

An in vitro microscale cell culture analog (µCCA) of the GI tract that includes digestion, a mucus layer, and physiologically realistic cell populations is developed and showed that acetaminophen passes through and is metabolized by the in vitro intestinal epithelium and is further metabolizing by liver cells, resulting in liver cell toxicity in a dose‐dependent manner.

Protein transport across the lung epithelial barrier.

This review provides an update on recent findings on protein transport across the alveolar epithelial barrier and reveals that albumin and IgG are absorbed via saturable processes at rates greater than those predicted by passive diffusional mechanisms.

A microfabricated array bioreactor for perfused 3D liver culture.

It is observed that preaggregation of the cells into spheroidal structures prior to seeding improved the morphogenesis of tissue structure and maintenance of viability.