Lung-On-A-Chip Model Development Service

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Lung-On-A-Chip Background Typical Model Advanced Model Services Features Q&As Resources

By combining microfluidic technology with tissue engineering, Creative Biolabs has created a series of bionic lung-on-a-chip models that can be used for drug toxicity testing and disease research, providing a novel and advanced research method for related research.

Lung-On-A-Chip Model

As an important organ in direct gas exchange with the outside world, the lungs are threatened by many fatal acute and chronic diseases. In fact, respiratory diseases are directly responsible for one in six deaths worldwide, especially notorious asthma, respiratory infections, lung cancer, and tuberculosis. The lack of human lung preclinical models that can truly capture disease complexity, highly heterogeneous disease phenotypes, and in vivo pharmacokinetics and pharmacodynamics hinders the development of effective therapeutics. Commonly used animal models have difficulty recapitulating the structure and disease symptoms of the human respiratory system. With an in-depth understanding of tissue engineering and a precision processing technology platform, organ-on-a-chip has become the best choice for recreating key functions and microenvironmental characteristics of human organs in vitro. Well-constructed lung structural units provide powerful tools for disease modeling, drug discovery, and drug testing for the development and study of human respiratory diseases.

Fig. 1 Schematic of body on a chip system. Fig. 1 Organ-on-a-chip has been widely used to simulate lung physiology and pathology.^1,3

Microenvironment and Key Features of Lung

Building a lung-on-a-chip is not about reconstructing and replicating an entire human lung with its complex structure. In fact, this is still not technically feasible. The advantage of lung-on-a-chip is that they can be engineered and recreated with well-defined functional units of the lung. The lungs are composed of trachea, bronchi, small airways, alveoli, blood vessels, and lymphatic tissue. Altogether, the lung is composed of approximately 40 different cell types, with the pulmonary epithelium forming the critical air-liquid interface and connecting goblet cells, ciliated cells, and various basal cells. The most common lung chip construction strategy is to first focus on epithelial cells, and then build multicellular structures by merging and adding other cell populations.

Fig 2 Schematic of microenvironment and cellular component of Lung. Fig. 2 Microenvironment and cellular component of Lung.^1,3

Typical Lung-On-A-Chip Model

A typical lung-on-a-chip usually focuses on characterizing the alveolar structural unit, and reconstructs the boundary between lung air sacs and their capillaries through microfabrication to construct a unique air-liquid interface (ALI). Our basic lung chip is divided into two parallel channels by a flexible, ECM-coated porous membrane. This design supports the growth of epithelial cells at the ALI, while human lung microvascular endothelial cells are located on the other side of the basement membrane and exposed to a continuous laminar flow of the medium, allowing the formation of airway tubules maintained by surrounding endothelial cells. The segmented channel configuration allows independent manipulation of fluid flow and transport of cells and nutrients to the epithelial and endothelial cell layers, respectively. This design simulates and reproduces the key structural, functional and mechanical properties of the human alveolar-capillary interface, maintains cell-cell interactions and airway function, and enables visualization of cell experiments under diseased and therapeutic conditions.

Fig 3. Non-contact co-culture of epithelial cells and endothelial cells. Fig. 3 Epithelial cells and endothelial cells were seeded into separate channels to form a non-contact co-culture.^2,3

Advanced Lung-On-A-Chip Model

The challenge in building more advanced lung-on-a-chips lies in faithfully recapitulating the structural and functional elements of human tissue that control healthy and pathological organ responses. The lungs achieve a constant supply of oxygen by inhaling air, during which cells are subjected to uniform mechanical strain. Thanks to our strong technology platform, Creative Biolabs can customize lung chips with various structural and functional modules for our clients. Soft lithography combined with chemical etching can build a vacuum chamber on both sides of a conventional lung chip. By integrating with a vacuum device, cyclic stretching of the tissue interface is achieved to generate uniform and unidirectional mechanical strain to simulate the physiological breathing process. Since respiratory diseases do not only affect the alveoli, the complexity of the lung-on-a-chip model in replicating various aspects of the lung also increases with the deepening of pharmaceutical or biological research, and this process often includes more structural simulations, cell phenotypes, and interaction relationships.

Fig 4. Organ-on-a-chip used to simulate lung physiology and pathology. Fig. 4 Organ-on-a-chip has been widely used to simulate lung physiology and pathology.^2,3

Our Services

The huge variation in cell type, function, and tissue morphology between different lung regions and disease states is an important parameter for designing human lung chips, which means that it is unrealistic to use a single model as a suitable tool for all research. Here at Creative Biolabs, we can not only provide you with simple but practical basement membrane lung chips, but also customize a suitable lung chip according to your experimental plan. By creating a simple and well-characterized base model, we enable the construction of lung-on-a-chip by adding cellular components and structural units. Depending on the experimental question, our model will generalize and reproduce the key morphological and functional characteristics of your desired organ unit. Our chips and designs have been used to model lung disease, study immune cell recruitment, assess mechanical stress and cell damage, and test drug efficacy and toxicity, so don’t hesitate to contact us for more information.

Features and Benefits

Realistic Physiological Simulation

Our lung-on-a-chip model replicates the lung's microenvironment, including the alveolar-capillary interface and mechanical breathing motions. This realistic simulation enhances the accuracy of drug testing and disease modeling by providing a closer approximation to human lung function than traditional in vitro models.

Customizable Microenvironment

Researchers can customize the lung-on-a-chip model to study specific conditions or diseases by adjusting the types of cells and the mechanical properties of the microenvironment. This flexibility supports a wide range of research applications.

Versatility in Applications

The lung-on-a-chip model is versatile and can be used for various applications, including toxicology studies, nanoparticle research, and the evaluation of inhalation therapies. Its adaptability makes it a valuable tool in multiple fields of respiratory research.

Integration with Advanced Technologies

The model can be integrated with advanced imaging and analytical techniques, such as high-resolution microscopy and biosensors, to provide detailed data on cellular and molecular processes within the lung microenvironment.

Scalable and Reproducible

The microfluidic design ensures that the lung-on-a-chip model is scalable and reproducible, supporting consistent results across different experiments and facilitating large-scale studies required in drug development.

References

Bennet, T.J.; et al. Airway-On-A-Chip: Designs and applications for lung repair and disease. Cells. 2021, 10: 1602.
Lee, D.F.; et al. Development and evaluation of a bovine lung-on-chip (bLOC) to study bovine respiratory diseases. In Vitro Models. 2022, 1: 333-346.
under Open Access license CC BY 4.0, without modification.

Q&As

Q: What diseases can be studied using the lung-on-a-chip model?

A: The lung-on-a-chip model can be used to study various respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and infections like COVID-19. It allows researchers to observe disease mechanisms and test therapeutic interventions in a controlled environment.

Q: How does the lung-on-a-chip model replicate breathing?

A: The lung-on-a-chip model replicates breathing by using a vacuum to create cyclic mechanical stretching, mimicking the expansion and contraction of lung tissues during inhalation and exhalation. This dynamic environment enhances the physiological relevance of the model.

Q: What makes the lung-on-a-chip model suitable for toxicity testing?

A: The lung-on-a-chip model provides real-time monitoring and quantification of cellular responses to toxins. Its ability to mimic the lung's air-liquid interface and vascular structure allows for accurate assessment of the effects of inhaled substances and aerosolized drugs.

Q: What are the key components of the lung-on-a-chip model?

A: The lung-on-a-chip model typically consists of two microchannels separated by a porous membrane. One channel mimics the airway, while the other represents the blood vessels. This setup allows for the study of interactions between lung epithelial cells and endothelial cells.

Q: Can the lung-on-a-chip model be customized?

A: Yes, the lung-on-a-chip model can be customized to replicate specific lung conditions or disease states. Researchers can modify the cell types, extracellular matrix components, and mechanical properties to suit their experimental needs.