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.
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. Organ-on-a-chip has been widely used to simulate lung physiology and pathology. (Nawroth, 2018)
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. Microenvironment and cellular component of Lung. (Bennet, 2021)
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. Epithelial cells and endothelial cells were seeded into separate channels to form a non-contact co-culture. (Lee, 2022)
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. Vacuum chamber design recreates cyclic stress stimulation of lung cells. (Huh, 2010)
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.
For Research Use Only. Not For Clinical Use.