In a world of nanotechnologies and microchips, the ability for large-scale processes to take place on the microscale are becoming increasingly prevalent, even in the environment of combating chemical and biological threats to our warfighters. A research effort by the Defense Threat Reduction Agency’s Joint Science and Technology Office, Los Alamos National Laboratory (LANL) and Wake Forest University (WFU) has resulted in an award-winning miniature technology in the eX-vivo Capability for Evaluation and Licensure (XCEL) program, the Pulmonary Lung Model (PuLMo). Commonly referred to as an “organ-on-a-chip,” the model will offer faster and less expensive processes for drug delivery to our warfighters facing chemical and biological threats.
In order to bridge the gap between in vitro human assays, animal testing and clinical trials, this new technology allows researchers to assess real-time drug interactions on key human organs during the development of medical countermeasures. The PuLMo uses a unique combination of miniaturized organoid constructs derived from human cells to engineer an advanced 3D system that mimics four vital human organs (heart, lung, liver and kidney) either alone or in integrated circuits. To assess damages, these 3D human organoids are exposed to drugs, drug metabolites, chemical and biological agents or other toxicants.
For example, if a drug or its metabolite demonstrates an adverse effect on organ tissue that was not identified during animal testing, scientists can reassess the compound structure and other metabolic attributes to mitigate the risk factor. In addition, the ability to test multiple compounds rapidly offers the potential to mitigate safety risk without extensive animal testing. The FDA and other regulatory authorities view this as an important step in reducing animal use and improving our understanding of compound liabilities.
Recently, DTRA’s JSTO, WFU, the Space and Naval Warfare Systems Command, the U.S. Army Medical Research Institute for Infectious Diseases, the National Institutes of Health and the FDA participated in the first demonstration of this technology. Scientists at LANL validated the remarkable progress on each of the miniature organoid constructs, which incorporates both airway-type cells and alveolar cells, each with different morphology and functionality.
To mimic the structure of the human lung, the PuLMo team developed two different lung models. The first model focuses on tissue engineering and co-culture of multiple cell types and consists of two major units—bronchiole and alveoli. These units are connected via a microfluidic chip, known as a Fluid Circuit Board, to help manage the flow of air and media.
The second model focuses on mimicking the air-flow dynamics in the human lung and tissue engineering. It does not have a Fluid Circuit Board, but the model mimics the branching of the late generations of the respiratory bronchiole and the alveolar sacs from a human lung.
Both models co-culture at least three different cell types from three different regions of the lung, the Bronchiolar Epithelial, Alveolar Epithelial and Microvascular cells. They incorporate several physiological characteristics such as air-liquid interface, ciliated cells, mucus production, cyclic stretching of membranes, surfactant production and shear flow on microvascular cells and breathing.
R&D 100 Magazine designated the PuLMo technology a Top 100 Technology Development for 2016. This prestigious award, often known as the “Oscars of Invention,” is a clear indication of the success of the XCEL program and its place on the leading edge of medical technologies.
DTRA, LANL and WFU scientists continue to be at the forefront of medical innovation by integrating, refining and expanding their capabilities in exposing key human organs with real-time evaluation of drugs and their metabolites. Additionally, unique to DoD, the organ-on-a-chip platform provides a capacity for threat agent characterization which is not possible in humans. This new capability enables researchers to deliver targeted medical countermeasures for the warfighter.
POC: Dr. Guilin Qiao; guilin.qiao.civ@mail.mil