Drug development can take years and even decades, along with billions of dollars, just to release a single new drug to the market . Current drug development involves an integration of animal testing with expensive and inefficient clinical trials. What if there was another way to develop drugs that would save time, money and would eliminate – or at least lessen the need for – animal models in research and development? Organs-on-chips technology has the potential to answer this question and solve these issues.
Organs-on-chips (OoCs) are a relatively new technology and a promising alternative for current models in drug development. An OoC device is a small apparatus approximately the size of a USB thumb drive, lined with living human cells, which mimics breathing motions and muscle contractions through small fluidic channels. OoCs are also known as microphysiological systems or tissue chips . Not only can OoCs help accelerate drug research and development, but they also have the capability to provide researchers with a better understanding of normal human body function and metabolism.
As explained in the research paper, “Organs-on-chips: into the next decade” by Low et al., there are many problems with the way drugs are currently being developed. The processes by which clinical trials are performed are very time-consuming, taking months or even years to complete. Drug development is also not cost-effective; thus, an alternative that is cheaper and quicker to perform tests would benefit the drug development field drastically. Furthermore, there are many differences between animal and human studies that do not directly translate, which can be problematic when transferring data learned from animal models to human clinical trials .
OoCs are not the first technology to attempt to artificially recreate human body systems on a small scale to model organs and their functions and interactions. One of the first models was a “heart-lung micromachine,” which involved the combination of a lung cell culture model and a cardiac device. This microdevice was engineered with the goal of observing and analyzing how aerosol drugs delivered to the lungs affect cardiac function . “Lung-on-a-chip” is another early model of artificially created human body systems. Research for this technology was published in 2010 and it was one of the first microdevices that was created to contain human cells and tissues, and was made to model organs and their functions .
One key feature of OoCs that make them unique from other microdevices is their range of size. OoCs can range from the size of a USB thumb drive to larger devices that are the size of a standard 96-well laboratory plate. These larger devices can model multiple organs at once and mimic how organ systems interact and respond to various stimuli. There are a few defining characteristics of OoCs: the 3-D form and organization of tissues, the combination of many cell types and biomechanical forces. First, the 3-D form and organization of tissues on the device allows for different tissue types to be accurately represented. For example, transwell systems, which are inserts used in cell culture, allow the OoC to model barriers and fluid flow across a permeable membrane. Another unique aspect of OoCs is the combination of many cell types to “reflect a more physiological balance of cells (such as parenchymal, stromal, vascular and immune cells)” . This provides a more accurate model for certain tissues because the interactions between different cells are considered. Finally, OoCs contain “biomechanical forces” that allow the tissue being modeled to be more accurately represented. For example, if an OoC is modeling lung tissue, stretch forces will be present, just as in real lung tissue in the human body. These biomechanical forces are built into OoCs to model fluid flow by using microfluidic channels that act as “engineered vasculature” and can bring nutrients and fluidic flow to cells .
While this all seems too good to be true, OoCs are not without obstacles and challenges. One challenge that bioengineers have come across is the complexity of the human body and the intricate and precise processes required to model and mimic these physiological control systems into one of these microdevices. OoCs can model key aspects of a specific type of tissue; however, these devices cannot mimic an entire human tissue or organ that is fully functional in and of itself. Another issue is renewable cell sourcing due to the limited amounts of primary cells. To combat this, iPS cells, which have an unlimited source of cells, and adult stem cells are used, thus allowing all tissues in a multi-OoC platform to come from the same donor .
Overall, OoCs have incalculable potential in the drug development field as well as in the medical field as a whole. One future direction of this technology is developing a “Patient-on-a-chip,” which is a way of disease modeling on microdevices with a patient’s unique body systems. Using OoCs as unique patient-specific models dependent upon a patient’s characteristics drives OoCs towards the field of precision medicine. OoCs can model diseases like angiogenesis and tumor growth and can even act as cancer models. An example of such an instance is OoCs with patient-derived tumors treated with chemotherapy that have allowed for the comparison and optimization of treatment types for actual patients . In the future, as drugs are developed and patient-specific treatments are optimized, OoCs will continue to streamline and make processes more efficient and accurate, allowing for groundbreaking improvements in drug development and precision medicine.
Edited by: Neha Adari
Illustrated by: Neha Adari