Organs-on-Chips – A catalyst for drug testing?

According to the World Health Organization (WHO), antibiotic resistance in bacteria is one of the biggest threats to global health today. Bacteria gaining resistance is a natural process, but this has been accelerated by the misuse of medicines. The consequence of this is that bacteria remain unaffected by our current medications, leading to longer stays in the hospital, greater medical costs and increased mortality. The way to combat antibiotic resistance in bacteria is to develop new drugs that can kill them. The drug development process set by the Food and Drug Administration (FDA) is a long and costly process, coupled with uncertainty on whether a new drug will actually succeed to the next stage.

While this ensures the medicines you use are safe, the downside is that it can take decades for a drug to finally reach the shelf of your local pharmacy. To accelerate the process, scientists and engineers across disciplines are collaborating to find new drugs and drug testing methods. One such group is Emulate Inc., a Wyss Institute (from Harvard University) start-up.

In April of last year, the FDA announced that they are entering a multi-year research and development agreement with Emulate Inc. They will be evaluating their Organs-on-Chips (OOCs) technology to check if they can be used in the drug testing process. There are three components to OOCs: Organ-chips, instrumentation and apps.

“Antibiotic resistance in bacteria is one of the biggest threats to global health”

The organ-chips are the size of an AA battery. They are lined with living human cells and have microfluidic channels that can allow the flow of air or blood, just like in the human body. The chips are flexible, allowing motions like breathing or muscle contraction to be simulated. They are also transparent, allowing researchers to analyse the organ’s functionality, behavior and response at a cellular level. Some examples of OOCs include: Blood-vessel-chips, liver-chips, lung-chips, etc. OOCs are placed inside a research system similar to a computer. The instrument is designed to recreate the environment of the human body, such as airflow. Medicines, chemicals and other toxins can be introduced into the chip via the instrument and the effect of them on the cells lining the chip can be analysed due to the modular nature of the system. OOCs can also be connected together using the instrument to better understand the interactions between different organs and the effect of foreign substances on them.

Apps help provide precise control of an OOC’s living microenvironment and configure the cell architecture amongst other functions.

Recently, a team of researchers from the Division of Hemostasis and Thrombosis at Beth Israel Deaconess Medical Center (BIDMC) collaborated with the Wyss Institute and discovered, using a blood-vessel-on-a-chip, small molecules called parmodulins. They provide anti-inflammatory and antithrombotic protection to endothelial cells without interfering with the blood clotting process. This property makes parmodulins good candidates for new drugs. Through this study, one can see how OOCs can accelerate the safer development and evaluation of drugs.

“It can take decades for a drug to finally reach the shelf of your local pharmacy”

Wyss Institute founding director Dr Donald Ingber also proposed that OOCs can replace animal testing early in the drug development process to ensure greater efficacy and safety. One of the main problems with animal testing is that the drugs are tested in cells that don’t function exactly like those in the human body. Hence, researchers need to do extensive experiments to check for potential side-effects in humans, which can take many months. According to the Nature journal, 85% of drugs fail in early clinical trials due to this. Dr Ingber proposed that by injecting drugs into an OOC, researchers can analyse the effects of the drug on human tissue itself at an early stage without potentially harming humans. However, while animals can shed light on how the drug can affect behavior, OOCs only show physiological effects of the drug on a small group of cells.

If OOCs are to become the next-generation method of drug development and research in various industries, they need to be able to be mass-manufactured and automated, ensuring that they are produced continuously with quality control. Up till now, they have been manufactured in small batches to be used in academic research.

Earlier this month, Harvard published a study in the journal Biofabrication that described a new, faster method for manufacturing hearts-on-chips. Dr Lisa Scudder, co-lead author of the study, said: “Our new heart-on-a-chip fabrication method uses a UV laser to pattern the hydrogel, employing riboflavin to sensitise the gel for optical ablation…[This] creates features on the gel much faster, but with the same resolution and reproducibility, as traditional moulding techniques.”

Dr Janna Nawroth, the co-lead author, added that the process is scalable, 60% faster than the old process, and gives uniformity without altering the hydrogel properties. This makes the technology a step closer to mass production and use by pharmaceutical companies.

Though OOCs are not yet ready to be mass-produced and distributed, good progress has been made in showcasing its potential in drug-testing, suggesting a more efficient future for the process.