POSTED: Feb 12, 2023

Engineering
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Accelerating our drug discovery process using biomimetic Organ-on-Chips
Louis Ong

PhD (Engineering)

Queensland University of Technology

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The journey of any chemical formula from a lab to our everyday pharmacies is expensive and slow. The recipe for paracetamol was discovered in 1893, but it was only commercially available in 1950; it took 30 years before it was commercially available for consumer use. Compared to other scientific breakthroughs such as transistors, LEDs, and lithium-ion batteries, research translation of medicine still needs to be improved, not to mention expensive. From the chemist, tens of thousands of potential drug candidates are formulated. These drug candidates are then passed through rigorous screenings to check their efficacies and side effects. The candidates are first tested on in vitro (Latin for within glass) organs. They are living tissue or cells (commonly derived from tumours) in a glass dish filled with nutrient broths. These systems are less effective in identifying effective and harmful compounds, with at least 70-80% of them passing this iteration of screening. In the next iteration, drugs are introduced to mice, rabbits, and monkeys before any medicines can enter clinical trials. Compared to out-of-body (in vitro) organ models, animal models are quite effective in identifying potentially effective or harmful drug candidates because our body's cell and tissue behaviours are much more complicated than we initially thought. Changes in the cell's microenvironment, such as cell arrangements, the chemical content within their surrounding (typically maintained by the blood), the types of neighbouring cells, and even the forces that act on the cells, have a significant impact on how a cell functions and behaves. Because in vitro models cannot always mimic these body microenvironment, their sensitivities are lower than the animal models. Of course, the usage of animals for drug screening comes at a price of conflicting animal ethics with exorbitant cost and time needed. This inefficiency creates a bottleneck to the drug discovery process. A study performed by Olivier Wouters et al. in 2020 estimates that the cost of producing an approved drug requires minimally 314 million US dollars, with more prominent pharmaceutical firms' spending reaching a whopping 2.8 billion US dollars. In addition to the high cost, the drug discovery process takes 10-15 years to complete all drug trials before the licensing stage. 

Therefore, tissue engineers strive to improve our in vitro models to enhance the stringencies of this first stage of drug screening platforms. The more toxic or ineffective compounds identified in the early stages, the fewer animal tests are needed, which translates to fewer animal sacrifices and spending. In recent decades, tissue engineers have adopted microfabrication techniques for this exact purpose. Through microfabrication, engineers can create microscaled structures that can help direct and position the arrangements of cells and their surrounding fluid to match our body environment, giving birth to small scaled, highly functional in vitro organ and tissue models known as the Organ-on-Chip (OoCs). Today, OoCs representatives of critical organs include the liver, heart, muscle, kidney, skin, eye, lungs, and gut. What is fascinating about these reported OoCs is that they can be linked to form a basic system for identifying drug metabolism, distribution, and excretion (leading to the idea of human-on-chip). This feat is only sometimes achievable with traditional dish-based in vitro cultures. 

While OoCs demonstrated good signs of streamlining our drug discovery process, usage of OoCs is confined within engineering laboratories for their technically demanding fabrication process. One of my current research objectives is to simplify the manufacturing process of OoCs further to be less technically dependent while improving their compatibilities with pharmaceutical, clinical, and biological labs and industries. In my work, I have integrated many advance manufacturing techniques to deliver easy-to-replicate and consistent OoCs platforms that everyday scientific investigations can use. Furthermore, these patented OoCs can be easily scaled up, with precise control of drug and fluid deliveries and even the ability to link up multiple OoCs for a systemic understanding of drug metabolism in the body. If this work interests you, please contact me for more information and collaboration opportunities.

REF:

Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020 Mar 3;323(9):844-853. doi: 10.1001/jama.2020.1166. Erratum in: JAMA. 2022 Sep 20;328(11):1110. Erratum in: JAMA. 2022 Sep 20;328(11):1111. PMID: 32125404; PMCID: PMC7054832.


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