01/28/2025 | Press release | Distributed by Public on 01/28/2025 16:06
During his PhD research, biomedical engineer Mohammad Jouybar explored how to build specific organ-on-a-chip or even cancer-on-a-chip devices.
When you think about cancer research, thoughts go quickly to biological tests, drug testing, and patient studies. But what if we could use engineering to discover how cancer cells manage to leave the tumor to wander through our bodies? If we know how they do that, we could stop them right then and there. The relatively new organ-on-a-chip technology allows researchers like Mohammad Jouybar to build a biomechanical model of specific cases out of the human body to closely study how cancer behaves.
TU/e researcher Mohammad Jouybar is an engineer who has been very motivated to make a difference in health care from the start of his career.
Jouybar says: "When I was looking for a PhD, the offer from Jaap den Toonder to build an organ-on-a-chip research model was exactly what I was looking for. Even though I never expected to find myself working in Mechanical Engineering as a bioengineer, it couldn't have been a more perfect fit."
"The organ-on-a-chip technology is still relatively new in the field of disease modeling and therapeutic testing. I think it's been around for about fifteen years," says Jouybar. "It is mainly gaining importance as an alternative or supplementary option for animal models. It's a more ethical and less expensive choice to gain the same insights."
Organ-on-a-chip offers a smarter, ethical, and cost-effective alternative to animal testing.
Mohammad Jouybar
"That's what intrigued me when I learned to work with the technology during my MSc studies in Milan, and why I went actively looking for a PhD to work with this technology."
In an organ-on-a-chip, researchers typically grow human organ cells in a hydrogel and/or in tiny microchannels. Because they grow the cells, they can determine exactly what type of cells they grow next to each other and what specific biomechanical cues to apply, such as blood flow within channels or mechanical stretch affecting cell-cell interaction.
Effectively zooming in on a single function of an organ or single mechanism they want to study.
You may have heard from Mohammad Jouybar before because his research pitch won him the audience award in the 2020 Dutch National Famelab competition. This annual competition stimulates young researchers to share their research with a broader audience.
"There are many startups who have jumped at the opportunity to make organ-on-a-chip, or even cancer-on-a-chip models for regular testing in clinical settings. However the industry does not have a standard organ-on-a-chip model among the available models yet. Which makes it difficult to assess and compare results."
"Also, in academia, we want to study new settings, which will always call for making innovative models. And that's what I did during my PhD."
There are several models Jouybar designed, built, and grew for his PhD. Jouybar: "My PhD was not very defined or detailed at first. The team wanted to study the metastatic phase of cancers. And that's not a single event that happens, but rather a cascade of consecutive processes."
The metastatic phase of cancer isn't a single event - it's a cascading process.
Mohammad Jouybar
In metastasis, cancer cells break away from where they first formed (primary cancer), travel through the blood or lymph system, and form new tumors (metastatic tumors) in other parts of the body. The metastatic tumor is the same type of cancer as the primary tumor.
"Jaap den Toonder asked me to design and build a model to study how breast cancer cells leave their tumor, invade the tissue, and enter the bloodstream. We wanted to study how these cells invade the bloodstream from the breast duct."
The team chose to study breast cancer - ductal carcinoma in situ -because it is very prevalent and is a good case for studying the metastatic process.
"We know that the cancer cells invade the blood or lymphatic vessels, but how some of these steps occur, especially the initial invasion steps, are not well known. And once the cells enter the blood vessel, they can travel anywhere," says Jouybar.
"We could not mimic the entire process on our chip, of course. So, we focused on the initial step of metastasis because little was known about it."
The first step is to build, or rather grow, the elements of your cancer-on-a-chip. In this case, the cancer cells are in a microchannel within the chip, emulating the breast duct, the surrounding hydrogel mimicking the structural (stromal, ed.) tissue, and the neighboring microchannels mimicking the tiny blood vessels.
Jouybar fabricated the circular cross-section channels on a chip, a similar geometry found in human blood vessels. Next, he could vary the flow through these channels to study the effect of various types of flows on blood- or lymphatic vessel cells.
"In one of our studies, I have shown that the flow rate has an effect on the orientation of cells lining the blood or lymphatic vessels we grow on the chip. The chip is 2-3 centimeters squared, but the vessels are only around 10-100's micrometers in diameter. Just like the tiny vessels in the tissue we want to study."
Growing the model to mimic living tissue is a challenge all of its own. "We had different components in the model: the breast ducts, the surrounding tissue, and the blood vessels. The trick to building the model with all those components adjacent to each other was to compartmentalize building those elements," says Jouybar.
"We used the facilities in our labs, like a femtosecond laser and 3D sugar printing, to build the circular geometries of the blood vessels. Additionally, we had to make sure that fabricated reservoirs were fully working to connect the models to the pumps for the blood flow or just simply for exchanging culture media."
In a collaboration with Amsterdam UMC, Jouybar included not only blood vessels but also built lymphatic vessels in the cancer-on-a-chip models.
Jouybar: "This was a simpler model from a fabrication point of view because we fabricated a microchannel cast in hydrogel utilizing a thin acupuncture needle. We added lymphatic cancer cells (B cell lymphoma) and fibroblasts to a hydrogel matrix."
"And then, we grew the lymphatic microvessel, lined by lymphatic endothelial cells, inside the hydrogel. With this model, we studied how donor's specific fibroblasts and lymphatic vessel cells influence the movements of cancer cells in and around lymphatic vessels."
Both models focus on the step where the cancer cells start to move from their original location, where they might still be very treatable, throughout the body. The models help to understand what is happening on a fundamental level and can also help to study which types of medicine might affect the key mechanisms of the cancer. This opens up whole new areas of drug development and treatments.
"Depending on the type of cancer you are studying, due to the broad area of oncology, you can build a model to answer questions for the specific type of cancer and tissue, or even specific patient you are studying, so-called personalized medicine," says Jouybar. "The models help us to fill in the blanks of how cancer originates, develops, and moves."
The cancer-on-a-chip models help us to fill in the blanks of how cancer originates, develops, and moves.
Mohammad Jouybar
"I really enjoy this type of collaborative research, where medical research, mechanical engineering, and biomedical engineering are colliding. We cannot do one without the other, and I expect much from how engineering can assist and boost medical research," concludes Jouybar.