How MERLN creates biomedical magic

What if a complex bone fracture could heal itself? What would it be like if animal testing were no longer necessary, because we could create hearts and other organs in the lab? And what if we not only understood why we age, but could actually stop the process? It may sound like science fiction, but thanks to MERLN, breakthroughs like these are closer than we think.

The full name of the organisation is ‘MERLN Institute for Technology-Inspired Regenerative Medicine’. Regenerative medicine is a new therapy approach that helps restore diseased cells, tissues, and organs to health or replace them. Examples include heart problems and kidney diseases. The approach uses the body’s own natural healing capacity.

At MERLN, researchers from a wide range of backgrounds work together on new techniques – from chemists to biomedical engineers. MERLN is also very international: the researchers come from more than thirty different countries!

That diversity could create a sense of distance, but at MERLN the opposite is true. There is a close-knit, vibrant community where colleagues easily find common ground.

Every Friday, for example, researchers share their latest insights during lunchtime presentations. This keeps everyone engaged with each other’s work.

What if damaged tendons and bones could repair themselves? No matter how severe the damage? That is what Carlos Peniche is working on. Peniche's research aims to understand the molecular mechanisms responsible for the healing of musculoskeletal tissues, to make them heal better and faster. He evaluates the use of structures made of special synthetic or biological materials. For example, imitating the structure of a tendon to improve the treatment of injuries.

Peniche places stem cells inside these structures with specific molecules. These molecules signal the cells to grow into new bone, tendon, or connective tissue. The ultimate goal is to implant these structures, containing biomolecules and living cells, into the body – precisely at the site of the damage. There, the cells set to work to create new tissue. When it comes to bones, Peniche collaborates with other researchers using not only 3D-printed structures, but also actual bone material. Using bone increases the likelihood of treatment success.

If someone has a very complex bone fracture, doctors sometimes can’t repair it. A broken arm or leg must then be amputated. Thanks to this kind of research, this may soon no longer be necessary. Peniche’s research work could also improve existing treatments. “No two accidents are the same”, says Peniche. “Every injury should receive a custom-made approach. That’s what we’re working on.

To conduct effective research at MERLN, scientists need materials that are as close as possible to real human tissue. That is why they often work with hydrogels: polymers that contain a lot of water, just like the tissues of the human body. Anna Pierrard is investigating how she can make these hydrogels truly lifelike.

“In my research group, we are trying to develop dynamic hydrogels”, explains Pierrard. “These are gels whose properties can change over time. Just like in the human body, where tissues are constantly in motion and adapting.”

Researchers can make the hydrogels softer or stiffer by changing their properties to match different target tissues. After all, cartilage feels very different from a kidney. The ultimate aim is to place hydrogels inside the body to replace damaged or lost tissue. For example, cartilage in the knees, which doesn’t fully regenerate itself. This could lead to better treatments for these kinds of health problems in the future.

Jaehyeon Kim is aiming to help women struggling to conceive. Through her research, it could be possible to enable better care in the future. She focuses on the fallopian tubes, a part of the female body that remains under-researched. “A lot of research has always been done on the uterus, because that’s where the baby grows", says Kim. “But fertilisation takes place in the fallopian tube. That’s where the sperm and the egg meet. And that’s precisely where complications often arise, for example due to infectious diseases such as STIs.”

Kim is currently studying the isthmus, which is the first section of the fallopian tube, closest to the uterus. To do this, she is developing a model of the fallopian tube made from hydrogel. Kim is using this to investigate how STIs affect the tissue. These insights could lead to new and better treatments.

Kim hopes these results might one day help some women avoid IVF treatment. Kim: “IVF can be a good solution, but the success rate is relatively low, it is expensive and can be very emotionally draining. We therefore hope to identify the cause of certain fertility problems so that we can treat them directly.”

Research on human embryonic development is important. Scientists want to know, for example, how an organism develops in a healthy and diseased context. However, you cannot simply carry out such research using real human embryos, as this raises ethical questions. That is why Anna Peeters and Leila Ashtar at MERLN are working on alternative methods. They are creating simplified models of various embryonic stages from stem cells in the lab, without the use of sperm cells and eggs. Moreover, Peeters and Ashtar study the effects of chemicals, pollutants or medicinal drugs on early embryonic development. By gathering all this information, they also aim to improve fertility treatments such as IVF in the near future.

Their research group produces customised cell culture tools, including thin polymer sheets with grooves smaller than a human hair. They place a determined number of stem cells into these grooves to form small clusters. Together with a specific cocktail of chemicals, these clusters of stem cells form structures that are very similar to structures found during human embryonic development. For example, human blastocysts around five to six days after fertilisation.

“These are some of the techniques that allow us to study specific aspects of early development of a human embryo for the first time without using actual embryos”, explains Ashtar. “This opens the door to more extensive research.”

Ezgi Çevik is developing a truly unique 3D printer. It will soon enable her to print heart tissue. But this is no simple process. To bring heart cells together into a single complex tissue unit, she uses a combination of magnets and sound waves. By doing this, she literally makes heart cells hover towards each other!

Çevik’s printer is designed to help MERLN assemble organoids. These are miniature organ models made from multiple stem cells used to simulate diseases and test treatments. “At the moment, I’m focusing on the heart”, she says. “But ultimately, my device will be able to print all the body’s tissues.”

Çevik’s 3D printer uses two techniques to bring the cells together: magnetic and acoustic levitation. “In magnetic levitation, I place the organoids in a chamber between two ring magnets with the same poles facing each other”, explains Çevik. “This causes them to float towards the centre and come together there.”

Using acoustic levitation, she brings the cells together with sound waves. “When two sound waves with the same properties travel towards each other, you can make particles hover between the waves”, she says. “This allows you to trap them together and even move them.”

A baby’s heart works differently from that of a 65-year-old. Cells change as we age. Because heart problems often arise later in life, it is important to research adult heart tissue as well. However, lab-grown tissue must age naturally, a process that takes decades. That is why Alix Lemaître is developing methods to create adult heart tissue directly. Her colleague João da Silva Ribeiro is taking it a step further: he is investigating how they can develop tissue that resembles that of elderly people.

With these ageing heart models, researchers can test medicines and treatments more effectively. That is why Da Silva Ribeiro is focusing on unravelling the ageing process. Why do we grow older? What causes it? And how can you replicate that process in the lab?

“We actually know surprisingly little about that”, says Da Silva Ribeiro. “If we understand better how ageing works, we can also find ways to slow it down or stop it. That could have a significant impact on all age-related diseases. And who knows? Perhaps one day we might even be able to reverse the process.”

Photography: Paul van der Veer | Text: Caya Forman