Your body is one of the most complex natural structures ever. Billions of cells are put together in a specific way with the result being you. If you look closely between the cells you'll find the extracellular matrix, a gel-like environment where cells reside and which helps them to talk to each other. However, when disease strikes, cells and the matrix alike can be irreparably damaged, which could lead to the loss of cell function. In her PhD research, Maritza Rovers looked at ways to make microgel-based scaffolds for cells, which could be used to support eye cells or even promote nerve growth in spinal cord injuries.
Every person on the planet is made up of billions of cells, which are the building blocks of our bodies. Between these cells lies the so-called extracellular matrix (ECM), a gel-like environment in which cells live out their lives.
"The matrix provides stability and facilitates communication between the cells and the matrix itself," says Rovers , who defended her PhD thesis at the Department of Biomedical Engineering on December 17. "When disease occurs though, the ECM can be damaged and the cells too. However, sometimes the body cannot repair the damage, which leads to loss of function for the cells and the organ where the cells are located."
Becoming a scaffold builder
Motivated to help cells heal better when disease strikes, Rovers decided to become a scaffold builder for her PhD researcher, creating structures that mimic this complex ECM.
"I didn't decide to build the metal ones that you see ones around houses under construction," says Rovers with a smile. "Instead, my aim was to build scaffolds from molecular building blocks that support human and plant cells, as well as helping them to grow."
To realize such scaffolds, Rovers turned to the world of supramolecular chemistry, which uses synthetic building blocks (known as monomers) that self-assemble into networks. "The networks or scaffolds formed lead to hydrogels with properties that mimic the ECM."
However, such hydrogels are often quite dense or bulky with limited spatial control. "The natural ECM is finely regulated by processes at various length scales and bulk hydrogels can't always capture this. Microgels, as small building blocks for larger scaffolds, offer a solution to mimic the ECM," says Rovers.
Microfluidic origins
Creating these supramolecular microgels involved the use of droplet-based microfluidics, which is a technique where tiny droplets of water are formed inside an oil phase. Eventually this gelates into a microgel.
"Taking this approach allowed for the careful modulation of the microgel properties by varying the concentration of building blocks, crosslinkers, and bioactive peptides," points out Rovers.
"These tiny supramolecular building blocks are like different types of K'NEX toy building blocks. With the same K'NEX blocks you can create a whole range of different designs. It's the same for the supramolecular building blocks - we can create a range of structures, each with completely different purposes. I worked on creating small micro-building blocks (microgels) from these molecules that could be used for different types of cells."
Applications aplenty
Which cell types did the young researcher want to help with her new scaffolds? Well, with plenty of expertise on supramolecular chemistry and applications to be found in the lab of Patricia Dankers - Rovers' supervisor, she had plenty of colleagues to work with on various applications.
"Together with my colleague Annika Vrehen, we combined our research efforts. Annika worked on a replacing synthetic matrix to design a microenvironment in which cells from the stroma - the thickest layer of the cornea - could live and survive. We encapsulated the cells she used in my tiny microgels. We observed that the cells were able to escape from their microgel and interacted with other neighboring microgels and cells."
"The cells started to use the microgels as building blocks to build their own tissue structure. This was completely autonomous, and cells were able to organize this themselves."
In addition, Rovers used the same building blocks to create microgel scaffolds to help grow nerve cells after a spinal cord injury and to even cultivate plant cells.
Challenging plant cells
For Rovers, the biggest challenge was growing plant cells. "When we started, we thought it would be easy. Unlike humans, plants grow everywhere, and if you prune them, they grow back. That's obviously not the case for the human body. However, it turned out to be more difficult than expected - plant cells were much harder to grow in the lab because they are so fragile."
Eventually, Rovers and her colleagues did manage to get the plant cells to grow in combination with their supramolecular-based materials.
"We tried to show that while it's still far from ideal, the field of plant cultivation can learn a lot from biomedical tissue engineering and regenerative medicine. And vice versa, of course!"
Learning how to act
During her PhD journey, Rovers gained many new lab skills and learned how to work independently, but she highlights something else as being more significant.
"The biggest change that I saw in myself was learning to act and just start, instead of overthinking everything before doing anything in the lab. In the first year of my PhD, I would try to plan out every step in the lab. But this doesn't work as things don't always go as planned in the lab. Experiments go wrong, and it's in those moments that you learn to adapt and arrive at creative solutions. These aren't skills that you can learn by sitting at the desk and overplanning."
In addition, the researcher notes the importance of finding balance and letting go of things that are outside one's control. "Perfectionism is a good thing to have in research, but it shouldn't dominate. I'll keep reminding myself that for the rest of my scientific career."
After spending four years working with cells, Rovers is planning to continue making advancements in the world of the small. "I'll stay with my current research group after my defense for a short period. After that I want to go abroad for a postdoctoral position. But there are factors that aren't entirely within my control, like securing grants. Nonetheless, I'll put in my best effort and look to the future with optimism."
Title of PhD thesis: Engineering supramolecular microgels into artificial matrices. For applications in human tissue engineering and cellular agriculture . Supervisors: Patricia Dankers and Marcel van Genderen.
