Materials for cell cultures and 3D-printed organs of the future

Living cells play a crucial role in medical research, and increasingly also in therapies. But it is difficult to get human cells to behave in the laboratory as they do in the body. At Linköping University Daniel Aili is developing supporting and protective gels that can serve as an aid in a variety of applications, including cell culture and 3D-printing of organs.

Daniel Aili

Assistant Professor of Molecular Physics

Wallenberg Academy Fellow 2016

Institution:
Linköping University

Research field:
Design and construction of synthetic materials inspired by nanostructures in nature.

Researchers have been able to culture living human cells for decades. One of the simplest ways is to let the cells grow on plastic dishes – but there are drawbacks to the method. It does not work for all types of cell, and even those that grow well become less and less like the original cells over time. They acquire different shapes and behavior, and even change genetically. The cells would really need to grow in an environment that more closely resembles bodily tissue: a moist three-dimensional material with a complex mixture of biological molecules.

Aili, who is a Wallenberg Academy Fellow, is working on materials of precisely this kind. He is developing a new kind of hydrogel, which, as the name suggests, contains an ample supply of water. Hydrogels made up of biological or synthetic molecules are already used in cell cultures, and sure enough, they do ensure that cells behave more naturally. But the gels are far from perfect.

“It’s difficult to obtain the same results every time when using purely biological materials, but synthetic materials often don’t provide the right conditions for success. We want to develop easy-to-use materials that can be adapted for different applications and cells. They should also allow more scope for studying or predicting cell behavior,” Aili says.

“Being chosen as a Wallenberg Academy Fellow is more than just a matter of money – it’s a hugely valuable recognition, and opens the door to a fantastic network. I will be able to give my curiosity free rein, and delve into fascinating research questions that I hope and believe will make a difference.”

Must be liquid as well as solid

Using hydrogels that allow cells to behave as they do in real tissue makes it easier to culture cells for research, and to create “organs-on-a-chip” – advanced cultures that imitate organs at the nanoscale, and are used in drug testing. The gels could also be used in medical treatments such as cell therapy, or 3D printing of tissues or organs.

3D printing entails spraying layer upon layer of cells until they form a three-dimensional shape, whereas cell therapy involves injecting healthy cells into a patient to treat a disease or injury. In both cases the cells must be able to withstand being squeezed through a narrow tube. At present they often rupture, but if they were encapsulated in a hydrogel, they would survive intact, and establish themselves in the body more easily. This will require a material that can be both liquid and solid: fluid when the cells are encapsulated, solid so they can grow. In order to spray the material, it must also be capable of making a brief return to its liquid state, before solidifying once again when it exits the printer or spray.

“And this is what makes our gels different. They can change from solid to liquid form merely be exposing them to force in the right direction – you just pull them a little. When you stop, the molecules quickly find their way back to each other. It’s as though the material is self-healing,” Aili says.

Aili works at the Department of Molecular Physics, which has a 3D printer for biological materials. The new hydrogels have not yet been tested on it, however. The material remains costly, and is synthesized in minute quantities.

“We’re trying to get the cost down. Soon we’ll be able to print on a small scale.”

Mimicking nature’s way of keeping molecules together

Aili is not the first person to make synthetic hydrogels, but he is using completely new methods. The molecules in the material must form a stable network without binding so tightly to each other that they prevent the cells from growing or moving. His solution is based on supramolecular interactions, which ensure that the material spontaneously maintains all or part of its integrity.

“It’s extremely common in nature – for instance, this is how the two sides of the DNA double helix stay together. We are mimicking these properties by designing tiny molecules that act as a kind of dynamic glue.”

Much of the research is about gaining an exact understanding of how the molecular design influences the properties of the material and the reactions of the cells. Aili explains that the goal is to create a molecular toolbox from which the desired properties of a given gel can easily be selected.

“If you know what you want, that is. If we ask people involved in cell injection what properties they need in a gel, they are usually unable to answer. So we are working on another aspect of the process – studying how cells behave in different materials, and working out what they need.”

Aili has had an abiding interest in science and technology. His parents can still bear testimony to spillages of hydrochloric acid on the kitchen worktop, where he carried out his experiments as a boy. Neither of them were academics, but they supported Daniel. He also benefited from engaged teachers, who encouraged him and guided him onward.

“The best thing about research is to go from hypothesis to experiment, and see that the results are roughly as expected. – Or seeing something unexpected, and still managing to understand what it is. Research can really engage the emotions. It’s tough when things don’t go well, but incredibly rewarding when they do.”

Text Lisa Kirsebom
Translation Maxwell Arding
Photo Magnus Bergström