Story | 04/26/2023 09:52:00 | 9 min Read time

Human cells are now grown in wood – and in the future, that could save your life

Johanna Puustinen

Writer

Finnish cellulose is now being processed into a unique supermaterial that can be used to develop new medicines and solve the environmental challenges of manufacturing. Birch nanocellulose benefits cancer patients, laboratory animals and the domestic forest industry.

Tijmen Booij is a Dutch biomedical doctor and scientist whose workplace is where cells grow in wood – Finnish birch trees, to be precise.

Booij leads a research group on automation at ETH Zurich’s technology platform NEXUS Personalized Health Technologies, which provides technology services and tools for medical researchers. In his laboratory, large robots pipette drugs onto plates where hundreds of cell clusters are embedded in a gel-like substance and grow side by side. The cells are derived from tumours of cancer patients, and the robots are used to test how different drugs work on them.

A cancer drug proven to work in the laboratory can save lives, but it takes hard work to screen new drug molecules. Booij's team's mission is to find ways to make drug research more efficient through technology. Automation robots are one answer to this need. 

"Cell samples isolated from humans are a very important and valuable material for medical research, but they are difficult to obtain. It is therefore important to be able to carry out experiments on a miniature scale – we are talking about microlitres. This allows us to do more science with fewer resources," says Booij.

What does birch have to do with all this? The hydrogel in which the precious cells grow is made of only wood and water. In cell culture, cells isolated from tumours cannot survive long outside the human body without right growth conditions. The hydrogel, together with specific growth medium, supports the cells when grown outside the human body and provides them a suitable three-dimensional environment to grow and multiply. Without supportive growth conditions, no cell-based research could be done. The hydrogel, together with specific growth medium, supports the cells when grown outside the human body and provides them the right conditions to grow and multiply. Without supportive growth conditions, no cell-based research could be done.

The most valuable thing you can make from pulp

You cannot make cell culture hydrogels from just any wood fibers. Its secret is nanocellulose, which is pure cellulose processed to the highest degree. Nanocellulose is essentially the same material as ordinary pulp used to make paper, but, as its name suggests, it is processed down to a much smaller size.

"When wood cellulose fibers are broken down to the nanoscale, millimetre parts per million, its properties change radically," says Tony Kiuru, Senior Manager, Business Development at UPM Biomedicals, a cell culture hydrogel manufacturer.

Thanks to its exceptional properties, nanocellulose has the potential to address painful environmental issues in many challenging industry sectors. It is stronger by weight than any steel grade, and its absorbency and thermal insulation properties outperform many traditional materials used in industry. In recent years, researchers have predicted that nanocellulose could be used in applications such as  a raw material for wood-based electronics and  as a biodegradable packaging material.

Nanocellulose has the potential to address painful environmental issues in many challenging industry sectors.

In medicine, gel-based cell culture suitable biomaterials have traditionally been made from animal and synthetic materials. Using products of animal origin means sacrificing laboratory mice. Synthetic biomaterials, on the other hand can be used as well, but usually the materials are not as biocompatible and might contain fossil-based ingredients. The nanocellulose hydrogel is made from renewable raw materials and is completely animal-free, which has also been welcomed at Tijmen Booij's workplace.

"Some cells require a more robust, collagen-based growth environment than nanocellulose, so the medical industry cannot give animal-derived materials up entirely. But we should replace them with animal-free ones whenever possible," he says.

If the use of nanocellulose were to increase in other sectors, it would also boost the productivity and prosperity of the Finnish forest industry. Cell culture hydrogels are an interesting precedent. While you can buy a kilogram of traditional pulp for €1, a five-millilitre syringe of nanocellulose hydrogel costs €160. The price per litre is therefore €32,0000, making it the most expensive product that can be made from pulp.

"In medical applications, the wood raw material is therefore given the highest possible added value," says Kiuru.

 

Nanocellulose boosts painfully slow drug development

Let's head back to the Swiss automation laboratory. According to Tijmen Booij, cancer treatment is by no means the only medical process that could benefit from automation. Automation is urgently needed, because the development of all kinds of medicines and treatments is currently very slow and expensive. A single drug molecule can take ten years and billions of euros to develop. 

"Out of the tens of thousands of compounds tested, only one may end up on the market. It takes a lot of time to test these compounds manually, but robots can be used to do more testing at the same time. They also don't make human errors," says Booij.

According to Booij, wood-based cell culture hydrogels have properties that make it more suitable for automated drug discovery than other alternatives. Robots cannot improvise, so they benefit from the uniformity of the nanocellulose hydrogel. Unlike animal-derived hydrogels, nanocellulose hydrogels don’t solidify at room temperature conditions, allowing them to be easily and reproducibly handled by the pipetting robots, without additional temperature control in the lab. With animal-derived hydrogels the instruments and plastics need to be cooled down to avoid unexpected solidification of the gel that would cause variation in results and losing precious lab reagents.

The growing popularity of automation will soon be reflected in the everyday lives of ordinary people.

Automation can streamline the laborious early stages of drug development. Robots can be used to carry out high-throughput screening – massive experiments that test the effects of tens or even hundreds of thousands of different compounds on a desired tissue type or organ. Experiments can use three-dimensional tissue and tumour models grown on nanocellulose hydrogels to reliably simulate different parts of the body or disease. Of the compounds tested, the most effective ones are selected for further development.

“Being able to identify compounds that would fail in clinical trials as early as possible would save a lot of resources. Medicines could be brought to market faster if the use of 3D cell models were increased," says Tony Kiuru from UPM.

Booij also believes that the growing popularity of automation will soon be reflected in the everyday lives of ordinary people. For example, cancer patients may in the future be offered treatment recommendations based on automated drug screenings using their own tumour cells. The laboratory could test exactly which drugs work best on the patient's own tumour. Here again, the nanocellulose hydrogel would play a role as an enabler of research.

"But this kind of research is still in its infancy and there is still a lot of room for improvement in the technology involved," says Booij.

Future 3D-printing of organs using nanocellulose

UPM is currently the only forestry company in the world that produces nanocellulose for medical research. Initially, the company investigated the suitability of the material for traditional forest industry applications, such as modifying the strength of paper. Then the direction changed.

"In the early 2000's, we were looking for uses for nanocellulose in collaboration with Aalto University, the University of Helsinki and the Technical Research Centre of Finland (VTT). That's how we realised that the most interesting new opportunities for nanocellulose are actually in medicine," says UPM's Tony Kiuru.

The suitability of nanocellulose hydrogels for cell culture was discovered at the University of Helsinki. The breakthrough was soon granted a patent.

UPM continues to actively explore the potential of nanocellulose in medicine and beyond. In recent years, UPM has had around 60 different development projects in the field of medicine.

Bioprinting is still a very young field, but in the future it may even be possible to bioprint skin or implants.

In Finland, UPM has participated in a multi-year Cancer IO research project coordinated by the University of Helsinki, which brought together leading cancer researchers, representatives of the pharmaceutical industry and patient organisations. The project developed novel solutions to enhance advanced immunotherapy for cancer. It is a form of treatment that uses the body's own immune system and is rapidly gaining ground alongside traditional surgical and drug treatments for cancer. Nanocellulose was used in the project to grow tumour models.

"The project was a great example of how academia and industry can join forces to research and develop new things," says Tony Kiuru.

Through collaborative research, several new uses have also been found for nanocellulose, some of which have already been commercialised. Among other things, UPM produces wood-based bioinks that can be used for 3D printing of tissues. In 3D bioprinting, the nanocellulose provides a supportive structure for the cells from which the printed tissue is built. Bioprinting is still a very young field, but in the future, it may even be possible to 3D bioprint skin or implants.

 
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