Drugs that put less strain on the environment and the human body – Nanocellulose from wood to be used in drug therapies

Environmentally friendly and non-toxic nanocellulose is compatible with the human body, giving it potential to be used for a range of medical applications.

What would you say about a product for treating wounds tailored just for you? And what if targeted cellular therapy could be administered during surgical operations through a surgical suture? These methods may already become available in the foreseeable future.

For over a decade, a research group headed by Marjo Yliperttula at the Faculty of Pharmacy, University of Helsinki, has studied the applicability of nanocellulose, a natural product, to cell culture and pharmacological therapies.

“Personalised drug therapies are a growing trend which medical applications of nanocellulose could potentially boost,” says Patrick Laurén, a researcher and university instructor from the group.He focused on the subject in his doctoral dissertation entitled Biomedical applications of nanofibrillar cellulose

Where does nanocellulose originate from and what can it be used for?

Nanocellulose is composed of infinitesimal fibres that can be manufactured from either wood pulp or synthetically by using bacteria. Composition-wise, unprocessed nanocellulose resembles apple jam. What makes the material interesting is the adaptability of its structure, enabling the creation of applications for a range of uses. 

The use of nanocellulose has been studied in cosmetics, and e.g. skin care products containing nanolcellulose are in the market today. It is also used in paints and biofuels. Its utilisation, for example, in food packaging materials has been investigated at the University of Helsinki, and such nanocellulose-containing materials are in fact already available. 

The suitability of nanocellulose to pharmaceutical and biomedical use is based on the fact that it does not originate in humans or animals, but plants. Plant-based material is void of those protein structures that make the human body reject, for example, tissue grafts from other individuals.

Non-toxic and environmentally friendly material

Certain characteristics are required of biomaterials utilised in medicine. In addition to being compatible with the tissues of the body, avoiding any rejection by the system, such materials must be non-toxic. 

When nanomaterials are used in products that come to direct or indirect contact with humans, researchers want to make sure that they do not cause any degree of what is known as nanotoxicity in the human body.

“On the cellular level, extremely small materials may have unforeseen effects on the body,” Laurén explains.

He says that the researchers were surprised to find in cellular tests that nanocellulose is entirely non-toxic to cells. The effect was tested, among other methods, by placing hepatic cells, epithelial tissue from the eye and stem cells to grow in a nanocellulose gel developed by the researchers. All of the cells grew normally both in terms of shape and function. 

In addition to being non-toxic, using nanocellulose in treating humans is supported by all the trees and plants in the world being a potential source of it. Best of all, nanocellulose is an environmentally friendly material that decomposes and disintegrates naturally. 

Hydrogel as the starting point

The researchers in Yliperttula’s group specialise in nanocellulose applications manufactured from wood pulp. A significant step forward was taken in 2007 when the group thought of experimenting with cell culture in gel made of nanocellulose. At a certain stage of nanocellulose processing, the material turns into a gel-like form known as hydrogel, composed mostly of water and threads of fibre.

The nanocellulose-based hydrogel has proven to be an important innovation, among others, for drug trials. The gel provides an optimal growth medium for cells, which float around in the gel as they do in natural environments, settling into their natural three-dimensional shape as they grow. Furthermore, hepatic cells start to naturally develop bile ductules, structures resembling physiological functions. 

This is key to investigating the toxicity of drugs in the body. After being swallowed, the pharmaceutical agent in a tablet is first absorbed into the liver for processing, causing the most strain to the liver in the process. The aim is to manufacture drugs that put as little strain on the liver as possible. 

“Nanocellulose gel makes it possible to culture cells that closely resemble tissues in the body, increasing the reliability of cellular tests. This way it is easier to see whether a drug is toxic to the liver. Further development of the method will hopefully reduce the need for animal testing in the future,” Laurén says. 

UPM has since patented the hydrogel discovery in 2010 under the brand name GrowDex, and its development is still ongoing.

What happens when nanocellulose is placed inside the human body?

In recent years, the potential of nanocellulose in implant manufacture has been another focus for researchers. For his 2018 doctoral dissertation, Patrick Laurén carried out tests on a nanogel implant to be placed inside the body for drug delivery.

His investigations demonstrated that the gel implant did not migrate to subcutaneous tissue, nor did it start to disintegrate. The lack of uncontrolled transformations in the implant is important in terms of treatment, as such changes may affect its characteristics related to releasing the drug. 

What Laurén considers the most desirable outcome is to make the implants disintegrate by themselves, as the intention would not be to leave them in the body after the administration of the drug. However, the human body is unable to break down nanocellulose, which makes the development of a nanocellulose capable of self-degradation a natural next step in research. Were nanocellulose to disintegrate in the body, the end product would mostly be glucose, which is sugar. 

“Since the gel protects cells, it can be used to deliver both drugs and cells. In cellular therapy, the gel could be a potential delivery method,” Laurén says. 

Laurén has also investigated whether nanocellulose could be used in surgical sutures. He experimented with combining nanocellulose with other materials, such as alginate, a natural polymer found in algae.

A surgical suture was coated with a nanocellulose-alginate gel, to which therapeutic cells were added, with the idea of combining surgical procedures and cellular therapy with the help of the processed suture. Such a solution would make it possible, for example in the case of Crohn’s disease, to transport therapeutic cells via a surgical suture to the desired location during an intestinal operation. In this combination, the alginate self-degradas, while the hydrogel is eliminated over time through the intestine, leaving no trace of the gel in the body. 

The development of an actual treatment form is only at a gestational stage, because surgical sutures are currently coated manually. According to Laurén, a method for cost-effectively and quickly producing gel coating of uniform quality is needed.

Is it possible to print out a functional full-size liver?

Nanocellulose may also be adaptable to 3D printers. Next, Yliperttula’s research group aims to investigate the use of the material as what is known as bio-ink in 3D printers to produce structures of the body. Could bio-ink at some point in the future be used to print out, say, an entire liver? This research avenue, focused on wood-based nanocellulose, is only in its infancy. 

“Bioprinting is a growing field, and we hope to gain the ability to precisely determine the structure and features of the gel in an upcoming project. The goal is to test the functionality of nanocellulose as a bio-ink and also to look into the potential to manufacture tailored wound care products based on the wound type,” Laurén explains.

“As a biomaterial, nanocellulose has been right before our eyes all the time – we will not run out of raw material in Finland. What is needed is continued basic research on the topic,” Laurén sums up. 

Biomaterials already in use 3,000 years ago

Nanocellulose is a biomaterial, or a material compatible with the human body. The use of biomaterials in treating humans is by no means new. A female mummy found in 2000 in Egypthad a prosthetic toe made of wood that had been designed and fitted in an anatomically correct way, making her able to wear sandals. The mummy is 3,000 years old, which makes the prosthesis the oldest known biomedical device in the world. 


Plant-based nanocellulose

Nanocellulose consists of infinitesimal fibres that can be extracted from wood and plants. 

Wood is composed of xylem, which in turn is composed of various fibres, mostly cellulose. Cellulose can be processed with a number of techniques, of which the most common is mechanical grinding. As a result of this processing, cellulose turns into wood pulp resembling in its consistency a gel-like mulch. 

After this, the processing can continue: the fibres can be made even smaller by running them through various machinery. This process can be combined with an acid treatment which advances and catalyses the degrading process, or an enzyme treatment which also detaches wood cells from each other. 

As the fibre size decreases, bundles of microfibres start to come off from the cellulose mass, resulting in nanofibres. These fibres have many names: nanocellulose, microcrystalline nanofibres and micronanocellulose.