Chronic wounds are a big problem for patients with more severe types of diabetes or other diseases. Such wounds, which can be found in feet, sores and other parts of the body, are difficult to heal and the microorganisms that cause them can eventually become resistant to antibiotics.
How can we do more to help these people? A team of Lithuanian, Norwegian, Latvian, Latvian, Estonian, Spanish and Israeli researchers is planning to develop an effective and environmentally friendly medical device - a healing patch in the form of a gel that can be injected directly into the wound.
Dr. Wanessa Melo and Dr Arūnas Stirkė, chemists in the Department of Functional Materials and Electronics at FTMC, will be making an important contribution to this idea. "The aim of many conventional patches is to protect the wound from the outside. Ours will work from the inside, which we hope will make it more effective," say the Lithuanian scientists.
(Dr. Arūnas Stirkė. Photo: Hernandez & Sorokina / FTMC)
One idea failed, but the door was opened for another
It all started a few years ago, when a joint team of scientists had a different idea. A. Stirkė recalls that he and his foreign partners were applying for the Baltic Research Programme project "Sustainable and innovative technologies for better utilisation of by-products from marine and dairy industries".
By-products are materials that are left unused during food production and not intended for human consumption, such as animal hides, skins, bones, fish heads, etc. However, these products can still be useful for other purposes if properly processed. This was also the task of the scientists we mentioned.
"We wanted to look for new technologies to improve the yield and extraction of useful substances (such as protein) from salmon or other by-products. We also wanted to see how our method affects certain dairy by-products such as cow colostrum or whey," says Arūnas.
Four research institutions were brought together for this project, each with its own role to play. The first was the semi-private Norwegian institute SINTEF.
"One of its departments is based in Trondheim, on the Atlantic Ocean. The two Lithuanians working there are involved in research on chemical extraction (extracting useful substances) from a wide range of marine life," says the chemist.
So the Norwegians were to be one of the by-product suppliers in this project. The other partner suppliers were the Latvia University of Life Sciences and Technologies, who work with by-products of the dairy industry. They are trying to extract proteins or other components from dairy whey and "feed" them back into the food chain or to develop higher value-added components for the chemical industry. In addition, Latvians are renowned for their research on cow colostrum and whey - and are looking for ways to extract certain active molecules from this material.
FTMC Department of Functional Materials and Electronics, and more specifically Dr. Arūnas Stirkė, is working on an environmentally friendly and innovative extraction method. He uses Pulsed Electric Field (PEF) technology, whereby lightning-fast (one million times shorter than a second) high-voltage electrical pulses are fired into liquid or semi-liquid products (located between two electrodes).
PEF holds great promise for the food industry, already helping to extract useful compounds with anti-inflammatory properties, and is used in food safety as an alternative to traditional pasteurisation methods. In addition, PEF effectively removes harmful bacteria from liquid foods such as milk and juices. The technology is faster, uses less energy and emits less CO2.
So Stirkė came up with the idea of adapting PEF's electrical pulses to better extract useful substances from fish, algae and milk by-products.
A fourth partner, the Estonian company TFTAK - a private contract research laboratory developing innovative technologies for the food and biotechnology industry to develop new products - has joined the project idea.
The Four did not win the Baltic Research Programme competition - they were one step away from funding. It seemed that was the end of all good ideas. But the Latvian Council of Science decided to keep the four-country consortium together, and gave it extra funds.
"So now we are continuing our work on this topic - we are writing an application for a larger, European project," says Arūnas. The joint team's goal is to win the EU4Health competition for the project "Nano and advanced technologies for disease prevention, diagnosis and therapy" (NANOTECMEC).
To give the application even more weight, the consortium of Norwegians (this time no longer SINTEF Institute, but Grøntvedt Biotech AS), Lithuanians, Latvians and Estonians also brought in specialists from Spain - scientists from the Polytechnic University of Catalonia, who have experience in developing next-generation injectable patches. Another Estonian company, Nanordica Medical, is also planning to join.
In addition, if the application is accepted, the Sheba Medical Center, the largest hospital in Israel and recognised as one of the best in the world, will contribute to the project.
(Dr. Wanessa Melo. Photo: Hernandez & Sorokina / FTMC)
The "fighting duo" of nanoparticles and proteins
So what is the new idea of the joint research team? W. Melo explains it in more detail:
"Our main goal is to create an injectable patch from animal by-products that hardens in the wound. It would be antibiotic-free, but enriched with at least two active components - niobium pentoxide nanoparticles and certain proteins extracted from by-products.
Niobium is a chemical element, one of the metals. We create these nanoparticles ourselves, in the laboratory of the Department of Functional Materials and Electronics. And the Latvia University of Life Sciences and Technologies has done a lot of research on milk by-products and found that the proteins extracted from milk (especially lactoferrin) have very active anti-inflammatory properties and promote cell migration, i.e. healing."
According to the scientist, the biggest culprits in chronic wounds are various microorganisms that cause inflammation, and this unpleasant process is always smouldering in vulnerable areas:
"One of the nastiest things is the biofilms that viruses or bacteria form, which make them very resistant to antibiotics. One of the main challenges is how to fight this biofilm.
Our idea is that niobium pentoxide nanoparticles would help, killing microorganisms. However, they have not been studied much and there is a challenge here. So we have an alternative: we will try silver or other metal nanoparticles, which are already used in clinical trials. We will compare the effectiveness of these two approaches in an attempt to manage the risk."
Estonian partners will carry out extensive research and Norwegian partners will supply with a food by-product - crab shells. They will be used to extract chitosan, the main source for the gel-like appearance of the injected patch.
Norwegian scientists are also considering using fishery by-products for the patch, as the organic compounds lipids extracted from them are thought to have antioxidant properties, "binding" the harmful substances emitted by microorganisms in the wound.
In addition, according to W. Melo, it is often difficult to keep wounds properly moist. So components from by-products could act like a cream - neither too dry nor too wet - to make the patient feel better.
How to "manage" nanoparticles?
So the "formula" should be: niobium pentoxide nanoparticles + dairy by-product proteins + chitosan from crab shells = next-generation therapeutic patch.
Sounds simple, but as always, the challenges will be many. The most basic one is how to make this lab-generated material stay in the wound but not enter the human bloodstream.
"We will need to attach the nanoparticle to a gel molecule. If the particle 'floats' in the wound fluid or 'lands' in the bloodstream, it will no longer be a patch, but a medicine. In this case, we do not want to create a drug, because then the gel's 'primary target' might change, and it would go to other parts of the body through the bloodstream. So, by combining all the good components into one, it will be necessary to ensure that they do not 'escape' from the wound," explains Wanessa.
(Dr. Wanessa Melo. Photo: Hernandez & Sorokina / FTMC)
Another important question to answer: what happens to the active ingredients in the patch after they have done their job? How will they dispose of them? According to A. Stirkė, this will have to be addressed in the next phase of the project (pre-clinical and clinical trials), while the current task is to develop a prototype product and test it under laboratory conditions.
The work, from idea to prototype, is planned to take three years. An artificial chronic wound will be created in a test tube in the FTMC laboratory: chemists will grow skin cells, infect them with bacteria and then scratch them to create a "wound". The scientist will mix it with nanoparticles and watch how the latter kill the microorganisms.
If successful, when can we expect a ready-to-use injectable patch? A. Stirkė estimates that this will take at least 10 years. If the initial project is successful, new partners will then be sought to carry out the mouse studies (which are very expensive, starting at half a million euros).
But a successful start would already answer many important questions.
Project national Nr. EEA-RESEARCH-59-RC
GrACE project Nr. LV-RESEARCH-0022
Written by Simonas Bendžius