The future of burn research: how cultured skin is replacing laboratory animals

In the Burn Research Lab, the research laboratory of the Alliantie Brandwondenzorg Nederland in Beverwijk, researchers work with cultured skin to investigate burns and treatment methods. This innovative approach saves dozens of laboratory animals each year and, according to researcher Patrick Mulder, offers a model that is closer to human reality.

About eight years ago, the research team in Beverwijk decided to stop using laboratory animals. Since then, they have mainly worked with human cells and tissues. “We use blood and residual skin from operated patients. With these real, human burns, we get a good picture of what happens in the body,” says Mulder. Nevertheless, that is not always enough to fully understand the complex reactions. That is why the researchers recreate human skin in a cultured skin model in order to better study the biological processes.

The idea of cultured skin originally arose as a medical solution for patients. “In the case of serious burns, the damaged skin is often replaced by skin from another part of the body. Nowadays, a small piece of healthy skin can be used to develop a considerable amount of artificial skin, which is then placed back on the patient’s wound. The production of artificial skin takes place at Cutiss in Switzerland, where this treatment method is already in its third clinical phase. This artificial skin delivers much better results: the skin is more supple, there are fewer scars and patients experience fewer complications.”

This medical success inspired the researchers to also use cultured skin as a research model. “We use a soldering iron to apply a controlled burn wound to small pieces of cultured skin. We then measure how quickly the wound heals and test the safety and effectiveness of medicines. This model is more relevant than laboratory animals, because human skin heals differently than animal skin. For example, wounds in animals close mainly through contraction of the wound edges. In humans, this mainly happens through filling of the wound. This is therefore a completely different process.”

Inflammation and recovery

An important aspect of the research focuses on inflammation in burns. In the case of a serious burn, the body reacts immediately. The immune system immediately sends immune cells to the wound to prevent infection and start wound healing. Three types of cells play a crucial role in this: neutrophils, macrophages and lymphocytes. “Neutrophils are the first on the scene to clear away bacteria and release substances that attract macrophages,” says Mulder. “The macrophages then take over by clearing away damaged skin and dead cells. Then the lymphocytes come into action; they offer, when necessary, a strong defense against bacteria, end the inflammatory reaction and stimulate the skin to repair itself.”

According to Mulder, in many burns the inflammatory response persists unnecessarily long, which hinders healing. He explains that this may be because there are too many neutrophils present that respond to the burn and because the lymphocytes send out too few signals to inhibit the inflammation. Recent research also shows that despite the increase in neutrophils, these cells are less effective in killing bacteria. This is probably due to their accelerated production in the bone marrow, which means that the cells do not fully mature before they end up in the blood. “It is like sending untrained soldiers to the front. They are present, but do not really know what to do.” With the cultured skin model, the team can investigate how these inflammatory responses proceed and how drugs can control the inflammation to accelerate healing. This is essential for the development of new treatments.

Improvement of the culture skin model

Mulder points out that the cultured skin model still requires further development. For example, it lacks a circulatory system and nervous system, which means that not all processes that take place in the body during a burn can be imitated. However, the researchers are working on improvements, such as adding nerves, hair follicles and pigment. This not only makes the research more realistic, but also offers significant advantages for patients. “At the moment, the transplanted skin is often still quite bare, without hair, pigment or glands. A skin that comes closer to reality can greatly improve the quality of life of patients.”

Mulder sees a promising future for cultured skin, both clinically and for preclinical research. “Using cultured skin not only saves laboratory animals, but can also improve care in the long term. Fewer complications lead to faster healing, and fewer scars mean fewer reconstruction surgeries. Some burn patients undergo dozens of surgeries in their lives. If we can reduce that, we can really make a difference for the patient.”