Research for regenerative medicine A World without Scars? Unraveling the Riddles of Wound Healing

Whether it is scars after severe burns or scarring of the lungs, as in the still incurable disease pulmonary fibrosis - scar tissue can severely impair life or, in the worst case, even become life threatening. Yuval Rinkevich, head of the Institute for Regenerative Biology and Medicine at Helmholtz Munich, has the goal of unraveling the mysteries of scarring and thus revolutionizing regenerative medicine. How he will do that? - We took a look.

At first glance, it seems like science fiction - animals that can regenerate individual organs or even their entire bodies from just a few cells. In fact, there are quite a few examples of this in nature. Some species have amazing regenerative abilities: Zebrafish can recreate their tail fin when nibbled. If planarians (flatworms) are divided into several parts, a completely new worm can emerge from each one.

Creatures that are more complex, such as mammals, usually do not possess this incredible regenerative ability. Humans in particular usually form a scar when they are injured. The fact that the body forms scars makes perfect sense; they quickly close open wounds and can thus protect against infections of breached tissue/organ surfaces. However, scar tissue is not normal tissue - it is less elastic, for example and scars replace the original tissue foundation, meaning areas that scar do not develop functional tissue thereby reducing tissue/organ functionality and physiologic performance and may ultimately lead to organ failure necessitating organ transplantation. Depending on the size or location of the scar, it can also restrict freedom of movement or even the function of organs.

If it were possible to stimulate scar-free wound healing or even to return scars that have already formed to normal tissue, this could revolutionize medicine. Yuval Rinkevich and his team at Helmholtz Munich are pursuing exactly this goal. The researchers want to understand how scars form so that they can then specifically intervene in the processes of scar formation.

More precisely, however, it is not only about the formation of scars, but rather about how tissues and organs regenerate and which cellular and molecular mechanisms take place during wound healing. To find out, the team uses state-of-the-art approaches from cell and molecular genetics, embryology, developmental and stem cell biology.

Rinkevich's team has already opened up a new view of wound healing and has shown that previous assumptions about wound healing processes are outdated.

It is known that special cells called fibroblasts play an important role in wound healing and scar formation. They migrate to the injury, where they help seal the wound with accumulations of connective tissue called the extracellular matrix. But what tissue do fibroblasts come from in skin injuries?

For a long time it was assumed that, they come from the dermis - the corium. This is incorrect, as Rinkevich's studies show. The fibroblasts come from a much deeper layer - the fascia.

Fascia? The same fascia we work with hard foam rollers or balls to feel more flexible again? Close. The term fascia quite broadly describes the soft components that help stabilize our bodies. Essentially, what a layperson would think of as "connective tissue." Fascia penetrates and surrounds muscles, blood vessels or embeds our internal organs. Moreover, they sit under the skin.

Fibroblasts, which are responsible for healing skin injuries, come from this fascia. And they do not come alone. As Rinkevich's team was also able to show, they bring the gelatinous extracellular matrix that surrounds them right along with them when they migrate to the site of the injury. Including embedded blood vessels, immune cells and nerve fibers. This allows the wound to close quickly.

The more we learn about scarring, the better we can address a plethora of human diseases where scars and fibrosis develop. If we fully understand how scars naturally form, we may be able to manipulate and shut down this process or block it altogether. Our goal is to let wounds heal without scarring. - Yuval Rinkevich

Such a transport of already existing extracellular matrix to the site of the wound also takes place in injuries of internal organs - as shown by further studies by the team. Here, it is cells of the immune system, the neutrophils, which take over this task. But not all matrices are the same - depending on the organ, the composition of the proteins, enzymes, etc. contained therein differs, and this also affects how the wound heals - whether scar-free or not.

Exciting, isn't it? But what are the specific reasons that scars should be completely prevented? We asked Yuval Rinkevich.

Yuval, why should we avoid scars? After all, they are part of the natural healing process after an injury?

Rinkevich: That is true - scars can be lifesavers, because they quickly close open wounds. However, the more serious the scar, the more it can affect us in our daily lives, because scar tissue is not fully functional. If scars develop inside our body, on organs, in the worst case it can even lead to organ failure. One example is the chronic disease pulmonary fibrosis, in which scars form in the small, fine alveoli of the lungs, which can then no longer absorb sufficient oxygen. In such cases, only transplantation can help.

If we could prevent the formation of scars, that would help many patients. Operations could be done with far fewer complications and much faster. It might even be possible to perform operations that are not possible at all today because of the severe scarring.

Do you have an example of that?

Rinkevich: Oh, yes. In our research, for example, we also deal with fibrous adhesions in the abdominal cavity, the so-called abdominal adhesions, which consist of bands of fibrous scar tissue. They usually form after surgery and can cause organs in the abdomen to stick together. This restricts the movement of organs and is, for example, the main cause of infertility in women and complications after surgery. Abdominal surgeries can also be delayed by hours simply because surgeons must first remove adhesions.

Therefore, if there were no scarring, abdominal surgeries could be performed much easier, faster and with less risk! A solution would not only simplify the lives of the patients, but also those of the physicians.

Do you think it would be possible to "undo" existing scars?

Rinkevich: It would be a huge step if it were possible to bring scars back into harmony with the surrounding tissue. For example, we could then help people with severe scarring on their skin to regain their sense of touch. We could also develop new therapeutic approaches for diseases in which the scarring of organs plays a role. For example, cell therapies for chronic lung diseases would be conceivable, such as for the numerous different forms of pulmonary fibrosis, which are incurable up to now.

I hope that one day this will be possible and that we can make a decisive contribution to this with our research!