"Doctor, will this leave a scar? Presumably, this is one of the most concerned issues for many people after trauma and surgery. After all, scars are obviously different from the original skin in appearance, and it is easy to attract people's attention if they are not handled well. Therefore, how to effectively remove scars has always been an important challenge in wound care, and the research recently published in the journal Science provides a realistic possibility of 1 for removing scars.

What happens when we are physically injured? If you want to remove scars, you must first understand how scars come from, and to know where scars come from, you must start from wound healing.

When the integrity of human tissue is destroyed by various external forces (such as cutting and puncture), it will cause trauma. When there is a wound in human tissue, it will start the complex physiological process of wound healing, which involves the interaction and physiological reaction of many cells. Wound healing contract can be divided into three stages:

(1) Inflammation stage: inflammation and scabbing.

When the wound is produced, the cells in the wound will immediately produce various cytokines to cause inflammatory reaction, attracting immune cells to fight against the infection of foreign bacteria. At the same time, due to the rupture of blood vessels in the injured area, platelets will go to the wound to promote thrombosis and seal the wound, thus reducing more damage and infection to the wound.

(2) hyperplasia: granulation tissue is full of wounds.

At this stage, the wound is mainly filled by the growth of granulation tissue.

Granulation tissue is composed of new microvessels, fibroblasts, various immune cells and collagen secreted by fibroblasts. After granulation tissue is covered by new "epidermal cells", that is, after the contact between the wound and the outside world is closed, it will enter the next stage.

After injury, the process of wound healing can be divided into three stages. Pixabay (III) remodeling stage: collagen and fibroblasts form scars.

Although the appearance of the wound has healed at this stage, there is still a lot of work in the granulation tissue inside the wound.

At this time, the microvessels and immune cells in granulation tissue will gradually decrease, and fibroblasts will gradually differentiate into fibroblasts. These effects can make room for collagen secreted by fibroblasts.

Collagen and fibroblasts will also be reconstructed and arranged in the tissue, making the tissue more compact, further narrowing the wound and increasing the ability to resist external forces, and this new tissue is what we call "scar".

There are three stages in wound healing: (a) inflammation, (b) proliferation and (c) remodeling. References 2 Scars have no hair follicles and sweat glands, and their elasticity is not good. The appearance and interior of scar are different from the original tissue.

Take the skin as an example. Normal skin must contain hair follicles, sweat glands and other ancillary organs, but these scars are gone. In addition, because the arrangement of collagen and fibroblasts in scar is different from that in normal skin, the elasticity and strength of scar are not as good as that in normal skin. For example, large-scale scars at joints such as knees and elbows are often difficult to bend.

It should be noted that scars are a natural product of wound healing and cannot be avoided!

Although many small scratches on the skin only hurt the epidermis, they look the same as the original skin after healing, but they still produce scars, but these scars are not very large and obvious to fill the wound, so we will "mistakenly think" that there is no scar. However, when our body has deep wounds such as "dermis", scar tissue will obviously fill the wounds.

Scar-removing products are not really "scar-removing". Therefore, all kinds of scar removal products and methods on the market at present can only make the scar closer to the surrounding skin tissue in appearance, but can't really eliminate the scar! The real scar removal must be carried out at the stage of wound healing, so as not to form scar tissue.

If you want to have no scars, you must properly handle them during the wound healing period! But Wikipedia, as mentioned earlier, wound healing is a rather complicated physiological reaction, and it is not until these years that we deeply understand its molecular mechanism 2. The recent article published by the research team of Stanford University not only reveals the key molecular mechanism behind scar formation, but also provides the possibility of wound healing without leaving scars.

Fibroblasts: the key to scar formation can be seen from the three processes of wound healing, and "fibroblasts" occupy a key position.

Fibroblasts are not only responsible for the formation of granulation tissue, but also secrete a large amount of collagen during wound remodeling, and at the same time differentiate into fibroblasts, which will make scar tissue more compact under the reconstruction of collagen and fibroblasts.

In 20 15 years, the research published by the team showed that two types of fibroblasts would participate in the process of wound healing, namely, those expressing and not expressing Engrailed- 1 (EN- 1) and those from protein:

EPFs, which can express Engrailed- 1, is the main cell for scar formation.

First of all, the research team found that ENFs in mouse wounds will be transformed into EPFs during wound healing, producing more EPFs.

There are both ENFs and EPFs in mouse skin, but in the stage of wound healing, ENFs will be transformed into EPFs. Why did the reference 1 ENFs become EPFs? It is external force! Knowing the source of epf, they want to know what "factor" *** ENFs was converted into epf.

Because one of the functions of fibroblasts in organisms is to feel various mechanical external forces and change the gene expression of cells after feeling external forces to cope with external forces, the research team speculated that:

* * * The factor that transforms ENFs into EPFs in wounds is the "mechanical external force" caused by the change of skin elasticity after injury.

To prove this idea, they purified ENFs and cultured it in three different experimental environments. The results showed that fibroblasts not only felt different mechanical external forces, but also showed different cell behaviors under different external forces:

Enf will not be converted into EPFs under low mechanical force culture (3D hydrogel); Under high mechanical force (TCPS), it will be transformed into EPFs, which can be reversed by mechanical signal blocker (Y-27632). Reference 1 Scientists have obtained similar results in mouse experiments. When pulling force is applied to the wound of mice, the number of epf in the healed wound will increase, and the scar tissue of mice will be thicker, which can also be reversed by mechanical signal blockers.

Cut off the signal! Don't tell the cells that the wound is under pressure. The above experiments prove that mechanical tension can express Engrailed- 1 in fibroblasts and promote scar formation. If the transmission of mechanical tension signal is blocked, can scar formation be prevented?

Along this line of thought, the researchers found a drug named Vitipofen, which was approved by the FDA to treat eye diseases. Vitipofen can block the key proteins used by cells to sense mechanical signals, thus achieving the ability to block the transmission of mechanical signals.

Mouse experiments show that Vitipofen is "very effective" in wound healing!

As mentioned above, scars do not produce skin appendages such as hair follicles and sweat glands, and their elasticity and strength are also poor. However, after adding Vitipofen, the healed wound not only grows hair, but also sweat glands can function normally, and the elasticity and strength are similar to those of normal skin. When observed under a microscope, it is impossible to distinguish the difference between the healed wound and the original skin.

In addition, from the molecular level, the number of epf in the healed wounds without Vitipofin is much higher than that in the healed wounds with Vitipofin, which indicates that Vitipofin can indeed inhibit the expression of Engrailed- 1 in fibroblasts.

Vitipofen can make the healed wound grow hair. Reference 1 Based on the above results, the research team sorted out the molecular mechanisms and factors affecting scar formation:

The large expression of Engrailed- 1 in fibroblasts is the key factor of scar formation. However, the mechanical tension at the wound can * * * express Engrailed- 1 in a large number of fibroblasts. As long as the mechanical tension is inhibited, the expression of Engrailed- 1 can be effectively inhibited, and the wound of mice can be healed without scars.

The research team revealed the molecular pathways and factors that affect scar formation. Reference 1 How to heal without leaving scars? Professor Michael T. Longaker, the chair of the problem research group who has studied for 30 years, is a plastic surgeon. 1987, when Longaker was still practicing in the operating room of fetal surgery, his tutor assigned him an assignment: Why can the wounds on fetal skin heal without leaving scars, but the skin of children and adults can't?

"I thought about this question for a year, then it became four years, and then it became decades. Since then, in order to answer this question, my research has expanded to many other fields. I always wanted to know how the scar was formed! That's what Professor Longaker said.

By studying the results of this article, we can now get a glimpse of the possibility: the skin of the fetus is not as elastic as that of children and adults, so the skin will not produce mechanical tension because of the change of elasticity after injury. Without mechanical external force, the fibroblasts at the fetal wound will naturally not appear Engrailed- 1, so scar-free healing can be achieved.

In the future, it may be rare to have scars! If the findings of this study can be applied to other organizations, it will bring a great breakthrough to medical trauma treatment. After all, the scars of other tissues are "different" from the original tissues. Too many scars will seriously affect the function of tissues and even organs, such as fibrosis of the heart and liver after injury. If scar-free healing can be achieved through this mechanism, it will be the gospel of many patients!

However, before entering clinical trials, more tests are needed in animal experiments, and the research team also said that it has started research in this area.

Perhaps in the future, leaving scars on wounds is the standard process of wound care, and scars are no longer something to hide. It may be cool, and it is rare to have scars!

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