How hard do humans work to repair their own "natural leather clothes"? Is "fish skin bandage" a savior for burns?

Torn clothes can be mended, but what about skin burns? In recent years, scientists have developed artificial skin, tilapia skin and other treatments. Are these therapies expected to replace traditional skin grafting?

Written by reporter Wang Xueying, Photo and text editor: Ding Lin

New Media Editor/Chen Xuanzhi

Interview experts

Cao Weihong (Chief Physician of Burn and Plastic Surgery Department, Air Force General Hospital of the Chinese People's Liberation Army)

Chen Zhengli (Deputy Chief Physician of Burn Surgery, Changhai Hospital Affiliated to Naval Medical University)

As the saying goes, "A man lives by his face, a tree lives by its skin." It is hard to find a rival in the animal world for humans' concern for their appearance. However, if you lose your skin, you can still find a way to make up for it. Can you easily repair the damaged dermis? The answer from dermatologists is: not necessarily.

According to statistics from the World Health Organization, at least 180,000 people die from burns every year, with the hardest hit being in low- and middle-income countries such as Africa and Southeast Asia. In India, more than one million people suffer from severe burns every year, while in Egypt, Pakistan and other regions, the proportion of children who are burned and eventually suffer varying degrees of lifelong disability is as high as an astonishing 18%.

The health sector needs to invest huge funds to treat burn patients. In 2000, the direct investment of US medical institutions in treating children's burns was 211 million US dollars; in 2007, Norway, whose population is only one-sixtieth of that of the United States, invested as much as 12.7 million US dollars in hospital burn care alone. It can be said that this level of investment is a heavy burden for many developing countries.

On the other hand, even if we put aside economic concerns, burn treatment is not a simple matter. In addition to facing a series of problems such as "scarcity of allogeneic skin sources" and "high postoperative risks" during treatment, patients also have to endure tremendous physical pain - in some traditional treatments, doctors need to use gauze to apply silver-containing burn ointment to the patient's wound to prevent postoperative infection. However, since the wound needs to be frequently changed, and each change almost opens up the healing new skin, the pain caused by the treatment is unspeakable.

▲Due to lack of safety awareness, children are at higher risk of accidental burns and scalds at home (Picture from the Internet)

Therefore, in order to maintain this natural barrier on the body, humans began to explore new "skin".

Artificial skin is expensive

For burn patients, insufficient skin sources may be the number one problem they face during treatment. Theoretically, when the amount of skin loss exceeds 30% of the body surface area, the patient does not have enough autologous skin sources to cover the exposed wound surface. In this case, people naturally think, can we "borrow" a few pieces of skin from other places for emergency use?

Of course you can, but there are certain risks in doing so.

To this day, allogeneic (human) skin is recognized as the best alternative covering for autologous skin. However, "other people's skin" is not so easy to obtain. All over the world, there is a general shortage of skin sources from donors. Especially in developing countries, allogeneic (human) skin sources are always in short supply. Take Brazil as an example. There are only three formal institutions in the country that can provide allogeneic skin sources, and the skin sources can only meet less than 1% of the country's allogeneic skin source demand. On the other hand, although allogeneic skin will undergo a series of treatments such as disinfection, allogeneic skin transplantation still has certain health risks, which may cause patients to be infected with diseases such as hepatitis and AIDS.

In order to fundamentally and completely eliminate these hidden dangers, scientists have come up with the alternative of "artificial skin".

In 1996, Intergra, an American company, developed a new artificial skin by imitating natural skin. This skin, like real human skin, is composed of the epidermis and dermis: the silicon-containing epidermis can not only effectively lock in moisture and prevent bacterial infection, but also gradually separate from the dermis as the patient's wound recovers. This transparent "skin" also makes it convenient for doctors to check the patient's wound at any time; the dermis of Intergra artificial skin is based on collagen and supported by reticular fibers, which can not only help the human body repair itself, but also be absorbed by the body after the new dermis is formed. It can be said that although artificial skin is not completely equivalent to the patient's own skin in terms of technology, it is undoubtedly a better solution for dealing with larger wounds and more serious burns.

▲Integra artificial skin material (Image source: mit.edu)

Even though artificial skin has all the advantages mentioned above, due to its complex structure and cumbersome production, its cost is in an embarrassingly high position and it cannot be commercialized - the cost of cultivating and producing artificial skin in the laboratory is about US$139 per square centimeter.

Since the end of the last century, as more and more companies have emerged that focus on developing technologies to replace and repair human dermis tissue, the price of artificial skin has been greatly reduced, even down to $15 per square centimeter. Even so, for most burn patients living in developing countries, artificial skin is still an unattainable luxury.

Chen Zhengli, deputy chief physician of the Department of Burn Surgery at Changhai Hospital affiliated to the Naval Medical University, pointed out that the public should avoid deifying artificial skin. "Some people think that after using artificial skin, they don't need to take their own skin. In fact, artificial skin is an artificial dermal scaffold, which is an inactive biological material." He said: "Its function cannot completely replace normal skin. We still need to transplant our own epidermis at the same time to form a complete skin layer. So I personally think that in addition to the high cost, the scope of application of artificial skin is also a factor that limits its development."

It has become more urgent to find biological dressings that are more cost-effective and can benefit the general public.

The magical uses of a tilapia

Since artificial skin is so expensive, is there any alternative that humans can "borrow" for use?

Of course there are, such as tilapia skin, which is what Edma Maciel, director of the burns department at the Dr. José Flota Institute in Fortaleza, Brazil, chose to use to "reshape" human skin.

As a large-scale public hospital in the area, the research institute has been trying to use tilapia skin to treat burn patients since 2016. In clinical trials, the research team found that compared with gauze and burn cream, using tilapia skin as wound dressing can not only effectively prevent wound infection, but also help patients shorten recovery time; at the same time, tilapia skin has almost no side effects during treatment. Not only do patients not need to change dressings frequently, but even the pain of the wound is significantly reduced after applying the fish skin.

"Human skin and blood vessels contain a lot of type 1 and type 3 collagen, which can help the skin heal quickly. We found that tilapia skin is not only rich in these two collagens, but also has a much higher content than human skin." Dr. Maciel said. Through many years of clinical trials, Maciel has a deeper understanding of the miraculous effects of tilapia skin: "The elasticity and ductility of this fish skin, and even its ability to lock water, are better than human skin, so it has a good ability to adhere to the wound surface, which is very suitable for dressings to help wound healing."

Claudia, 43, has a personal experience of the healing effects of tilapia skin: many years ago, she accidentally knocked over a kettle of boiling water, resulting in a large area of ​​second-degree burns on her arm. After removing the necrotic tissue from her wound, the doctor attached a piece of fish skin to her wound. During the healing period, the doctors regularly checked the adhesion of the fish skin. Less than ten days later, the doctor cut open the fish skin and found that most of Claudia's wounds had basically healed and new skin had grown. To this day, she can't forget the feeling of having the fish skin attached to her wound: "It was cool, very comfortable, and not painful at all."

▲Brazilian doctors wrap sterilized tilapia skin for burned children (Photo source: nbcnews.com)

Fish skin is not the only thing that can heal burns

Is tilapia the first animal to be used for fish farming? Of course not.

Historically, people have tried to use xenogeneic skin to treat burns much earlier than using artificial skin. As early as 1965, the United States reported a case of using pig skin as a temporary biological dressing to treat burns. Before scientists achieved "artificial skin", in order to improve the survival rate of patients, shorten the process of skin function recovery of patients, and improve the treatment experience of patients, people used various xenogeneic skins such as pig skin, sheep skin and even frog skin as research objects, hoping to "borrow" a layer of biological dressing with better cost-effectiveness and higher feasibility from animals.

Compared with these materials, tilapia not only has better burn treatment effects, but also has other advantages. On the one hand, it is relatively easy to breed this fish on a large scale, which can effectively guarantee the skin source and price of fish skin dressings; on the other hand, researchers have found that compared with pig skin, sheepskin, etc., tilapia skin has better adhesion and higher collagen content, and its side effects are also smaller, and it is not easy to cause wound infection, and the threat of spreading potential zoonotic diseases is also smaller. Chinese researchers also published a paper in 2017 stating that tilapia skin is rich in a large amount of marine collagen peptides, which can reduce inflammation of patients' wounds and effectively improve the healing of burn wounds by promoting the formation of granulation tissue and accelerating cell proliferation.

▲Another burn treatment option that has attracted people's interest in recent years is to use a "skin gun" similar to the one in the picture to spray autologous stem cells into the wound to help skin tissue recover (Photo credit: London Science Museum)

However, it is not easy to turn tilapia skin into a dressing that can be easily applied like gauze: First, the fish collected from the fish farm needs to be cleaned in 0.9% saline. After removing the bones and meat, the fish skin is immersed in 100% glycerol for 3 hours for sterilization. The fish skin that has completed the initial sterilization is then sent for more than 20 days of radioactive irradiation sterilization to ensure that the physical properties of the fish skin are not damaged. Finally, after passing the sterility test, the vacuum-sealed fish skin can be stored for up to two years at below -4°C. Even so, at the Dr. José Flota Institute, the price of such a tilapia skin is still cheaper than the silver-containing burn bandage.

Pig skin or fish skin?

"Using fish skin as a biological dressing can indeed play a protective role. But it is not widely used in China at present," said Dr. Cao Weihong, chief physician of burn and plastic surgery at the General Hospital of the Chinese People's Liberation Army Air Force, in an interview with our reporter. In his opinion, Brazil and other countries' attempts to use tilapia skin to treat burns are largely limited by their own national conditions, and even a "helpless choice."

Chen Zhengli also pointed out that the use of tilapia skin for burn treatment has great limitations: "This treatment is technically feasible, and its advantage is that the raw materials are cheap. It is widely used to treat mild burns or scalds."

Chen Zhengli added: "But its disadvantages are also obvious, such as the high requirements for processing and preservation technology, and it is especially not suitable for more serious burns and infected wounds." In his opinion, the reason why tilapia skin has entered the public's field of vision in recent years is that it has a wide range of uses for shallow wounds, such as scalds, abrasions, mild burns and other shallow wounds. He emphasized: "(Tilapia skin) is indeed effective in promoting healing and preventing infection, but it is not suitable for deep wounds and infected wounds. Once necrosis occurs on the skin or there are already a large number of bacteria, this dressing will not only fail to remove dead skin and regenerate new flesh, but will aggravate the infection."

▲After the wildfires in California, the local veterinarian used tilapia skin to treat burns on black bears (Photo source: vice.com)

The most prominent advantage of pig skin over other xenograft skins is that it has a low rejection reaction. "Due to the low rejection reaction (of pig skin), some pediatric burn patients do not need to change dressings frequently, which can reduce the pain and secondary damage caused by dressing changes." Chen Zhengli said, "It should be said that pig skin is a very suitable external dressing for some patients with shallow burns who have relatively high requirements for wound healing."

Since the 1970s, pig skin has been the preferred biological dressing for treating burns in my country. Among them, fresh xenogeneic pig skin, irradiated pig skin and xenogeneic pig decellularized skin grafts are all common choices. Cao Weihong, who has been deeply engaged in burn treatment for many years, believes that the price advantage of tilapia skin in Brazil is not obvious in my country: "Whether from a technical or market application perspective, my country's research in the field of xenogeneic skin sources is actually very mature. Therefore, the price of pig skin will not be too expensive. Moreover, compared to pig skin, the area of ​​fish skin is usually smaller, which is not very practical for treating large-area burns."

References

[1] who.int/news-room/fact-sheets/detail/burns

[2] Qiu Fukui, Liao Wenlun. Research on the application of xenogeneic pig skin in burn treatment, Medical Information, 2011

[3]Heidi Debels, Dermal Matrices and Bioengineered Skin Substitutes: A Critical Review of Current Options

Produced by: Science Central Kitchen

Produced by: Beijing Science and Technology News | Science Plus Client

Reproduction without authorization is prohibited, and offenders will be prosecuted