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The Skin Substitute in Burns Treatment

Application of skin substitute for burns or combustion treatment has been started since the 1980s. Utilization of tissue engineering technology to create skin replacement tissue has succeeded in improving the quality of wound healing in burn cases and provides a good alternative therapy in addition to existing conventional therapies.

The Skin Substitute in Burn Treatment



Problems in Burns Wound Treatment

The principle of burn treatment adopted today is "early excision and skin grafting". Dead skin tissue is excised as soon as possible, and the wound is immediately covered with an autologous skin graft. The purpose of applying this principle is to reduce the impact of systemic inflammation and the risk of infection caused by dead skin tissue. The application of this principle has been reported to reduce mortality and morbidity in burn patients.

Wound management problems are present in patients with extensive burns. The large area that must be covered by the skin graft and the limited available donor area are the main obstacles to applying the principle of "early excision and skin grafting". Tissue engineering technology is the answer to this problem. The researchers try to produce tissue substitutes (skin substitutes) or material that could be used to cover the injured area in these patients.

The ideal skin substitute is material that can provide structural support to the skin has durable properties, the composition that resembles normal tissue, nonimmunogenic, inexpensive, can be used immediately and universally, also has a high rate of therapeutic success. Until now, researchers are still trying to create products that can meet all these criteria.


Skin Substitute as a Result of the Application of Tissue Engineering Technology

In 1975, researchers succeeded in breeding epidermal and dermis cells in vitro. Skin substitutes were used in burn cases for the first time in 1981. Until now, various skin substitute products have been developed and used clinically throughout the world not only for burn cases but also in ulcers and other medical cases where there is a lack of skin tissue.

Based on its components, the skin substitute can be divided into:
a. Epidermal (cultured epidermal autograft or CEA): the main material making up this skin substitute is keratinocytes. This tissue replacement functions as the outer covering of the skin like the epidermis layer.

b. Dermal: This skin substitute product is generally in the form of the extracellular scaffold matrix with ingredients derived from animals, humans, or synthetic materials. In some products, the matrix also contains cells. The functions of dermal skin substitute as structural support for autologous skin grafts or epidermal tissue replacement.

c. Combination (dermo-epidermal): This skin substitute has dermis and epidermis components so that it is expected to be used as a definitive or permanent skin replacement such as skin graft. 


24-year-old male patient with a full-thickness chemical burn (sulfuric acid) to the left upper limb, involving creases. A: Initial appearance, with an adhered and hard eschar; B: formation of a uniform and non-hypertrophic granulation tissue. It was red and had no discharge following two escharotomies. It was covered temporarily with skin allografts; C: placement of split-thickness skin grafts transversely soon after surgery; D: appearance at postoperative month 1


The Skin Substitute Application in Extensive Burn Management

Cultured epidermal autograft (CEA) as a replacement for the epidermis has a poor success rate of the graft (take) when used directly in burn after excision of necrotic skin tissue because CEA requires a dermis tissue base with good vascularity. Therefore, the use of skin substitutes for burn wound cases is generally done in stages and combined with skin originating from cadavers (allograft).

In the first stage, the patient underwent surgery for the excision of necrotic skin tissue. Available healthy skin donors are taken a little to undergo the breeding process. The remaining area of healthy skin available is used as a skin graft donor to seal the burn as optimal as possible. Areas that have not been covered by autologous skin grafts are covered by using allograft or the dermal skin substitute. To get an adequate amount of CEA, it takes about 2-3 weeks to breed.

In the second stage, the epidermis of an allograft is removed, so that remains is the allograft dermis that has been appropriately vascularized and filled by migrating fibroblasts. The same process also occurs in the use of dermal skin substitute. Furthermore, the CEA that has been produced or the autologous skin graft can be used to cover the area. At this stage, the skin graft donor area used in the first stage of surgery is generally covered with epithelium so that it can be reused as a skin graft donor area. CEA can be applied in the form of sheets or cell suspension spray.

To simplify the use of this skin substitute, researchers tried to create a combination of skin substitutes that already have epidermal and dermis components, so that wound closure can be done in 1 stage. This skin substitute contains autologous keratinocytes and extracellular matrixes with autologous fibroblasts. The disadvantage of the product currently available is longer breeding time, around 30 days. This is certainly a significant obstacle in patients with extensive burns that require rapid wound closure. 


Challenges in Using The Skin Substitute.

Several challenges must be faced in applying the skin substitute in burn management. This technology has been around for almost 40 years. However, the high cost and unavailability of the cadaveric allograft are major obstacles. The Skin substitute also has other disadvantages, which is more fragile and susceptible to infection when compared to natural skin graft tissue. Therefore, handling of skin substitutes must be done very carefully. Also, bedsores must be adequately prepared so as not to experience infections. Preparation of this wound bed must be done with careful planning so that the wound is in a state of 'ready' when the tissue culture is complete. Another disadvantage of the skin substitute product which is available today is doesn't have a completely healthy skin structure. Important histological structures that are not present in the skin substitute include sebaceous glands, sweat glands, melanin pigments, and hair follicles. One effort being developed at this time to overcome these deficiencies is to utilize stem cell technology. Most stem cell research in burn shows good wound healing results in animals and human subjects. The stem cell is expected to stimulate tissue regeneration so that these important structures can be formed again. Another method being studied is to induce stem cells to develop into these important structures. 


Conclusion

The Skin substitute is a tissue engineering technology that is very useful in the treatment of burn cases, especially patients with extensive burns. Currently available are various skin substitute products that can be used in burn cases such as epidermal, dermal, and combination skin substitutes.

The Skin substitute has several weaknesses, namely more fragile and susceptible to infection, and have no important skin structures such as sebaceous glands, sweat glands, melanin pigments, and hair follicles. Various studies that are currently underway, some of which are in the field of stem cells, aiming to overcome these weaknesses and improve the quality of future burn healing.



1. Singer AJ, Boyce ST. Burn wound healing and tissue engineering. J Burn Care Res. 2017;38(3):e605–13.
2. Biedermann T, Boettcher-Haberzeth S, Reichmann E. Tissue engineering of skin for wound coverage. Eur J Pediatr Surg. 2013;23(5):375–82.
3. Chua AWC, Khoo YC, Tan BK, Tan KC, Foo CL, Chong SJ. Skin tissue engineering advances in severe burns: review and therapeutic applications. Burn Trauma. 2016;4(1):1–14.
4. Zhang C, Chen Y, Fu X. Sweat gland regeneration after burn injury: Is stem cell therapy a new hope? Cytotherapy. 2015;17(5):526–35.
5. Ghieh F, Jurjus R, Ibrahim A, Geagea AG, Daouk H, El Baba B, et al. The Use of Stem Cells in Burn Wound Healing: A Review. Biomed Res Int. 2015;2015.


Source: 
1. https://www.alomedika.com  written by dr. Johannes AB, SpBP-RE (Cosmetic and plastic surgery)
2. Picture: http://burnssurgery.blogspot.com/2012/08/thermal-burns-hand-burns-bilateral-feet.html
3. Picture: https://parjournal.net/article/view/2841

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