Dermal equivalent
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The dermal equivalent, also known as dermal replacement or neodermis, is an ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' model of the dermal layer of skin. There is no specific way of forming a dermal equivalent, however the first dermal equivalent was constructed by seeding dermal
fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
s into a
collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...
gel. This gel may then be allowed to contract as a model of wound contraction. This collagen gel contraction assay may be used to screen for treatments which promote or inhibit contraction and thus affect the development of a
scar A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a ...
. Other cell types may be incorporated into the dermal equivalent to increase the complexity of the model. For example,
keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
may be seeded on the surface to create a skin equivalent, or
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
may be incorporated to model the inflammatory phase of
wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
. A number of commercial dermal equivalents with different compositions and development methods are available. These include Integra, AlloDerm, and Dermagraft, among others.


Purpose

Autotransplantation Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek). The autologous tissue (also called autogenous, autogenei ...
has been common practice for treating individuals who have a need for skin transplants. However, there is the issue of needing repeated grafts or transplants for patients with serious injuries such as burn victims, leading to numerous problems including lack of supply of the skin, preservation, and the possibility if disease transmission. Thus, this prompted for the development of various techniques to create artificial skin, including dermal equivalents. Now, the use of dermal equivalents has expanded from burn wounds to other areas such as various reconstructive surgeries and treatment of chronic wounds.


Risks

There are potential risks when it comes to the application of any dermal equivalent, as there is with any skin grafting or skin substitution technique. These concerns include but are not limited to a negative immune response, possible infection, slow healing, pain, and scarring.


History

The development of artificial skin and dermis began in the 20th century. It was prompted by the discovery of the ability to isolate and culture cells ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'', which was in 1907 by American embryologist Ross Granville Harrison when he was able to isolate and grow embryonic tissues from frogs in his laboratory. In 1975, keratinocytes, which are cells that account for the majority epidermal skin cells, were first isolated and successfully cultured in vitro by James G. Rheinwald and Howard Green. Afterwards, in 1981, bilayer artificial skin or dermal graft was developed by
John F. Burke John F. Burke (July 22, 1922 – 2011) was an American medical researcher at Harvard University widely known for his co-invention of synthetic skin in 1981, together with Dr. Ioannis V. Yannas. ttp://articles.latimes.com/2011/nov/14/health/la- ...
, Ioannis V. Yannas, and other researchers, which was successful in covering “physiologically close to 60% of the body surface.” Burke’s dermal graft was one of the earliest developments of the dermal equivalent, or “neodermis”. Years later, Integra artificial skin, which is now called Integra Dermal Regeneration Template (IDRT) by Integra LifeSciences, was developed from Burke et al.'s innovation. It became the first commercial product approved by the FDA for dermal replacements and listed as one of the "Significant Medical Device Breakthroughs" in 1996.


Commercial products and applications

There are a variety of dermal equivalents from how they are developed and what they are used for. The following three are some of the most commonly reviewed and assessed dermal equivalents.


Integra

The initial research of dermal equivalent leading to the Integra product resulted in a bilayer structure consisting of a dermal portion and epidermal portion. The dermal portion is composed of bovine hide collagen and chondroitin 6-sulfate that is crosslinked with
glutaraldehyde Glutaraldehyde is an organic compound with the formula . The molecule consists of a five carbon chain doubly terminated with formyl (CHO) groups. It is usually used as a solution in water, and such solutions exists as a collection of hydrates, c ...
. The epidermal portion is composed of
Silastic Silastic (a portmanteau of 'silicone' and 'plastic') is a trademark registered in 1948 by Dow Corning Corporation for flexible, inert silicone elastomer. Composition The Silastic trademark refers to silicone elastomers, silicone tubing and some cr ...
covering the dermis. For application, the bilayer structure is placed on the wound after removal of the
eschar An eschar (; Greek: ''ἐσχάρᾱ'', ''eskhara''; Latin: ''eschara'') is a slough or piece of dead tissue that is cast off from the surface of the skin, particularly after a burn injury, but also seen in gangrene, ulcer, fungal infections, ...
and left for several days. Then, the epidermal layer is removed and replaced with artificial epidermis. The dermal equivalent, or neodermis layer, is not removed as it is suitable for growth of cells and vessels. The two layer process, however, may potentially lead to an infection due to any unwanted accumulation between the layers. The main and primary use of Integra was for burn victims who required skin grafts.


Integra Dermal Regeneration Template

Formerly known as Integra artificial skin, Integra Dermal Regeneration Template, or IDRT, was the first FDA approved product for dermal replacements. The Integra Dermal Regeneration Template’s bilayer structure is composed of bovine tendon
collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...
and chondroitin-6-sulfate for the dermal layer, and polysiloxane for the epidermal layer. The polysiloxane epidermal layer is semipermeable, allowing for the controlled water vapor loss, flexible anti-bacterial support of the wound, and mechanical strength for the dermal equivalent. The dermal layer scaffold promotes vascularization and generation of a neodermis. Similar to its predecessor, the method of application is the same. IDRT has low risks of immunogenic response, as well as low disease transmission.


AlloDerm

AlloDerm is the first type of acellular dermal matrix (ADM) derived from the skin of
cadaver A cadaver or corpse is a dead human body that is used by medical students, physicians and other scientists to study anatomy, identify disease sites, determine causes of death, and provide tissue to repair a defect in a living human being. Stud ...
s from the collagen fiber network after the removal of the epidermal layer of the cadaveric skin. It is widely used in dental surgeries for
gingival grafting Gingival grafting, also called gum grafting or periodontal plastic surgery, is a generic term for the performance of any of a number of periodontal surgical procedures in which the gum tissue is grafted. The aim may be to cover exposed root surf ...
, abdominal hernia repair, oculoplastic and orbital surgeries, and breast surgeries. Due to its acellular structure, there is no immunogenic response caused from the application of AlloDerm.


Dermagraft

Dermagraft is a human
fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
–derived dermal replacement. It is derived from neonatal dermal fibroblasts implanted into a bioabsorbable polyglactin mesh scaffold along with
extracellular matrix proteins In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structu ...
that are secreted by the fibroblasts. It can promote re-epithelization, however, there is a potential for antigenic response. Dermagraft is mainly used for the treatment of chronic wounds such as various ulcers including
diabetic foot ulcer Diabetic foot ulcer is a major complication of diabetes mellitus, and probably the major component of the diabetic foot. Wound healing is an innate mechanism of action that works reliably most of the time. A key feature of wound healing is step ...
s and venous foot ulcers. It received premarket approval from the FDA in 2001 for the treatment of diabetic foot ulcers.


See also

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Tissue engineering Tissue engineering is a biomedical engineering discipline that uses a combination of Cell (biology), cells, engineering, Materials science, materials methods, and suitable biochemistry, biochemical and physicochemical factors to restore, maintai ...
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Artificial skin Artificial skin is a collagen scaffold that induces regeneration of skin in mammals such as humans. The term was used in the late 1970s and early 1980s to describe a new treatment for massive burns. It was later discovered that treatment of deep ski ...
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Regenerative medicine Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...
*
Regeneration in humans Regeneration in humans is the regrowth of lost tissues or organs in response to injury. This is in contrast to wound healing, or partial regeneration, which involves closing up the injury site with some gradation of scar tissue. Some tissues such ...


References

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External links


Integra

AlloDerm

Dermagraft
{{DEFAULTSORT:Dermal Equivalent Skin physiology